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  • 1.
    Bagge, Ebba
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Beiron, Ulrica
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Malander, Susanne
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Pattern of endocrine treatment for epithelial ovarian cancer in the Southeast medical region of Sweden: a population-based study2019Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, nr 3, s. 320-325Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim of the study: Endocrine treatment (ET) is an alternative as salvage therapy in epithelial ovarian cancer (EOC) but the usage in routine care is unknown. We evaluated the treatment patterns and outcome of patients receiving ET for EOC in the Southeast medical region in Sweden.Method: Patients were identified through the population-based Southeast Quality Registry for gynaecological cancer. Inclusion criteria were: age 18 years, histologically verified EOC diagnosed 2000-2013, ET for 4 weeks. Coverage compared with the Swedish National Cancer Registry was 100%. Data extracted from medical records was collected by means of a study-specific Case Report Form. Last date of follow-up was February 1st, 2018. All statistics were descriptive.Results: Altogether 248 (18%) of 1414 patients were treated with ET. Most (49%) had received only one, and 34% two previous lines of chemotherapy. Time from last chemotherapy to ET was 4 months, range 0-55months. The reason for initiating ET was tumor progression (66%), chemotherapy related toxicity (29%) and maintenance (4%). Tamoxifen was prescribed in 94% of cases. Best response was partial (amp;lt; 5%) and stable disease (50%). No patient had a complete response. 194 (78%) patients received subsequent chemotherapy, of these 27% had 3-7 lines of chemotherapy. Duration of ET was a median 4 months (range 1-80 months). Median time from ET to subsequent chemotherapy was 5 months (range 0-79). The median overall survival was 45 months (range 9-173).Conclusion: In the Southeast region of Sweden, endocrine treatment for EOC was prescribed inconsistently and in various settings, usually initiated by a rising CA-125 level. Poorer documentation and irregular tumor response assessment were observed for endocrine treatment compared to chemotherapy.

  • 2.
    Bjurberg, Maria
    et al.
    Lund Univ, Sweden.
    Holmberg, Erik
    Reg Canc Ctr West, Sweden; Sahlgrens Acad, Sweden.
    Borgfeldt, Christer
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Floter-Radestad, Angelique
    Karolinska Inst, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Visby Hosp, Sweden.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Marcickiewicz, Janusz
    Reg Canc Ctr West, Sweden; Halland Hosp, Sweden.
    Rosenberg, Per
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Primary treatment patterns and survival of cervical cancer in Sweden: A population-based Swedish Gynecologic Cancer Group Study2019Ingår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 155, nr 2, s. 229-236Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p amp;lt; 0.001). In stage IIA1 74% had CTRL, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p amp;lt; 0.001). Stages III-IVA; amp;lt;40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p amp;lt; 0.001). RS stage IVB 7%. Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy. (C) 2019 Elsevier Inc. All rights reserved.

  • 3.
    Borgfeldt, Christer
    et al.
    Lund Univ, Sweden.
    Holmberg, Erik
    Reg Canc Ctr West, Sweden.
    Marcickiewicz, Janusz
    Halland Hosp, Sweden.
    Stålberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Flöter-Rådestad, Angelique
    Karolinska Univ Hosp, Sweden.
    Bjurberg, Maria
    Lund Univ, Sweden; Lund Univ, Sweden.
    Dahm-Kähler, Pernilla
    Sahlgrens Acad, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Visby Hosp, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Rosenberg, Per
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Högberg, Thomas
    Lund Univ, Sweden.
    Survival in endometrial cancer in relation to minimally invasive surgery or open surgery: a Swedish Gynecologic Cancer Group (SweGCG) study2021Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 21, nr 1, artikel-id 658Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundThe aim of this study was to analyze overall survival in endometrial cancer patients FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy).MethodsA population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses.ResultsIn univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18-1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95-1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival.ConclusionThe minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

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  • 4.
    Dahm-Kahler, Pernilla
    et al.
    Univ Gothenburg, Sweden.
    Holmberg, Erik
    Reg Canc Ctr Western Sweden, Sweden.
    Holtenman, Mikael
    Reg Canc Ctr Western Sweden, Sweden.
    Radestad, Angelique Floter
    Karolinska Inst, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden.
    Hjerpe, Elisabet
    Visby Hosp, Sweden.
    Marcickiewicz, Janusz
    Varbergs Hosp, Sweden.
    Bjurberg, Maria
    Lund Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Rosenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Implementation of National Guidelines increased survival in advanced ovarian cancer: A population-based nationwide SweGCG study2021Ingår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 161, nr 1, s. 244-250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim. The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation. Method. Women with primary epithelial ovarian cancer, FIGO stage IIIC?IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008?2011 and 2013?2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated. Results. In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013?2016 vs. 2008?2011 (EMRR 0.89; 95%CI:0.82?0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95% CI:26.8?32.8) vs. 37.4% (95%CI:33.6?41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8?39.2) to 43 months (95%CI,40.9?46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%,ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19 & ndash;1.47, p < 0.001) for NACT+IDS and 3.00 (95% CI,2.66 & ndash;3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age <= 70 years, and stage IIIC were found to be independent factors for improved RS. Conclusion. Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer. (c) 2021 Published by Elsevier Inc.

