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  • 1.
    Alevronta, Eleftheria
    et al.
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden / Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet, Sweden.
    Lind, Helena
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Al-Abany, Massoud
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden / Department of Hospital Physics, Karolinska University Hospital, Stockholm, Sweden.
    Waldenström, Ann-Charlotte
    Department of Oncology, Clinical Cancer Epidemiology, the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden / Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Caroline
    Department of Radiation Physics, the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden / Department of Oncology, Clinical Cancer Epidemiology, the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Dunberger, Gail
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Mavroidis, Panayotis
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet, Sweden / Department of Medical Physics, Larissa University Hospital, Larissa, Greece.
    Nyberg, Tommy
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Karl-Axel
    Department of Radiation Physics, the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Åvall Lundqvist, Elisabeth
    Department of Gynecologic Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Steineck, Gunnar
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden / Department of Oncology, Clinical Cancer Epidemiology, the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Lind, Bengt K
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet, Sweden.
    Dose-response relationships for an atomized symptom of fecal incontinence after gynecological radiotherapy.2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, 719-26 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future.

    MATERIAL AND METHODS: Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model.

    RESULTS: The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs.

    CONCLUSIONS: In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.

  • 2.
    Alevronta, Eleftheria
    et al.
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    al-Abany, Massoud
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Nyberg, Tommy
    Karolinska Institute, Sweden.
    Lind, Helena
    Karolinska Institute, Sweden.
    Waldenstrom, Ann-Charlotte
    Sahlgrens Acad, Sweden; Sahlgrens University Hospital, Sweden.
    Olsson, Caroline
    Sahlgrens Acad, Sweden; Gothenburg University, Sweden.
    Dunberger, Gail
    Karolinska Institute, Sweden; Ersta Skondal University of Coll, Sweden.
    Bergmark, Karin
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden; Sahlgrens University Hospital, Sweden.
    Steineck, Gunnar
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden.
    Lind, Bengt K.
    Karolinska Institute, Sweden.
    Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 120, no 3, 537-541 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose: To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom absence of vaginal elasticity and how time to follow-up influences this relation. Material and methods: The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patients age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. Results: The dose-response parameters for absence of vaginal elasticity according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL = 39.8, D-50 = 49.7 (47.2-52.4) Gy, gamma(50) =1.40 (1.12-1.70) and LL = 37.4, D-50 = 46.9 (43.5-50.9) Gy, gamma(50) = 1.81 (1.17-2.51) respectively. Conclusions: The proposed model, which describes the influence of time to follow-up on the dose response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom absence of vaginal elasticity increases with time to follow-up, while D-50 decreases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 3.
    Antonsen, Sofie L
    et al.
    Gynecological Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Åvall Lundqvist, Elisabeth
    Department of Gynecologic Oncology, Karolinska University Hospital, Radiumhemmet, Stockholm, Sweden.
    Salvesen, Helga B
    Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
    Auranen, Annika
    Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.
    Salvarsdottir, Anna
    Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
    Høgdall, Claus
    Gynecological Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Subspecialist training in surgical gynecologic oncology in the Nordic countries.2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 8, 917-920 p.Article in journal (Refereed)
    Abstract [en]

    To survey the centers that can provide subspecialty surgical training and education in gynecological oncology in the Nordic countries, we developed an online questionnaire in co-operation with the Nordic Society of Gynecological Oncology. The link to the survey was mailed to 22 Scandinavian gynecological centers in charge of surgical treatment of cancer patients. Twenty (91%) centers participated. Four centers reported to be accredited European subspecialty training centers, a further six were interested in being accredited, and 11 centers were accredited by the respective National Board. Fourteen (74%) centers were interested in being listed for exchange of fellows. Our data show a large Nordic potential and interest in improving the gynecologic oncology standards and can be used to enhance the awareness of gynecologic oncology training in Scandinavia and to facilitate the exchange of fellows between Nordic countries.

  • 4.
    Apellaniz-Ruiz, Maria
    et al.
    Spanish National Cancer Research Centre CNIO, Spain.
    Sanchez-Barroso, Lara
    Spanish National Cancer Research Centre CNIO, Spain.
    Gutierrez-Gutierrez, Gerardo
    Hospital University of Infanta Sofia, Spain.
    Sereno, Maria
    Hospital University of Infanta Sofia, Spain.
    Garcia-Donas, Jesus
    CIOCC, Spain.
    Åvall Lundqvist, Elisabeth
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Brosen, Kim
    University of Southern Denmark, Denmark.
    Bergmann, Troels K.
    University of Southern Denmark, Denmark.
    Rodriguez-Antona, Cristina
    Spanish National Cancer Research Centre CNIO, Spain; ISCIII Centre Biomed Research Rare Disease CIBERER, Spain.
    Letter: Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel-Letter in CLINICAL CANCER RESEARCH, vol 21, issue 13, pp 3092-30932015In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 21, no 13, 3092-3093 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 5.
    Apellániz-Ruiz, Maria
    et al.
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Tejero, Héctor
    Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain.
    Inglada-Pérez, Lucía
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
    Sánchez-Barroso, Lara
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Gutiérrez-Gutiérrez, Gerardo
    Neurology Section, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Calvo, Isabel
    Medical Oncology Department, Hospital Montepríncipe, Madrid, Spain. Medical Oncology Department, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Castelo, Beatriz
    Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
    Redondo, Andrés
    Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
    García-Donás, Jesus
    Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Romero-Laorden, Nuria
    Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Sereno, Maria
    Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Merino, María
    Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Currás-Freixes, Maria
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Montero-Conde, Cristina
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Mancikova, Veronika
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Al-Shahrour, Fatima
    Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain.
    Cascon, Alberto
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
    Robledo, Mercedes
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain .
    Rodriguez-Antona, Cristina
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain .
    Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 5, 1227-1235 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.

    EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/ gene-based analyses were used to compare variant frequencies among neuropathy groups and Cox regression models were used to analyze neuropathy evolution along treatment.

    RESULTS: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low frequency non-synonymous variants in EPHA6 were present exclusively in patients with high neuropathy and all affected the ligand binding domain. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency non-synonymous variant carriers (HR=14.60, 95%CI=2.33-91.62, P=0.0042) and an independent cohort confirmed an increased neuropathy risk (HR=2.07, 95%CI=1.14-3.77, P=0.017). Combining the series gave an estimated 2.50-fold higher risk of neuropathy (95%CI=1.46-4.31; P=9.1x10(-4)).

    CONCLUSION: This first study sequencing EPHA genes revealed that low frequency variants in EPHA6, EPHA5 and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHAs neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs.

    The full text will be freely available from 2018-01-11 18:07
  • 6.
    Avall Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nordström, L
    Sjövall, K
    Eneroth, P
    Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.1989In: European journal of gynaecological oncology, ISSN 0392-2936, Vol. 10, no 6, 395-405 p.Article in journal (Refereed)
    Abstract [en]

    Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

  • 7.
    Avall-Lundqvist, E H
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Gynecologic Oncology, Karolinska Hospital, Stockholm, Sweden.
    Peterson, C O
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Serum cholesterol and apolipoprotein B levels may reflect disease activity in ovarian cancer patients.1996In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 35, no 8, 1007-10 p.Article in journal (Refereed)
    Abstract [en]

    Data in the literature demonstrates increased receptor-mediated uptake of low density lipoprotein (LDL) in many types of malignant cells compared with normal cells. In acute leukemia, an inverse correlation has been demonstrated between disease activity and plasma cholesterol. To explore whether this is true also for ovarian cancer a case-control study was performed. We serially collected blood samples and assayed serum cholesterol and apolipoprotein B (the receptor recognizing moiety of LDL) in 10 patients with ovarian cancer. At diagnosis, the patients had lower mean cholesterol levels compared with 6 healthy women. An increase was found after primary surgery and after successful initial chemotherapy. The 5 patients who are in complete remission after a mean follow-up time of 79 months had higher cholesterol and apolipoprotein B levels at their last visit than at diagnosis. In contrast, a reduction of the two analytes was found in the patients who died from their ovarian cancer 15 to 28 months after diagnosis. The results may open a possibility for targetted chemotherapy in ovarian cancer with LDL as a drug carrier.

  • 8.
    Avall-Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.
    Sjövall, K
    Hansson, L O
    Eneroth, P
    Peri- and postoperative changes in serum levels of four tumor markers and three acute phase reactants in benign and malignant gynecological diseases.1992In: Archives of Gynecology and Obstetrics, ISSN 0932-0067, E-ISSN 1432-0711, Vol. 251, no 2, 69-78 p.Article in journal (Refereed)
    Abstract [en]

    Serum levels of squamous cell carcinoma antigen, carcinoembryonic antigen, CA 125, tissue polypeptide antigen, CRP, alpha 1-antitrypsin and haptoglobin were determined peri- and postoperatively in patients undergoing surgery for benign gynecological disease (n = 18) and postoperatively in women operated for cervical carcinoma (n = 23). The only significant changes seen after premedication, during anesthesia and during surgery were a decrease in serum concentrations of alpha 1-antitrypsin and haptoglobin. We found no postoperative changes in the serum levels of squamous cell carcinoma antigen nor in carcinoembryonic antigen values. However, the latter analyte was influenced by smoking habits. Elevated levels of CA 125 and tissue polypeptide antigen were found in the cancer patients, predominantly within the first 1-3 weeks after surgery. These levels decreased to normal values within 4-6 weeks postoperatively. The median intraindividual coefficients of variation for the tumor markers ranged between 15% and 28% in 30 control women not having surgery. In general, it would seem advisable to wait 6 weeks after surgery before monitoring with CA 125 and TPA is started.