  • 5.
    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
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    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
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. 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).2017Ingår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 144, nr 1, s. 167-173Artikel i tidskrift (Refereegranskat)
    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.

  • 6.
    Green, Henrik
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Söderkvist, Peter
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi.
    Rosenberg, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Horvath, G.
    Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    In response [2]2006Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 12, nr 13, s. 4127-4129Övrigt (Övrigt vetenskapligt)
    Abstract [en]

    [No abstract available]

  • 7.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Horvath, György
    Department of Oncology, Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    β-tubulin mutations in ovarian cancer using single strand conformation analysis – risk of false positive results from paraffin embedded tissues2006Ingår i: Cancer Letters, ISSN 0304-3835, Vol. 236, nr 1, s. 148-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations in the β-tubulin gene have been proposed as a resistance mechanism to paclitaxel. We therefore investigated the presence of mutations in the β-tubulin M40 gene in 40 ovarian tumours (16 paraffin-embedded and 24 freshly frozen) selected for good or poor response to chemotherapy with paclitaxel or non-tubulin-affecting regimens. The presence of mutations was investigated using single strand conformation analysis followed by sequencing of the products with altered mobility. No sequence variants in the exons of the β-tubulin M40 gene were detected. Non-reproducible shifts were identified, in eight out of 16 paraffin embedded samples. This may explain some of the previously published discrepancies. In conclusion, sequence variants in the β-tubulin M40 gene are rare and are unlikely to be a clinically relevant explanation of resistance to paclitaxel.

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  • 8.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Rosenberg, Per
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    György, Horvath
    Sahlgrenska universitetssjukhuset, Göteborg.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Letters to the Editor: ABCB1 2677>T/A Genotype and paclitaxel pharmacogenetics in ovarian cancer - Response2006Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 12, nr 13, s. 4127-4129Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

       

  • 9.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Horvath, Grörgy
    Department of Oncology Sahlgrenska Academy at Göteborg University, Gothenburg.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    ABCB1 G1199A polymorphism and ovarian cancer response to paclitaxel2008Ingår i: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 97, nr 6, s. 2045-2048Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    P-glycoprotein (P-gp), encoded by the ABCB1 gene, confers multi-drug resistance to a variety of antineoplastic agents, for example, paclitaxel. Recently, the G1199T/A polymorphism in the ABCB1 gene was shown to be important for the function of P-gp as well as for the resistance to several chemotherapeutic agents in vitro. We analyzed the allelic distribution of the G1199T/A and other polymorphisms in exons 11 and 12 of the ABCB1 gene in ovarian cancer patients treated with paclitaxel and carboplatin in order to evaluate their predictive value in vivo. The SNPs C1236T, G1199T/A, and A1308G were determined using Pyrosequencing in 51 patients with advanced ovarian cancer and correlated to the progression free survival. The G1199T/A SNP was found to affect the progression free survival. Although only two heterozygous (G/A) patients were found their mean progression free survival was only 2 months as compared to 19 months for the wild-type patients. This is in accordance with the higher resistance for the 1199A genetic variant found in vitro. Genotyping of the ABCB1 gene may be important for determining the tumor resistance to paclitaxel and provide useful information for individualized therapy.  

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  • 10.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Horvath, György
    Department of Oncology, Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    mdr-1 single nucleotide polymorphisms in ovarian cancer tissue – G2677T/A correlates with response to paclitaxel chemotherapy2006Ingår i: Clinical Cancer Research, ISSN 1078-0432, Vol. 12, nr 3 pt 1, s. 854-859Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: P-glycoprotein, encoded by the mdr-1 gene, confers multidrug resistance to a variety of antineoplastic agents, e.g., paclitaxel. Recently, different polymorphisms in the mdr-1 gene have been identified and their consequences for the function of P-glycoprotein, as well as for the treatment response to P-glycoprotein substrates, are being clarified. We analyzed the allelic frequencies at polymorphic sites G2677T/A and C3435T in ovarian cancer patients with good or poor response to treatment with paclitaxel in combination with carboplatin in order to evaluate their predictive values.