  • 9.
    Bergmark, K
    et al.
    Sektionen för Gynekologisk Onkologi, Radiumhemmet, Karolinska sjukhuset, Stockholm, Sverige. Forskargruppen klinisk cancerepidemiologi, Karolinska Institutet, Stockholm, Sverige..
    Åvall Lundqvist, Elisabeth
    Sektionen för Gynekologisk Onkologi, Radiumhemmet, Karolinska sjukhuset, Stockholm, Sverige..
    Steineck, G
    Forskargruppen klinisk cancerepidemiologi, Karolinska Institutet, Stockholm, Sverige.
    A Swedish study of women treated for cervix cancer. Gynecologic cancer often affects sexuality2000In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, no 46Article in journal (Refereed)
    Abstract [sv]

    Gynecological cancer and its treatments are often associated with physical, psychological and social consequences that affect the woman's and the couple's sexuality. Especially due to their impact on sexuality, physical changes distress the women considerably, and warrant consideration for women of all ages. Women with gynecological cancer ask for information about possible side-effects of the disease and treatment that can affect the sexual function. At follow-up visits these issues can be attended to through information, with specific suggestions including advice about topical estrogen and dilators, to alleviate possible long-term sequelae.

  • 10.
    Bergmark, K
    et al.
    Gynecological Oncology, Department of Oncology-Pathology, Radiumhemmet, Karolinska Institutet, Stockholm, Sweden. Clinical Cancerepidemiology, Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden .
    Åvall-Lundqvist, Elisabeth
    Gynecological Oncology, Department of Oncology-Pathology, Radiumhemmet, Karolinska Institutet, Stockholm, Sweden.
    Dickman, P W
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden .
    Henningsohn, L
    Clinical Cancerepidemiology, Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden . Department of Urology, Huddinge Hospital, Huddinge, Sweden .
    Steineck, G
    Clinical Cancerepidemiology, Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden. Clinical Cancerepidemiology, Stockholm City Council, Stockholm, Sweden .
    Lymphedema and bladder-emptying difficulties after radical hysterectomy for early cervical cancer and among population controls.2006In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 16, no 3, 1130-1139 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to acquire knowledge that can be used to refine radical hysterectomy to improve quality-of-life outcome. Data were collected in 1996-1997 by means of an anonymous postal questionnaire in a follow-up study of two cohorts (patients and population controls). We attempted to enroll all 332 patients with stage IB-IIA cervical cancer registered in 1991-1992 at the seven departments of gynecological oncology in Sweden and 489 population controls. Ninety three (37%) of the 256 women with a history of cervical cancer who answered the questionnaire (77%) were treated with surgery alone. Three-hundred fifty population controls answered the questionnaire (72%). Women treated with radical hysterectomy, as compared with controls, had an 8-fold increase in symptoms indicating lymphedema (25% reported distress due to lymphedema), a nearly 9-fold increase in difficult emptying of the bladder, and a 22-fold increase in the need to strain to initiate bladder evacuation. Ninety percent of the patients were not willing to trade off survival for freedom from symptoms. Avoiding to induce long-term lymphedema or bladder-emptying difficulties would probably improve quality of life after radical hysterectomy (to cure cervical cancer). Few women want to compromise survival to avoid long-term symptoms.

  • 11.
    Bergmark, Karin
    et al.
    Divisions of Gynecological Oncology and Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Division of Gynecological Oncology Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Dickman, Paul W
    Division of Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Henningsohn, Lars
    Division of Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Steineck, Gunar
    Division of Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Vaginal changes and sexuality in women with a history of cervical cancer.1999In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 340, no 18, 1383-1389 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In women with cervical cancer, treatment causes changes in vaginal anatomy and function. The effect of these changes on sexual function and the extent, if any, to which they distress women are not known.

    METHODS: In 1996 and 1997, we attempted to contact 332 women with a history of early-stage cervical cancer (age range, 26 to 80 years) who had been treated in 1991 and 1992 at the seven departments of gynecological oncology in Sweden and 489 women without a history of cancer (controls) to ask them to answer an anonymous questionnaire about vaginal changes and sexual function.

    RESULTS: We received completed questionnaires from 256 of the women with a history of cervical cancer and 350 of the controls. A total of 167 of 247 women with a history of cancer (68 percent) and 236 of 330 controls (72 percent) reported that they had regular vaginal intercourse. Twenty-six percent of the women who had cancer and 11 percent of the controls reported insufficient vaginal lubrication for sexual intercourse, 26 percent of the women who had cancer and 3 percent of the controls reported a short vagina, and 23 percent of the women who had cancer and 4 percent of the controls reported an insufficiently elastic vagina. Twenty-six percent of the women who had cancer reported moderate or much distress due to vaginal changes, as compared with 8 percent of the women in the control group. Dyspareunia was also more common among the women who had cervical cancer. The frequency of orgasms and orgasmic pleasure was similar in the two groups. Among the women who had cervical cancer, the type of treatment received had little if any effect on the prevalence of specific vaginal changes.

    CONCLUSIONS: Women who have been treated for cervical cancer have persistent vaginal changes that compromise sexual activity and result in considerable distress.

  • 12.
    Bergmark, Karin
    et al.
    Department of Oncology, Gynecological Oncology, Clinical Cancer Epidemiology, Karolinska Institutet PO Box 4402 S-102 68 Stockholm Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Oncology, Gynecological Oncology, Karolinska Institutet, Stockholm Sweden.
    Dickman, Paul W
    Department of Oncology, Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Henningsohn, Lars
    Department of Oncology, Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden / Department of Urology, Huddinge Hospital, Stockholm, Sweden.
    Steineck, Gunnar
    Department of Oncology, Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Patient-rating of distressful symptoms after treatment for early cervical cancer.2002In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 81, no 5, 443-450 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: More refined information on sources of symptom-induced distress in a patient population can improve the quality of pretreatment information, make follow-up visits more efficient and guide research priorities in the efforts to modify treatments.

    METHODS: In a population-based epidemiological study covering all of Sweden, data were collected 1996-97 by means of an anonymous postal questionnaire. We attempted to enroll all 332 patients with stage IB-IIA cervical cancer registered in 1991-92 at the seven departments of gynecological oncology in Sweden.

    RESULTS: A total of 256 cases (77%) completed the questionnaire. After surgery, alone or in combination with intracavitary radiotherapy, several symptoms related to sexual dysfunction are the primary sources of symptom-induced distress (reduced orgasm frequency: much distress 23% (surgery alone) and 23% (intracavitary radiotherapy and surgery), respectively, overall intercourse dysfunction: much distress 17% and 20%, respectively, followed by lymphedema (much distress 14% and 14%, respectively). Dyspareunia (much distress 24%) and defecation urgency (much distress 22%) are two leading causes of distress after surgery and external radiotherapy. After treatment with radiotherapy alone, loose stool and dyspareunia were the two most distressful symptoms (much distress 19% each). When a symptom occurs, fecal leakage and reduced orgasm frequency are the two most distressful ones (measured as much distress, 38% each).

    CONCLUSIONS: The observed symptoms are distressful and should, if one focuses on patient satisfaction, be given priority.

  • 13.
    Bergmark, Karin
    et al.
    Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden / Department of Oncology and Pathology, Division of Clinical Cancer Epidemiology , Karolinska Institutet , Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden.
    Dickman, Paul W
    Department of Oncology and Pathology, Division of Clinical Cancer Epidemiology, and Department of Medical Epidemiology and Biostatistics , Karolinska Institutet , Stockholm, Sweden.
    Steineck, Gunnar
    Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden / Department of Urology , Karolinska University Hospital , Huddinge, Sweden.
    Henningsohn, Lars
    Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden.
    Synergy between sexual abuse and cervical cancer in causing sexual dysfunction.2005In: Journal of sex & marital therapy, ISSN 0092-623X, E-ISSN 1521-0715, Vol. 31, no 5, 361-83 p.Article in journal (Refereed)
    Abstract [en]

    Experiencing a sexual abuse creates a life-long traumatic memory. The life-long effect of such abuse on sexuality, well-being, the risk of contracting cervical cancer, or problems after treatment for cervical cancer is not known. A population-based follow-up study in 1996-97 that used an anonymous postal questionnaire for data collection, 256 women with stage IB-IIA cervical cancer registered in 1991-92 in Sweden, and 350 women without cervical cancer frequency matched for age and region of residence, provided information. Among the women with a history of cervical cancer and the control women, 46 (18%) and 50 (15%), respectively, reported a history of sexual abuse. The follow-up was 1-70 years after the sexual abuse. The relative risk (with 95% confidence interval) of decreased well-being was 2.4 (1.1-5.2) among controls and 2.7 (1.1-6.4) among former cervical cancer patients. A history of both sexual abuse and cervical cancer gave a relative risk of 30.0 (7.0-129.0) for superficial dyspareunia. Sexual abuse increased the risk of sexual problems after treatment. The sexually abused cervical cancer patients were generally less willing than other patients to trade off possible maximal survival and forgo parts of the treatment. A history of sexual abuse and cervical cancer are both independent risk factors for sexual dysfunction and decreased well-being, and there may be a large synergy when both factors are combined. Diagnosis and treatment of cervical cancer may be improved by recognition of a sexual abuse history.

  • 14.
    Börjeson, Sussanne
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hursti, T J
    Department of Psychology, Uppsala University, Uppsala, Sweden.
    Peterson, C
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
    Fredikson, M
    Department of Psychology, Uppsala University, Uppsala, Sweden.
    Fürst, C J
    Stockholms Sjukhem, Stockholm, Sweden.
    Avall-Lundqvist, E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Dept. of Gynaecological Oncology, Karolinska Hospital, Stockholm, Sweden.
    Steineck, G
    Clinical Epidemiology, Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
    Similarities and differences in assessing nausea on a verbal category scale and a visual analogue scale.1997In: Cancer Nursing, ISSN 0162-220X, E-ISSN 1538-9804, Vol. 20, no 4, 260-266 p.Article in journal (Refereed)
    Abstract [en]

    The use of verbal category scales in assessing patient symptoms is evolving, but the extent to which reliability and precision are lost in using them as opposed to a visual analogue scale (VAS) remains uncertain. The present study analyzed the concordance between a four-point verbal category scale and a VAS in assessing nausea intensity in patients undergoing chemotherapy. The analysis of a total of 348 simultaneous ratings by 104 women over four cycles revealed good concordance between the scales. The means of the VAS ratings (range 0-100 mm) corresponding to the four verbal categories divided the scale in four almost equally large parts (no nausea = 0.7, mild = 24.8, moderate = 48.3, severe = 75.1). However, the VAS ranges were wide. On an individual level a one-step change in the verbal category was associated with an average change of 20 mm on the VAS. The choice of scale to use should be based on the need in the particular situation. When measuring intensity of nausea in patients, the VAS is a reasonable choice due to its possibly greater ability to detect changes over time. On the group level, findings on a four-point category scale and a VAS on the average seem similar.

  • 15.
    Corvigno, Sara
    et al.
    Karolinska Institute, Sweden.
    Wisman, G. Bea A.
    University of Groningen, Netherlands.
    Mezheyeuski, Artur
    Karolinska Institute, Sweden.
    van der Zee, Ate G. J.
    University of Groningen, Netherlands.
    Nijman, Hans W.
    University of Groningen, Netherlands.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Ostman, Arne
    Karolinska Institute, Sweden.
    Dahlstrand, Hanna
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 14, 18573-18584 p.Article in journal (Refereed)
    Abstract [en]

    Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers alpha-SMA, PDGF beta R and desmin. Images were digitally analyzed to yield "metrics" related to vasculature and stroma features. Intra-case analyses showed that PDGF beta R in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning `-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGF beta R-positive stroma fraction and high PDGF beta FR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGF beta R- and alpha-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGF beta R in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer.

  • 16.
    Dahm-Kähler, Pernilla
    et al.
    Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden. Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Borgfeldt, Christer
    Department of Obstetrics and Gynecology, Skane University Hospital, Lund University, Lund, Sweden.
    Holmberg, Erik
    Regional Cancer Center Western Sweden, Sahlgrenska University Hospital, Gothenburg, Sweden. Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Staf, Christian
    Regional Cancer Center Western Sweden, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Falconer, Henrik
    Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Bjurberg, Maria
    Department of Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stålberg, Karin
    Department of Women's and Children's health Uppsala University, Uppsala, Sweden.
    Högberg, Thomas
    Department of Cancer Epidemiology, Lund University, Lund, Sweden.
    Åvall-Lundqvist, Elisabeth
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).2017In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 144, no 1, 167-173 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin.

    METHODS: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models.

    RESULTS: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy.

    CONCLUSION: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

  • 17.
    Dillner, L
    et al.
    Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
    Zellbi, A
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Gynecologic Oncology, Karolinska Hospital, Stockholm, Sweden.
    Heino, P
    Eklund, C
    Pettersson, C A
    Forslund, O
    Hansson, B G
    Grandien, M
    Bistoletti, P
    Association of serum antibodies against defined epitopes of human papillomavirus L1, E2, and E7 antigens and of HPV DNA with incident cervical cancer.1995In: Cancer Detection and Prevention, ISSN 0361-090X, E-ISSN 1873-443X, Vol. 19, no 5, 381-93 p.Article in journal (Refereed)
    Abstract [en]

    In order to provide a large-scale evaluation of the association with cervical cancer of antibodies against human papillomavirus (HPV) antigens, sera from 233 patients with primary, untreated cervical cancer and from 157 healthy age- and sex-matched blood donors were analyzed for IgG and IgA antibodies against HPV-derived peptide antigens and against bovine papillomavirus. Several serological responses were strongly associated with cervical cancer, notably the IgG response against the HPV 16 epitopes L1:13 (Relative risk [RR]: 5.3), E2:9 (RR: 2.9), and E7:5 (RR: 4.3), and the IgA response against an HPV 18 E2-derived antigen (245:18, RR: 3.1). HPV DNA in corresponding cervical tumors was analyzed by Southern blotting (SB) and polymerase chain reaction (PCR) in 47 patients. Sixty-six percent of the patients carried HPV DNA as determined by SB, 91% of patients analyzed by PCR. Neither the antibody responses, nor the presence of HPV DNA were significantly associated with the biological properties of the tumors.

  • 18.
    du Bois, A
    et al.
    Department of Gynecology & Gynecologic Oncology, Wiesbaden, Germany..
    Quinn, M
    Thigpen, T
    Vermorken, J
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bookman, M
    Bowtell, D
    Brady, M
    Casado, A
    Cervantes, A
    Eisenhauer, E
    Friedlaender, M
    Fujiwara, K
    Grenman, S
    Guastalla, J P
    Harper, P
    Hogberg, T
    Kaye, S
    Kitchener, H
    Kristensen, G
    Mannel, R
    Meier, W
    Miller, B
    Neijt, J P
    Oza, A
    Ozols, R
    Parmar, M
    Pecorelli, S
    Pfisterer, J
    Poveda, A
    Provencher, D
    Pujade-Lauraine, E
    Randall, M
    Rochon, J
    Rustin, G
    Sagae, S
    Stehman, F
    Stuart, G
    Trimble, E
    Vasey, P
    Vergote, I
    Verheijen, R
    Wagner, U
    2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004).2005In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 16, no 8, viii7-viii12 p.Article in journal (Refereed)
  • 19. du Bois, Andreas
    et al.
    Herrstedt, Jørn
    Hardy-Bessard, Anne-Claire
    Müller, Hans-Helge
    Harter, Philipp
    Kristensen, Gunnar
    Joly, Florence
    Huober, Jens
    Åvall-Lundqvist, Elisabeth
    Karolinska University Hospital, Stockholm, Sweden.
    Weber, Béatrice
    Kurzeder, Christian
    Jelic, Svetislav
    Pujade-Lauraine, Eric
    Burges, Alexander
    Pfisterer, Jacobus
    Gropp, Martina
    Staehle, Anne
    Wimberger, Pauline
    Jackisch, Christian
    Sehouli, Jalid
    Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer.2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 27, 4162-4169 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.

    PATIENTS AND METHODS: We performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m(2), respectively) with the same combination and additional gemcitabine 800 mg/m(2) on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.

    RESULTS: Between 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).

    CONCLUSION: The addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.

  • 20.
    Dunberger, Gail
    et al.
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Lind, Helena
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Steineck, Gunnar
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden / Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Waldenström, Ann-Charlotte
    Department of Gynecological Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nyberg, Tommy
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    al-Abany, Massoud
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Ullakarin
    Department of Clinical Neuroscience, Section of Psychiatry, St Gorans Hospital, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Gynecological Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Fecal incontinence affecting quality of life and social functioning among long-term gynecological cancer survivors.2010In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 20, no 3, 449-460 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Fecal incontinence is a symptom reported by cancer survivors after pelvic radiotherapy and is recognized to be one of the most troubling symptom-induced sources of distress to patients.

    OBJECTIVE: To investigate how fecal incontinence, patient-reported as emptying of all stools into clothing without forewarning, impact self-assessed quality of life from a social, psychological, sexual, and functional aspect among gynecological cancer survivors treated with pelvic radiotherapy.

    METHODS: We identified a cohort of 789 eligible women in the Stockholm and Gothenburg areas treated with pelvic radiotherapy alone or as combined treatment of gynecological cancer. From the Swedish Population Registry, we identified 478 control women. Data were collected using a study-specific, validated, postal questionnaire including questions covering symptoms from the pelvic region, demographics, social functioning, psychological, and quality-of-life issues.

    RESULTS: Participation was 78% for cancer survivors and 72% for control women. The fecal incontinence symptom emptying of all stools into clothing without forewarning was reported by 70 cancer survivors (12%), with lowered quality of life in 74% of the 70 cancer survivors. This symptom kept the survivors from going to parties (relative risk [RR], 11.8; 95% confidence interval [CI], 6.6-21.1), kept the survivors from traveling (RR, 9.3; 95% CI, 5.3-16.5), affected their work ability (RR, 7.9; 95% CI, 3.8-16.4), hindered their sexual life (RR, 9.2; 95% CI, 4.8-17.6), and changed them as persons (RR, 4.9; 95% CI, 2.9-8.1). The prevalence of the symptom emptying of all stools into clothing without forewarning among control women was 3 (1%) of 344.

    CONCLUSIONS: Among gynecological cancer survivors having undergone pelvic radiotherapy alone or as part of a combined treatment, fecal incontinence is associated with social, psychological, sexual, and functional consequences.

  • 21.
    Dunberger, Gail
    et al.
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Lind, Helena
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Steineck, Gunnar
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden / Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Waldenström, Ann-Charlotte
    Department of Gynecological Oncology, Sahlgrenska University Hospital, Gothenburg, Swede.
    Onelöv, Erik
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Gynecological Oncology, Karolinska University Hospital, Stockholm, Sweden .
    Loose stools lead to fecal incontinence among gynecological cancer survivors.2011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 2, 233-242 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Many patients treated with radiotherapy to the pelvic region report a change in bowel habits. Loose stools, urgency and fecal incontinence may have a significant impact on daily life and social functioning.