    Experimental Design: Fifty-three patients were included in the study; 28 of them had been relapse-free for at least 1 year and 25 had progressive disease or relapsed within 12 months. A reference material consisting of 200 individuals was also analyzed. The genotypes of each single nucleotide polymorphism (SNP) were determined using Pyrosequencing.

    Results: The G2677T/A SNP was found to significantly correlate with treatment outcome. The probability of responding to paclitaxel treatment was higher in homozygously mutated patients (T/T or T/A; Fisher's exact test; P < 0.05). The frequency of the T or A alleles was also higher in the group of patients who had a good response (P < 0.05). There was also a dose-dependent influence of the number of mutated alleles on the response to paclitaxel treatment (Χ2 test for linear-by-linear association; P = 0.03). However, the C3435T SNP was not found to correlate to treatment outcome.

    Conclusions: The mdr-1 polymorphism G2677T/A in exon 21 correlates with the paclitaxel response in ovarian cancer and may be important for the function of P-glycoprotein and resistance to paclitaxel and provide useful information for individualized therapy.

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  • 11.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiskt centrum.
    Mirghani, Rajaa A
    Karolinska University .
    Rymark, Per
    Västerås Hospital.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Karolinska University Hospital.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Tekniska högskolan. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiskt centrum.
    Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer2009Ingår i: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 104, nr 2, s. 130-137Artikel i tidskrift (Refereegranskat)
    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.

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  • 12.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Mirghani, Rajaa A.
    Rymark, Per
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Pharmacogenetics of Paclitaxel in the Treatment of Ovarian Cancer – a Pilot Study in Preparation of Individualized Chemotherapy2007Ingår i: Clinical Cancer Research, ISSN 1078-0432Artikel i tidskrift (Refereegranskat)
  • 13.
    Hellman, Kristina
    et al.
    Karolinska Univ Hosp, Sweden.
    Holmberg, Erik
    Reg Canc Ctr West, Sweden; Sahlgrens Acad, Sweden.
    Bjurberg, Maria
    Lund Univ, Sweden.
    Borgfeldt, Christer
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden.
    Radestad, Angelique Floter
    Karolinska Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Visby Hosp, Sweden.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Marcickiewicz, Janusz
    Halland Hosp, Sweden.
    Rosenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Primary treatment and relative survival by stage and age in vulvar squamous cell carcinoma: A population-based SweGCG study2020Ingår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 159, nr 3, s. 663-671Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group. Methods. A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort. Results. Median follow-up time was 41 months. The study population included 657 women; 33% were &gt;= 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women &gt;= 80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women &gt;= 80 years compared with women &lt;60 years was 4.3 (p &lt; 0.001); 4.9 (p &lt; 0.001) for stages I-II and 3.5(p = 0.007) for stage III. Conclusions. In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden ad-hered to guidelines. Areas of improvement include treatment for stage II and for the very old. (C) 2020 Elsevier Inc. All rights reserved.

  • 14.
    Hjerpe, Elisabet
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Staf, Christian
    Sahlgrens Univ Hosp, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Bjurberg, Maria
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Borgfeldt, Christer
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Högberg, Thomas
    Lund Univ, Sweden.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Karolinska Inst, Sweden.
    Lymph node metastases as only qualifier for stage IV serous ovarian cancer confers longer survival than other sites of distant disease - a Swedish Gynecologic Cancer Group (SweGCG) study2018Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 3, s. 331-337Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer.Method: This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009-2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations.Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n=51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n=195) or other/multiple (n=187) distant metastases (p=.0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p=.001) or other/multiple distant sites (HR 2.67, p=.007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p=.245).Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.

  • 15.
    Jonsdottir, Bjorg
    et al.
    Uppsala Univ, Sweden.
    Marcickiewicz, Janusz
    Varbergs Hosp, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden; Lund Univ, Sweden.
    Bjurberg, Maria
    Lund Univ, Sweden.
    Dahm-Kahler, Pernilla
    Univ Gothenburg, Sweden.
    Floter-Radestad, Angelique
    Karolinska Inst, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden.
    Holmberg, Erik
    Reg Canc Ctr Western Sweden, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Rosenberg, Per
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer: A Swedish Gynecologic Cancer Group (SweGCG) study2021Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 100, nr 8, s. 1526-1533Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Deep myometrial invasion (&gt;= 50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice. Material and methods This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I-III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard. Results In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively. Conclusions In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI.