    MATERIAL AND METHODS: We attempted to follow up 789 women, treated with pelvic radiotherapy for a gynecological cancer during 1991 to 2003 at two departments of gynecological oncology in Sweden. A control group of 478 women from the Swedish Population Registry was also included. As a preparatory study, we made in-depth interviews with 26 women previously treated for gynecological cancer. Based on their narratives, we constructed a study-specific questionnaire including 351 questions and validated it face-to-face. The questionnaire covered questions of physical symptoms originating in the pelvis, demographics, psychological and quality of life factors. In relation to bowel symptoms, 60 questions were asked.

    RESULTS: Six-hundred and sixteen (78%) gynecological cancer survivors and 344 (72%) control women participated. Two-hundred and twenty-six (37%) cancer survivors reported loose stools at least once a week. Eighty-three percent of the survivors with loose stools every day reported defecation urgency with fecal leakage, compared to 20% of cancer survivors without loose stools. Cancer survivors with loose stools at least once a week were 7.7 times more likely to suffer from defecation urgency with fecal leakage (95% CI 4.4-13.3) compared to those who had loose stools once a month or less. In order to avoid loose stools affected survivors with loose stools often skipped meals (13%), made an active choice of food (47%) and preferentially used prescribed medication (36%).

    DISCUSSION: There is a relation between loose stools and defecation urgency with fecal leakage among long-term gynecological cancer survivors treated with pelvic radiotherapy. Targeting loose stools can possibly help survivors to decrease frequency of fecal leakage.

  • 22.
    Dunberger, Gail
    et al.
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Lindquist, Helene
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Waldenström, Ann-Charlotte
    Department of Gynecological Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nyberg, Tommy
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Steineck, Gunnar
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden / Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Gynecological Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Lower limb lymphedema in gynecological cancer survivors--effect on daily life functioning.2013In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 21, no 11, 3063-3070 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Lower limb lymphedema (LLL) is a common condition after pelvic cancer treatment but few studies have evaluated its effect on the quality of life and its consequences on daily life activities among gynecological cancer survivors.

    METHODS: We identified a cohort of 789 eligible women, treated with pelvic radiotherapy alone or as part of combined treatment of gynecological cancer, from 1991 to 2003 at two departments of gynecological oncology in Sweden. As a preparatory study, we conducted in-depth interviews with gynecological cancer survivors and constructed a study-specific questionnaire which we validated face-to-face. The questionnaire covered physical symptoms originating in the pelvis, demographic, psychological, and quality of life factors. In relation to the lymph system, 19 questions were asked.

    RESULTS: Six hundred sixteen (78 %) gynecological cancer survivors answered the questionnaire and participated in the study. Thirty-six percent (218/606) of the cancer survivors reported LLL. Overall quality of life was significantly lower among cancer survivors with LLL. They were also less satisfied with their sleep, more worried about recurrence of cancer, and more likely to interpret symptoms from the body as recurrence. Cancer survivors reported that LLL kept them from physical activity (45 %) and house work (29 %) and affected their ability to partake in social activities (27 %) or to meet friends (20 %).

    CONCLUSION: Lower limb lymphedema has a negative impact on quality of life among gynecological cancer survivors, affecting sleep and daily life activities, yet only a few seek professional help.

  • 23.
    Dunberger, Gail
    et al.
    Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Thulin, Helena
    Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Waldenström, Ann-Charlotte
    Division of Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Lind, Helena
    Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Henningsohn, Lars
    Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Gynaecological Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Steineck, Gunnar
    Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden / Division of Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Kreicbergs, Ulrika
    Department of Women and Child's Health, Karolinska Institutet, Stockholm, Sweden / Sophiahemmet University College, Stockholm, Sweden.
    Cancer survivors' perception of participation in a long-term follow-up study.2013In: Journal of Medical Ethics, ISSN 0306-6800, E-ISSN 1473-4257, Vol. 39, no 1, 41-45 p.Article in journal (Refereed)
    Abstract [en]

    Every year medical researchers make contact with a large number of cancer survivors with the aim of evaluating cancer treatment. For this reason we decided to investigate how Swedish cancer survivors perceived their participation in research studies focusing on the long-term consequences of being a survivor of gynaecological or urinary bladder cancer. Data were collected by means of two study-specific postal questionnaires, both consisting of questions covering physical symptoms, well-being and the experience of being a cancer survivor. Both questionnaires also included questions evaluating the participants' experience of being research subjects. The questionnaires were developed in close co-operation with cancer survivors. The study population consisted of 1068 cancer survivors. Of these, 95% (n=1003) reported that they thought the study was valuable and 54% (n=559) that they had been positively affected by participating. Four per cent (n=39) expressed that they had been negatively affected by their participation in the study. The vast majority of the cancer survivors thought that participating in their particular study was valuable.

  • 24.
    Friedlander, Michael
    et al.
    ANZGOG, Australia-New Zealand.
    Trimble, Edward
    National Cancer Institute, USA.
    Tinker, Anna
    NCIC-CTG, Canada.
    Alberts, David
    SWOG.
    Åvall-Lundqvist, Elisabeth
    NSGO, Scandinavia.
    Brady, Mark
    GOG.
    Harter, Philipp
    AGO OVAR, Germany.
    Pignata, Sandro
    MITO, Italy.
    Pujade-Lauraine, Eric
    GINECO, France.
    Sehouli, Jalid
    AGO OVAR, Germany.
    Vergote, Ignace
    GINECO, France.
    Beale, Philip
    ANZGOG, Australia-New Zealand.
    Bekkers, Rudd
    DGOG, The Netherlands.
    Calvert, Paula
    ICORG, Ireland.
    Copeland, Lawrence
    SWOG.
    Glasspool, Ros
    ICORG, Ireland.
    Gonzalez-Martin, Antonio
    GEICO, Spain.
    Katsaros, Dionysis
    MANGO, Italy.
    Kim, Jae Won
    KGOG, Korea.
    Miller, Brigitte
    RTOG.
    Provencher, Diane
    GINECO, France.
    Rubinstein, Lawrence
    National Cancer Institute, USA.
    Atri, Mostafa
    ACRIN.
    Zeimet, Alain
    AGO-Au, Austria.
    Bacon, Monica
    Gynecologic Cancer InterGroup.
    Kitchener, Henry
    MRC/NCRI, UK.
    Stuart, Gavin C E
    NCIC-CTG, Canada, on behalf of the Gynecologic Cancer InterGroup.
    Clinical trials in recurrent ovarian cancer.2011In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 21, no 4, 771-775 p.Article, review/survey (Refereed)
    Abstract [en]

    The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

  • 25.
    Glasspool, Rosalind M
    et al.
    Beatson West of Scotland Cancer Centre, Glasgow, UK.
    González Martín, Antonio
    Medical Oncology Department, MD Anderson Cancer Centre, Madrid, Spain.
    Millan, David
    Southern General Hospital, Glasgow, UK.
    Lorusso, Domenica
    Gynecologic Oncology Unit, Fondazione IRCCS National Cancer institute of Milan (MITO), Milan, Italy.
    Åvall-Lundqvist, Elisabeth
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Hurteau, Jean A
    Division of Gynecologic Oncology, NorthShore University Health System, University of Chicago Pritzker School of Medicine, Evanston, IL, USA.
    Davis, Alison
    The Canberra Hospital, Canberra, Australia.
    Hilpert, Felix
    University Hospital of Schleswig-Holstein Campus, Kiel, Germany.
    Kim, Jae-Weon
    Department of Obstectrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
    Alexandre, Jérôme
    edical Oncology, Cochin-Hotel Dieu, Paris Descartes University, Paris, France.
    Ledermann, Jonathan A
    UCL Cancer Institute, London, UK.
    Gynecologic Cancer InterGroup (GCIG) consensus review for squamous cell carcinoma of the ovary.2014In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 24, no 9, S26- p.Article, review/survey (Refereed)
    Abstract [en]

    Squamous cell carcinoma of the ovary is a rare complication of mature cystic teratoma. The epidemiology, pathology, diagnosis, and management of this rare tumor are reviewed. Clinical characteristics, preoperative imaging, and tumor markers may help to predict malignancy preoperatively. Complete cytoreduction should be the aim of surgery. The prognosis for stage 1A disease is good, but for women with advanced or recurrent disease, it is very poor and has not improved in recent years. At present, there are insufficient data to provide clear guidance on the optimal management strategy for advanced disease, and there is a need to gain an understanding of the biology and to develop novel effective therapies. This will require coordinated international collaboration.

  • 26.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Mirghani, Rajaa A
    Karolinska University .
    Rymark, Per
    Västerås Hospital.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska University Hospital.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer2009In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 104, no 2, 130-137 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Thirty-eight patients were treated with paclitaxel and carboplatin. The genotypes of CYP2C8*1B, *1C, *2, *3, *4, *5, *6, *7, *8 and P404A, ABCB1 G2677T/A and C3435T, as well as CYP3A4*1B, were determined by pyrosequencing. Phenotyping of CYP3A4 was performed in vivo with quinine as a probe. The patients were monitored for toxicity and 23 patients underwent a more extensive neurotoxicity evaluation. Patients heterozygous for G/A in position 2677 in ABCB1 had a significantly higher clearance of paclitaxel than most other ABCB1 variants. A lower clearance of paclitaxel was found for patients heterozygous for CYP2C8*3 when stratified according to the ABCB1 G2677T/A genotype. In addition, the CYP3A4 enzyme activity in vivo affected which metabolic pathway was dominant in each patient, but not the total clearance of paclitaxel. The exposure to paclitaxel correlated to the degree of neurotoxicity. Our findings suggest that interindividual variability in paclitaxel pharmacokinetics might be predicted by ABCB1 and CYP2C8 genotypes and provide useful information for individualized chemotherapy.

  • 27.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Mirghani, Rajaa A.
    Rymark, Per
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Pharmacogenetics of Paclitaxel in the Treatment of Ovarian Cancer – a Pilot Study in Preparation of Individualized Chemotherapy2007In: Clinical Cancer Research, ISSN 1078-0432Article in journal (Refereed)
  • 28.
    Hernlund, Emma
    et al.
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
    Hjerpe, Elisabet
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
    Shoshan, Maria
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
    Ovarian carcinoma cells with low levels of beta-F1-ATPase are sensitive to combined platinum and 2-deoxy-D-glucose treatment.2009In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 8, no 7, 1916-1923 p.Article in journal (Refereed)
    Abstract [en]

    We have here examined chemopotentiating effects of glycolysis inhibitor 2-deoxy-d-glucose (DG) in two epithelial ovarian carcinoma (EOC) cell lines and 17 freshly isolated ascitic EOC cell samples, and we identify low expression of the beta-F1-ATPase involved in mitochondrial ATP production as a candidate marker for sensitivity to this strategy. Although in the majority of samples, DG per se did not induce apoptosis, cotreatment with DG potentiated apoptosis and total antiproliferative effects of cisplatin and, to a lesser degree, carboplatin. In the cell lines, combination treatment with DG and cisplatin or carboplatin at noninhibitory concentrations prevented posttreatment regrowth in drug-free medium over a total of 5 days. DG per se allowed complete recuperation in drug-free medium. The more platinum-resistant a cell line was, the more sensitive it was to potentiation by DG and showed higher glucose uptake, DG-sensitive lactate production, and lower beta-F1-ATPase levels. In the ascitic samples, DG reduced the median IC(50) for cisplatin by 68% and, in the most sensitive samples, up to 90%, and DG-mediated potentiation correlated with low expression of beta-F1-ATPase. By contrast, cisplatin sensitivity did not correlate with beta-F1-ATPase levels. The findings validate targeting cancer cell glucose metabolism for potentiating platinum chemotherapy in EOC and indicate that reduced beta-F1-ATPase/oxidative phosphorylation distinguishes cells that are amenable to this strategy.

  • 29.
    Hjerpe, Elisabet
    et al.
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Brage, Suzanne Egyhazi
    Department of Oncologyand Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Frostvik Stolt, Marianne
    Department of Oncologyand Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Hemming
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Shoshan, Maria
    DepartmentDepartment of Oncologyand Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Metabolic markers and HSP60 in chemonaive serous solid ovarian cancer versus ascites.2014In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 24, no 8, 1389-1394 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Metabolic pathway alterations in cancer are thought to be dependent upon tumor type-specific oncogenic activation and local nutrient and oxygen supply during disease progression. In serous ovarian cancer, the typical peritoneal spread of disease is caused by shedding of tumor cells into the abdominal cavity, often along with ascites formation. Not much is known about the metabolic features of these detached serous tumor cells. In this study, we investigate the messenger RNA (mRNA) expression of GAPDH (glycolytic glyceraldehyde 3-phosphate dehydrogenase) and PKM2 (pyruvate kinase isoform M2), ATP5B (mitochondrial β-F1-ATPase), and heat shock protein 60 in matched serous solid tumor and corresponding ascites.

    MATERIALS/METHODS: Fresh samples from solid tumor and corresponding ascites were prospectively collected from 40 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 25 met the study eligibility criteria, that is, stage IIC to IV disease of the serous (24) or endometrioid (1) subtype with solid and ascites specimens containing 50% or more tumor cells and with good quality and quantity mRNA yield. All but 2 patients (92%) had type II disease. GAPDH, PKM2, ATP5B, and HSP60 mRNA expressions were assessed by real-time polymerase chain reaction. For each marker, the mRNA expression in solid tumor was pairwise compared with the corresponding expression in ascites using the Wilcoxon matched pairs signed rank sum test.

    RESULTS: In contrast to our hypothesis, the mRNA expression of analyzed metabolic markers and HSP60 did not significantly differ between matched solid tumor and malignant ascites.

    CONCLUSIONS: Our results indicate that further expression changes in genes related to glycolysis or oxidative phosphorylation are not a prerequisite for serous cancer cell survival after detachment.

  • 30.
    Hjerpe, Elisabet
    et al.
    Department of Oncology, Unit for Gynecologic Oncology, Karolinska University Hospital, SE-17176, Stockholm, Sweden.
    Egyhazi Brage, Suzanne
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, SE-17176, Stockholm, Sweden.
    Carlson, Joseph
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Frostvik Stolt, Marianne
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, SE-17176, Stockholm, Sweden.
    Schedvins, Kjell
    Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
    Johansson, Hemming
    Department of Oncology, Unit for Gynecologic Oncology, Karolinska University Hospital, SE-17176, Stockholm, Sweden.
    Shoshan, Maria
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, SE-17176, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Oncology, Unit for Gynecologic Oncology, Karolinska University Hospital, SE-17176, Stockholm, Sweden.
    Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer.2013In: BMC Clinical Pathology, ISSN 1472-6890, E-ISSN 1472-6890, Vol. 113, no 30Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A deregulated energy metabolism is a hallmark of malignant disease that offers possible future targets for treatment. We investigated the prognostic value of the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and pyruvate kinase type M2 (PKM2), mitochondrial β-F1-ATPase (ATP5B) and the bioenergetic cellular (BEC) index in advanced ovarian cancer.

    METHODS: Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 met the eligibility criteria; stage IIC-IV, serous or endometrioid subtype, specimens containing ≥ 50% tumor cells and patients receiving platinum-based chemotherapy. An adequate amount of mRNA could be extracted in all but one case, with a resultant study population of 56 patients. Eighty-six percent of cases had serous tumors, and 93% were grade 2-3. GAPDH, PKM2 and ATP5B mRNA- and protein expression was assessed by real-time PCR and immunohistochemistry. We estimated the association with platinum-free interval (PFI) and overall survival (OS) by Cox proportional hazards models. Median follow-up was 60 months.

    RESULTS: High GAPDH mRNA levels (HR 2.1, 95% CI 1.0-4.5) and low BEC-index (HR 0.47, 95% CI 0.23-0.95) were both independently associated with shorter PFI. Median PFI for patients with high GAPDH mRNA was 5.0 months compared to 10.1 months for low expression cases (p = 0.031). Similarly, median PFI for patients with low BEC-index based on mRNA was 5.3 months compared to 9.8 months for high BEC-index cases (p = 0.028).

    CONCLUSIONS: High GAPDH or low BEC-index mRNA expression indicate early disease progression in advanced serous ovarian cancer.

  • 31.
    Hjerpe, Elisabet
    et al.
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Egyhazi, Suzanne
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Carlson, Joseph
    athology, Karolinska University Hospital, Stockholm, Sweden.
    Stolt, Marianne Frostvik
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Schedvins, Kjell
    Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
    Johansson, Hemming
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Shoshan, Maria
    Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    HSP60 predicts survival in advanced serous ovarian cancer.2013In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 23, no 3, 448-455 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Heat shock protein 60 (HSP60) plays an essential role in malignant cell survival. We evaluated the prognostic and treatment predictive value of HSP60 in advanced ovarian cancer.

    METHODS: Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 fulfilled the eligibility criteria, that is, International Federation of Gynecology and Obstetrics stage IIC-IV, serous/endometrioid tumors, platinum-based chemotherapy, and specimens with 50% tumor cells or greater. Heat shock protein 60 mRNA and protein expression was determined by real-time polymerase chain reaction and immunohistochemistry. We estimated the association between HSP60 and overall survival (OS) and platinum-free interval (PFI) by Cox proportional hazards models and its relationship with treatment response by Fisher's exact test. Median follow-up was 60 months.

    RESULTS: High HSP60 mRNA expression was associated with shorter OS (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.3-8.5) and PFI (HR, 3.3; 95% CI, 1.5-7.2). Likewise, high HSP60 protein expression was associated with shorter OS (HR, 3.2; 95% CI, 1.5-7.1) and PFI (HR, 2.6; 95% CI, 1.3-5.3). Median survival for patients with high HSP60 protein expression was 31 months compared with 55 months for low expression cases (P = 0.016). The impact on OS and PFI was even stronger in the subgroup of grade 3 serous tumors. All patients with low HSP60 levels responded to first-line chemotherapy.

    CONCLUSION: Heat shock protein 60 may identify groups of advanced serous ovarian cancer with different prognosis and treatment response.

  • 32.
    Hursti, T J
    et al.
    Department of Clinical Neuroscience, Karolinska Institute, S-171 76 Stockholm, Sweden / Department of Clinical Psychology, Uppsala University, Box 1225, S-751 42 Uppsala, Sweden;.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Gynaecological Oncology, Radiumhemmet, S-171 76 Stockholm, Sweden.
    Börjeson, S
    Fredrikson, M
    Department of Clinical Psychology, Uppsala University, Box 1225, S-751 42 Uppsala, Sweden;.
    Fürst, C J
    Steineck, G
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Impact of tumour burden on chemotherapy-induced nausea and vomiting.1996In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 74, no 7, 1114-1119 p.Article in journal (Refereed)
    Abstract [en]

    We investigated how residual tumour burden after cytoreductive surgery was related to the occurrence of acute and delayed nausea and vomiting in 101 ovarian cancer patients receiving their first chemotherapy course. The anti-emetic treatment included ondansetron combined with dexamethasone or placebo. After chemotherapy all patients received ondansetron only for 5 days. Two categories of tumour burden (TB) were formed according to the diameter of the greatest residual tumour (< 2 cm = minimal TB and > or = 2 cm = large TB). Self-reports of nausea and vomiting were obtained for 15 days. Other potential predictor variables were assessed and included in multivariate analyses. Patients with large compared with minimal TB had more delayed emesis, especially on days 2-7. They also had more acute nausea. The aggravating effect associated with large residual TB was more evident in patients > or = 55 years. During the second week after the chemotherapy the occurrence of nausea was higher in patients > or = 55 years than in those < 55 years. This was seen primarily in patients with large residual TB. Predictors for no delayed emesis at all were anti-emetic treatment with dexamethasone, minimal tumour burden, low neuroticism and no history of motion sickness. The increased risk of "persistent' delayed nausea and vomiting seen in older patients with large tumour burden may have important clinical implications and warrants further attention.

  • 33.
    Hursti, Timo J
    et al.
    Uppsala Universitet.
    Börjeson, Sussanne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Hellström, Per M
    Karolinska.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska.
    Stock, Solveig
    Karolinska.
    Steineck, Gunnar
    Karolinska.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Effect of chemotherapy on circulating gastrointestinal hormone levels in ovarian cancer patients: Relationship to nausea and vomiting2005In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, no 6, 654-661 p.Article in journal (Refereed)
    Abstract [en]

    Objective. The introduction of 5-HT3 receptor antagonists greatly reduced the problems associated with nausea and vomiting immediately after cancer chemotherapy. However, delayed nausea and vomiting is still a major problem and the underlying mechanism is obscure. Material and methods. We studied the effect of cisplatin-containing combination chemotherapy in 14 ovarian cancer patients on the levels of gastrin and a panel of other hormones as well as glucose and prostaglandin F2α. Blood samples were obtained once daily in the morning before chemotherapy and for 4 days after chemotherapy. Results. Concentrations of many hormones including gastrin were generally high. A pronounced increase in plasma insulin levels occurred on the day after chemotherapy accompanied by a modest increase in plasma glucose concentrations. Minor increases were observed for gastrin, oxytocin and prostaglandin F2α. In contrast, a transient decrease after chemotherapy was observed for motilin. Plasma cortisol decreased markedly after chemotherapy as expected since betamethasone was given as an antiemetic prophylaxis. Certain trends concerning the relationship between some hormones and nausea and vomiting were noted. A high plasma gastrin concentration before chemotherapy was related to delayed vomiting. Relative day-to-day variability of cholecystokinin tended to correlate positively with delayed nausea, whereas an inverse relationship was observed for gastrin variability. Conclusions. Changes in hormone plasma levels were found but only few could be distinguished as possible mediators of delayed nausea and vomiting. © 2005 Taylor & Francis.

  • 34.
    Högberg, Thomas
    et al.
    Avdelningen för cancerepidemiologi, Skånes universitetssjukhus, Lund.
    Bergfeldt, Kjell
    Regionalt cancercentrum Stockholm–Gotland, Stockholm.
    Borgfeldt, Christer
    Kvinnokliniken, Skånes universitetssjukhus, Lund.
    Holmberg, Erik
    Regionalt cancercentrum Väst, Göteborg.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hopp om förbättring av överlevnad i ovarialcancer2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 50, 2281-3 p.Article in journal (Refereed)
    Abstract [en]

    Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival.

  • 35.
    Joly, Florence
    et al.
    Medical Oncology Department, Clinical Research Department, Centre Francois Baclesse, CHU Cote de Nacre, Inserm "cancer&preventions", University of Basse Normandie, Caen, France.
    McAlpine, Jessica
    Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
    Nout, Remi
    Department of Clinical Oncology, University Medical Center, Leiden, the Netherlands.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Shash, Emad
    ORTC, Brussells, Belgium.
    Friedlander, Michael
    Department of Medical Oncology, The Prince of Wales Hospital, University of New South Wales Clinical School, Sydney, Australia.
    Quality of life and patient-reported outcomes in endometrial cancer clinical trials: a call for action!2014In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 24, no 9, 1693-1699 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is increasing recognition that quality of life (QoL) and patient-reported outcomes (PROs) are of fundamental importance and particularly relevant given the relatively high likelihood of long-term survival in most women with endometrial cancer (EC). However, there has been relatively little research focused on this topic. Our objective was to analyze our current knowledge and identify research questions to be included in the design of next clinical trials.

    METHODS: Analyze and critically assess reported clinical trials in EC that have included QoL and PROs as primary or secondary end points.

    RESULTS: Surgery has a significant impact on physical and functional domains of QoL particularly in the first 6 months after diagnosis. Minimally invasive surgery is associated with less acute morbidity than open procedures and this persists over time. Lymphadenectomy is associated with increased incidence of lymphedema, important late effect. Adjuvant external irradiation may cause gastrointestinal and genitourinary symptoms that impact on physical functioning and which can persist over time. In contrast, vaginal brachytherapy has less toxicity and fewer late effects than external irradiation. The impact of treatment on sexuality has been poorly evaluated in EC survivors. There are few published data on QoL and PROs in patients treated with chemotherapy and the long-term impact has not been addressed. There is no evidence that palliative chemotherapy reduces symptoms and improves QoL. There are very few longitudinal studies on survivorship that is an important concern in EC survivors.

    CONCLUSIONS: Although there have been some studies addressing QoL and PROs in EC, we have identified deficiencies and gaps in our knowledge. Careful consideration of QoL and PROs end points and how to include them in clinical trials will result in a better appreciation of how treatments can impact on patients QoL and lead to conduct interventions to reduce late effects.

  • 36.
    Kjölhede, Preben
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dahm-Kähler, Pernilla
    Kvinnosjukvården, Sahlgrenska universitetssjukhuset, Göteborg.
    Tholander, Bengt
    Onkologiska kliniken, Akademiska sjukhuset, Uppsala.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Individualiserad behandling vid ovarialcancer kan bli möjlig2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 50, 2281-3 p.Article in journal (Refereed)
    Abstract [en]

    Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in developed countries. Several promising steps toward individualized therapy have been taken recently due to increased knowledge of molecular biology. Multidisciplinary conferences for treatment planning and the centralization to tertiary surgical centers improve quality of surgery and survival. The primary treatment of EOC is radical surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel. Bevacizumab added to the chemotherapy and used as maintenance treatment is standard in the primary treatment of patients with residual tumor or inoperable patients. The PARP inhibitor olaparib is recommended as maintenance treatment of women with platinum sensitive relapsed BRCA mutated high-grade serous EOC who have responded to platinum-based chemotherapy. BRCA testing should be offered to women with EOC. In platinum-resistant recurrence addition of bevacizumab to chemotherapy should be considered.

  • 37.
    Kristensen, G B
    et al.
    Department of Gynecologic Oncology, The Norwegian Radium Hospital, Oslo, Norway.
    Vergote, I
    Department of Gynecologic Oncology, U.Z. Gasthuisberg, Leuven, Belgium .
    Stuart, G
    Department of Gynecologic Oncology, Tom Baker Cancer Center, Calgary, Canada .
    Del Campo, J M
    Department of Medical Oncology, Hospital General Vall d'Hebron, Barcelona, Spain .
    Kaern, J
    Department of Gynecologic Oncology, The Norwegian Radium Hospital, Oslo, Norway .
    Lopez, A B
    Department of Gynaecological Oncology, Gateshead Hospital, Gateshead, United Kingdom .
    Eisenhauer, E
    NCI Canada Clinical Trials Group, Kingston, Canada .
    Åvall-Lundquist, Elisabeth
    Department of Gynecologic Oncology, Karolinska Hospital, Stockholm, Sweden .
    Ridderheim, M
    Department of Gynecologic Oncology, Lund University Hospital, Lund, Sweden .
    Havsteen, H
    Department of Oncology, Aarhus University Hospital, Aarhus, Denmark .
    Mirza, M R
    Department of Oncology, Odense University Hospital, Odense, Denmark .
    Scheistroen, M
    Department of Gynecologic Oncology, The Norwegian Radium Hospital, Oslo, Norway .
    Vrdoljak, E
    Department of Oncology, University Hospital, Split, Croatia .
    First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin.2003In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 13, no s2, 172-177 p.Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.

  • 38.
    Leandro-Garcia, Luis J.
    et al.
    Spanish National Cancer Research Centre, Spain .
    Inglada-Perez, Lucia
    Spanish National Cancer Research Centre, Spain .
    Pita, Guillermo
    Spanish National Cancer Research Centre, Spain .
    Hjerpe, Elisabet
    Karolinska University Hospital, Sweden .
    Leskelae, Susanna
    Spanish National Cancer Research Centre, Spain .
    Jara, Carlos
    Fdn Hospital Alcorcon, Spain .
    Mielgo, Xabier
    Fdn Hospital Alcorcon, Spain .
    Gonzalez-Neira, Anna
    Spanish National Cancer Research Centre, Spain .
    Robledo, Mercedes
    Spanish National Cancer Research Centre, Spain .
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska University Hospital, Sweden .
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Rodriguez-Antona, Cristina
    Spanish National Cancer Research Centre, Spain .
    Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy2013In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 50, no 9, 599-605 p.Article in journal (Refereed)
    Abstract [en]

    Background Peripheral neuropathy is the dose limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat solid tumours. This toxicity exhibits great inter-individual variability of unknown origin. The present study aimed to identify genetic variants associated with paclitaxel induced neuropathy via a whole genome approach. less thanbrgreater than less thanbrgreater thanMethods A genome-wide association study (GWAS) was performed in 144 white European patients uniformly treated with paclitaxel/carboplatin and for whom detailed data on neuropathy was available. Per allele single nucleotide polymorphism (SNP) associations were assessed by Cox regression, modelling the cumulative dose of paclitaxel up to the development of grade 2 sensory neuropathy. less thanbrgreater than less thanbrgreater thanResults The strongest evidence of association was observed for the ephrin type A receptor 4 (EPHA4) locus (rs17348202, p=1.0x10(-6)), and EPHA6 and EPHA5 were among the top 25 and 50 hits (rs301927, p=3.4x10(-5) and rs1159057, p=6.8x10(-5)), respectively. A meta-analysis of EPHA5-rs7349683, the top marker for paclitaxel induced neuropathy in a previous GWAS (r(2)=0.79 with rs1159057), gave a hazard ratio (HR) estimate of 1.68 (p=1.4x10(-9)). Meta-analysis of the second hit of this GWAS, XKR4-rs4737264, gave a HR of 1.71 (p=3.1x10(-8)). Imputed SNPs at LIMK2 locus were also strongly associated with this toxicity (HR=2.78, p=2.0x10(-7)). less thanbrgreater than less thanbrgreater thanConclusions This study provides independent support of EPHA5-rs7349683 and XKR4-rs4737264 as the first markers of risk of paclitaxel induced neuropathy. In addition, it suggests that other EPHA genes also involved in axonal guidance and repair following neural injury, as well as LIMK2 locus, may play an important role in the development of this toxicity. The identified SNPs could form the basis for individualised paclitaxel chemotherapy.

  • 39.
    Leandro-Garcia, Luis J
    et al.
    Spanish National Cancer Research Centre, Spain .
    Leskelae, Susanna
    Spanish National Cancer Research Centre, Spain .
    Jara, Carlos
    Fdn Hospital Alcorcon, Spain .
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden .
    Wheeler, Heather E
    University of Chicago, IL 60637 USA .
    Dolan, M Eileen
    University of Chicago, IL 60637 USA .
    Inglada-Perez, Lucia
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Maliszewska, Agnieszka
    Spanish National Cancer Research Centre, Spain .
    de Cubas, Aguirre A
    Spanish National Cancer Research Centre, Spain .
    Comino-Mendez, Inaki
    Spanish National Cancer Research Centre, Spain .
    Mancikova, Veronika
    Spanish National Cancer Research Centre, Spain .
    Cascon, Alberto
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Robledo, Mercedes
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Rodriguez-Antona, Cristina
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Regulatory Polymorphisms in beta-Tubulin IIa Are Associated with Paclitaxel-Induced Peripheral Neuropathy2012In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 18, no 16, 4441-4448 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: Peripheral neuropathy is the dose-limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat several solid tumors such as breast, lung, and ovary. The cytotoxic effect of paclitaxel is mediated through beta-tubulin binding in the cellular microtubules. In this study, we investigated the association between paclitaxel neurotoxicity risk and regulatory genetic variants in beta-tubulin genes. less thanbrgreater than less thanbrgreater thanExperimental Design: We measured variation in gene expression of three beta-tubulin isotypes (I, IVb, and IIa) in lymphocytes from 100 healthy volunteers, sequenced the promoter region to identify polymorphisms putatively influencing gene expression and assessed the transcription rate of the identified variants using luciferase assays. To determine whether the identified regulatory polymorphisms were associated with paclitaxel neurotoxicity, we genotyped them in 214 patients treated with paclitaxel. In addition, paclitaxel-induced cytotoxicity in lymphoblastoid cell lines was compared with beta-tubulin expression as measured by Affymetrix exon array. less thanbrgreater than less thanbrgreater thanResults: We found a 63-fold variation in beta-tubulin IIa gene (TUBB2A) mRNA content and three polymorphisms located at -101, -112, and -157 in TUBB2A promoter correlated with increased mRNA levels. The -101 and -112 variants, in total linkage disequilibrium, conferred TUBB2A increased transcription rate. Furthermore, these variants protected from paclitaxel-induced peripheral neuropathy [HR, 0.62; 95% confidence interval (CI), 0.42-0.93; P = 0.021, multivariable analysis]. In addition, an inverse correlation between TUBB2A and paclitaxel-induced apoptosis (P = 0.001) in lymphoblastoid cell lines further supported that higher TUBB2A gene expression conferred lower paclitaxel sensitivity. less thanbrgreater than less thanbrgreater thanConclusions: This is the first study showing that paclitaxel neuropathy risk is influenced by polymorphisms regulating the expression of a beta-tubulin gene.

  • 40.
    Leitao, Mario M
    et al.
    Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Cheng, Xi
    Fudan University Shanghai Cancer Center, Shanghai, China.
    Hamilton, Anne L
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden / Royal Women's Hospital, Melbourne, Australia / University of Melbourne, Melbourne, Australia.
    Siddiqui, Nadeem A
    Glasgow Royal Infirmary, Gynaecology Administration Block, Glasgow, Scotland.
    Jurgenliemk-Schulz, Ina
    Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
    Mahner, Sven
    Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Kim, Kidong
    Department of Obstetrics & Gynecology, Seoul National University Bundang Hospital, Seoul, Korea.
    Freyer, Gilles
    Service d'Oncologie Medicale, Centre Hospitalier Lyon-Sud, Lyon, France.
    Gynecologic Cancer InterGroup (GCIG) consensus review for vulvovaginal melanomas.2014In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 24, no 9, S117-S122 p.Article, review/survey (Refereed)
    Abstract [en]

    Vulvovaginal melanomas are rare tumors that account for a small fraction of all vulvovaginal cancers. Biologically, they seem to be similar to mucosal and acral melanomas of other sites. There are limited data specific to vulvovaginal melanomas, especially regarding systemic therapies. Most treatment decisions are based on extrapolation from data regarding cutaneous melanomas of other sites. It is reasonable to follow already established guidelines from other professional groups and societies. Outcomes tend to be worse compared with cutaneous melanomas likely because of the later presentation and physical biological characteristics of these tumors.

  • 41.
    Lind, H
    et al.
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Waldenström, A-C
    Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Dunberger, G
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    al-Abany, M
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. Department of Medical Physics, Karolinska University Hospital, Stockholm, Sweden.
    Alevronta, E
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Johansson, K-A
    Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Olsson, C
    Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Nyberg, T
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Wilderäng, U
    Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Steineck, G
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. Department of Gynecologic Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study.2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, no 6, 737-745 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women.

    METHODS: We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records.

    RESULTS: Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms.

    CONCLUSION: Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

  • 42.
    Lind, Helena
    et al.
    Karolinska Institute, Sweden.
    Alevronta, Eleftheria
    Karolinska Institute, Sweden; University of Gothenburg, Sweden.
    Steineck, Gunnar
    Karolinska Institute, Sweden; University of Gothenburg, Sweden.
    Waldenström, Ann-Charlotte
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Nyberg, Tommy
    Karolinska Institute, Sweden.
    Olsson, Caroline
    University of Gothenburg, Sweden.
    Wilderang, Ulrica
    University of Gothenburg, Sweden.
    Dunberger, Gail
    Karolinska Institute, Sweden; Ersta Skondal University of Coll, Sweden.
    al-Abany, Massoud
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Defecation into clothing without forewarning and mean radiation dose to bowel and anal-sphincter among gynecological cancer survivors2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 11, 1285-1293 p.Article in journal (Refereed)
    Abstract [en]

    Background: To analyze the relationship between mean radiation dose to the bowels and the anal-sphincter and occurrence of defecation into clothing without forewarning, a specific and serious fecal incontinence symptom after gynecological radiotherapy. Additional potential risk factors associated with the symptom are explored.Material and methods: Data were collected for 519 eligible gynecological cancer survivors, treated with pelvic radiotherapy, with a median follow-up of 5.8 years, using a study-specific questionnaire and medical records. Correlations between defecation into clothing without forewarning and mean dose to organs at risk; the anal-sphincter region, the rectum, the sigmoid and the small intestines were investigated, also taking other risk factors into account.Results: Twelve percent reported having had the symptom at least once in the preceding six months. Mean dosesamp;gt;50Gy to the anal-sphincter region, the rectum, the sigmoid and the small intestines were related to the occurrence of the symptom. Significantly associated risk factors were deliveries with high birth weight, heart failure and lactose and/or gluten intolerance. After adjusting for these factors, mean dosesamp;gt;50Gy to the anal-sphincter region, the sigmoid and the small intestines remained related to the occurrence of the symptom.Conclusion: Mean doses to the bowels and anal-sphincter region are related to the risk of defecation into clothing without forewarning in long-term gynecological cancer survivors treated with pelvic radiotherapy. Further radiobiological modeling may distinguish which organ(s) contribute most to development of the symptom.

  • 43.
    Lindemann, K
    et al.
    Department of Gynecological Cancer, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
    Christensen, R D
    Department of Medical Statistics, University of Southern Denmark, Odense, Denmark.
    Vergote, I
    Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven, Belgium .
    Stuart, G
    Department of Gynecologic Oncology, University of British Columbia, Vancouver, Canada.
    Izquierdo, M A
    Institute of Oncology, Catalán Hospital, Catalania, Spain.
    Kærn, J
    Department of Gynecological Cancer, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
    Havsteen, H
    Department of Oncology, Herlev University Hospital, Herlev, Denmark.
    Eisenhauer, E
    Department of Oncology, Queen’s University, Kingston, Ontario, Canada.
    Ridderheim, M
    Department of Gynecologic Oncology, Lund University Hospital, Lund, Sweden.
    Lopez, A B
    Department of Gynecologic Oncology, Queen Elizabeth Hospital, Gateshead, UK.
    Hirte, H
    Department of Oncology, Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
    Åvall-Lundquvist, Elisabeth
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Vrdoljak, E
    Department of Oncology, University Hospital, Split, Croatia.
    Green, J
    Department of Oncology, Clatterbridge Hospital, Wirral, UK.
    Kristensen, G B
    Department of Gynecological Cancer, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway / Department of Gynecological Cancer, Institute for Medical Informatics, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
    First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG.2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 10, 2613-2619 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel.

    PATIENTS AND METHODS: We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients).

    RESULTS: Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC.

    CONCLUSION: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.

  • 44.
    Lindemann, Kristina
    et al.
    Oslo University Hospital, Norway; University of Sydney, Australia; Westmead Hospital, Australia.
    Gibbs, Emma
    University of Sydney, Australia.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    dePont Christensen, Rene
    University of Southern Denmark, Denmark.
    Woie, Kathrine
    Haukeland Hospital, Norway.
    Kalling, Marten
    Skåne University Hospital, Sweden.
    Auranen, Annika
    Tampere University Hospital, Finland.
    Grenman, Seija
    Turku University Hospital, Finland; University of Turku, Finland.
    Hoegberg, Thomas
    Skåne University Hospital Lund, Sweden.
    Rosenberg, Per
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Skeie-Jensen, Tone
    Oslo University Hospital, Norway.
    Hjerpe, Elisabet
    University of Southern Denmark, Denmark.
    Dorum, Anne
    Oslo University Hospital, Norway.
    Gebski, Val
    University of Sydney, Australia.
    Kristensen, Gunnar
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist)2017In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, no 4, 455-463 p.Article in journal (Refereed)
    Abstract [en]

    Background: Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Methods: Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m(-2) or four weekly pegylated liposomal doxorubicin 40 mg m(-2)) or tamoxifen 40mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Results: Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0-10.4) compared with 12.7 weeks (95% CI, 9.0-16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16-2.05; log-rank P = 0.003). There was no difference in OS between the treatment arms. Conclusions: Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC.

  • 45.
    Lindemann, Kristina
    et al.
    Oslo University Hospital, Norway .
    Malander, Susanne
    University of Lund Hospital, Sweden .
    Christensen, Rene D.
    University of Southern Denmark, Denmark .
    Mirza, Mansoor R.
    University of Copenhagen Hospital, Denmark .
    Kristensen, Gunnar B.
    Oslo University Hospital, Norway Oslo University Hospital, Norway .
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska University Hospital, Sweden .
    Vergote, Ignace
    University Hospital Leuven, Belgium University Hospital Leuven, Belgium .
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Boman, Karin
    University Hospital, Sweden .
    Nordstrom, Britta
    Karolinska University Hospital, Sweden .
    Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO)2014In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, no 68Article in journal (Refereed)
    Abstract [en]

    Background: We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma. Methods: We performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients. Results: Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated. Conclusion: Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients.

  • 46.
    Lundström, Staffan
    et al.
    Department of Palliative Medicine, Stockholms Sjukhem, Stockholm, Sweden.
    Fürst, Carl Johan
    Department of Palliative Medicine, Stockholms Sjukhem, Stockholm, Sweden.
    Börjeson, Sussanne
    Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
    Steineck, Gunnar
    Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
    Hursti, Timo J.
    Department of Psychology, Uppsala University, Uppsala, Sweden.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Fredrikson, Mats
    Department of Psychology, Uppsala University, Uppsala, Sweden.
    Aspects of delayed chemotherapy-induced nausea: Dexamethasone and adrenal response patterns in patients and healthy volunteers2000In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 8, no 5, 431-434 p.Article in journal (Refereed)
    Abstract [en]

    Delayed chemotherapy-induced nausea is still a clinical problem, and the underlying mechanisms are poorly understood. Previous studies have suggested that corticosteroids are involved, although the mechanisms by which corticosteroids exert their anti-emetic effect are largely unknown. We have previously found impaired control of delayed nausea after injection of dexamethasone. The possibility of differences in the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after injection of dexamethasone was investigated in patients (n = 5) with gynaecological cancer being treated with platinum-based chemotherapy and in healthy female volunteers (n = 10). Urinary free cortisol was used to assess the levels of endogenous cortisol. Results showed that in both patients and controls injections of dexamethasone led to a significant decline in endogenous cortisol levels in 24 h and a subsequent significant recovery in the next 24 h. We conclude that the recovery of the HPA axis is rapid after a single dose of dexamethasone in patients and controls. The absence of an abnormal response pattern in patients makes it probable that the suppression and recovery of the HPA axis after injection of dexamethasone does not influence the corticosteroid-induced rebound effect on delayed platinum-induced nausea.

  • 47.
    McAlpine, Jessica N
    et al.
    Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada.
    Greimel, Elfriede
    Department of Medical Psychology and Psychotherapy, Medical University of Graz, Graz, Austria.
    Brotto, Lori A
    Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada.
    Nout, Remy A
    Department of Clinical Oncology, Leiden UniversityMedical Center, Leiden, the Netherlands.
    Shash, Emad
    EORTC, Brussels, Belgium.
    Åvall-Lundqvist, Elisabeth
    Department of Gynecologic Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Friedlander, Michael L
    Department of Medical Oncology, The Prince of Wales Hospital, University of New South Wales Clinical School, Sydney, Australia.
    Joly, Florence
    Departments of Medical Oncology and Clinical Research, Centre Francois Baclesse, CHU Cote de Nacre, University of Basse Normandie, Caen, France.
    Quality of life research in endometrial cancer: what is needed to advance progress in this disease site? Methodological considerations from the Gynecologic Cancer InterGroup Symptom Benefit Working Group brainstorming session, Leiden 2012.2014In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 24, no 9, 1686-1692 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Quality of life (QoL) in endometrial cancer (EC) is understudied. Incorporation of QoL questionnaires and patient-reported outcomes in clinical trials has been inconsistent, and the tools and interpretation of these measures are unfamiliar to most practitioners. In 2012, the Gynecologic Cancer InterGroup Symptom Benefit Working Group convened for a brainstorming collaborative session to address deficiencies and work toward improving the quality and quantity of QoL research in women with EC.

    METHODS: Through literature review and international expert contributions, we compiled a comprehensive appraisal of current generic and disease site-specific QoL assessment tools, strengths and weaknesses of these measures, assessment of sexual health, statistical considerations, and an exploration of the unique array of histopathologic and clinical factors that may influence QoL outcomes in women with EC.

    RESULTS: This collaborative composition is the first publication specific to EC that addresses methodology in QoL research and the components necessary to achieve high quality QoL data in clinical trials. Future recommendations regarding (1) the incorporation of patient-reported outcomes in all clinical trials in EC, (2) definition of an a priori hypothesis, (3) utilization of validated tools and consideration of new tools corresponding to new therapies or specific symptoms, (4) publication within the same time frame as clinical outcome data, and (5) attempt to correct for disease site-specific potential confounders are presented.

    CONCLUSIONS: Improved understanding of methodology in QoL research and an increased undertaking of EC-specific QoL research in clinical trials are imperative if we are to improve outcomes in women with EC.

  • 48.
    Peterson, Curt
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hursti, T J
    Börjeson, S
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fredrikson, M
    Fürst, C J
    Lomberg, H
    Steineck, G
    Single high-dose dexamethasone improves the effect of ondansetron on acute chemotherapy-induced nausea and vomiting but impairs the control of delayed symptoms.1996In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 4, no 6, 440-446 p.Article in journal (Refereed)
    Abstract [en]

    The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.

  • 49.
    Pujade-Lauraine, Eric
    et al.
    Hôpital Hôtel-Dieu, Paris, France .
    Wagner, Uwe
    Philipps University Marburg, Marburg, Germany.
    Åvall-Lundqvist, Elisabeth
    Karolinska University Hospital, Stockholm, Sweden.
    Gebski, Val
    NHMRC Clinical Trials Centre, Sydney, NSW, Australia.
    Heywood, Mark
    BC Cancer Agency, Vancouver, BC, Canada .
    Vasey, Paul A
    Wesley Medical Centre, Auchenflower, QLD, Australia .
    Volgger, Birgit
    Medical University Innsbruck, Innsbruck, Austria .
    Vergote, Ignace
    University Hospital Leuven, Leuven, Belgium.
    Pignata, Sandro
    Cancer National Institute, Naples, Italy .
    Ferrero, Annamaria
    Gynecological Oncology Institute for Cancer Research and Treatment (IRCC) of Candiolo & AO Ordine Mauriziano, Turin, Italy .
    Sehouli, Jalid
    University Hospital Charité, Berlin, Germany .
    Lortholary, Alain
    Centre Catherine De Sienne, Nantes, France.
    Kristensen, Gunnar
    Norwegian Radium Hospital, Oslo, Norway .
    Jackisch, Christian
    Klinikum Offenbach, Offenbach, Germany .
    Joly, Florence
    CHU-Centre François Baclesse, Caen, France.
    Brown, Chris
    NHMRC Clinical Trials Centre, Sydney, NSW, Australia .
    Le Fur, Nathalie
    ARCAGY-GINECO, Paris, France .
    du Bois, Andreas
    Dr Horst Schmidt Klinik, Wiesbaden, Germany .
    Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse.2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 20, 3323-3329 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).

    PATIENTS AND METHODS: Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m(2)) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m(2)) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.

    RESULTS: Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.

    CONCLUSION: To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

  • 50. Quinn, M
    et al.
    Pfisterer, J
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bookman, M
    Bowtell, D
    Casado, A
    Cervantes, A
    Grenman, S
    Harper, P
    Oza, A
    Pecorelli, S
    Pujade-Lauraine, E
    Trimble, E
    Vasey, P
    Wagner, U
    Integration of new or experimental treatment options and new approaches to clinical trials.2005In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 16, no 8, viii30-viii35 p.Article in journal (Refereed)
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