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  • 16.
    Liest, Lisbeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Omran, Ahmed Shaker
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Mikiver, Rasmus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Uppugunduri, Srinivas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    RMI and ROMA are equally effective in discriminating between benign and malignant gynecological tumors: A prospective population-based study2019Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, nr 1, s. 24-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Our primary objective was to test the hypothesis that human epididymal protein 4 (HE4) and risk of ovarian malignancy index outperform the CA 125 and risk of malignancy index tests in categorizing a pelvic mass into high or low risk of malignancy in a Swedish population. Furthermore, cut-off values needed to be defined for HE4 and ROMA in premenopausal and postmenopausal women prior to their introduction to clinical practice. A third objective was to investigate the correlation between HE4 levels in serum and urine. Material and methods Women with a pelvic mass scheduled for surgery were recruited from nine hospitals in south-east Sweden. Preoperative blood samples were taken for analyzing CA125 and HE4 as well as urine samples for analyzing HE4. Results We enrolled a total of 901 women, of whom 784 were evaluable. In the premenopausal and postmenopausal groups, no significant differences were found for sensitivity, positive and negative predictive value, either for RMI vs ROMA or for CA125 vs HE4 using a fixed specificity of 75%. Cut-off values indicating malignancy were established for HE4 and ROMA in premenopausal and postmenopausal women. We found no correlation between HE4 concentration in serum and urine. Conclusions We could not confirm that ROMA had diagnostic superiority over RMI in categorizing women with a pelvic mass into low-risk or high-risk groups for malignancy in a Swedish population. We have defined cut-off values for HE4 and ROMA. The lack of correlation between serum and urine HE4 obviates the introduction of urine HE4 analysis in clinical diagnostics.

  • 17.
    Lindemann, Kristina
    et al.
    Oslo University Hospital, Norway; University of Sydney, Australia; Westmead Hospital, Australia.
    Gibbs, Emma
    University of Sydney, Australia.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. 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, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    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)2017Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, nr 4, s. 455-463Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    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
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Karolinska University Hospital, Sweden .
    Vergote, Ignace
    University Hospital Leuven, Belgium University Hospital Leuven, Belgium .
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    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)2014Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, nr 68Artikel i tidskrift (Refereegranskat)
    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.

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  • 19.
    Marcickiewicz, Janusz
    et al.
    Hallands Hosp Varberg, Sweden; Reg Canc Ctr Western Sweden, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Holmberg, Erik Carl Viktor
    Reg Canc Ctr Western Sweden, Sweden; Univ Gothenburg, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden; Lund Univ, Sweden.
    Bjurberg, Maria
    Lund Univ, Sweden.
    Dahm-Kahler, Pernilla
    Univ Gothenburg, Sweden.
    Floter-Radestad, Angelique
    Karolinska Inst, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Rosenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    The wait time to primary surgery in endometrial cancer - impact on survival and predictive factors: a population-based SweGCG study2022Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 61, nr 1, s. 30-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. Material and methods In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time &gt; 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). Results Out of 7366 women, 5535 waited &gt; 32 d for surgery and 1098 &gt; 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time &gt; 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time &lt; 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. Conclusions Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.

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  • 20.
    Mirza, M. R.
    et al.
    Nordic Soc Gynecol Oncol, Denmark; Copenhagen University Hospital, Denmark.
    Monk, B. J.
    University of Arizona, AZ USA; Creighton University of Phoenix, AZ USA; Arizona Oncology Associates, AZ USA.
    Herrstedt, J.
    University of Southern Denmark, Denmark.
    Oza, A. M.
    University of Toronto, Canada.
    Mahner, S.
    Arbeitsgemeinschaft Gynakol Onkol, Germany; University of Munich, Germany.
    Redondo, A.
    GEICO, Spain; Hospital University of La Paz, Spain.
    Fabbro, M.
    French Investigator Grp Ovarian and Breast Cancer GIN, France; Institute Cancer Montpellier, France.
    Ledermann, J. A.
    UCL, England; UCL, England.
    Lorusso, D.
    Ist Nazl Tumori, Italy.
    Vergote, I.
    Luxembourg Gynecol Oncology Grp, Belgium; University of Leuven, Belgium.
    Ben-Baruch, N. E.
    Kaplan Medical Centre, Israel.
    Marth, C.
    AGO Austria, Austria; Medical University of Innsbruck, Austria.
    Madry, R.
    Central and Eastern European Gynecol Oncology Grp, Poland; Uniwersytet Medical Poznaniu, Poland.
    Christensen, R. D.
    University of Southern Denmark, Denmark.
    Berek, J. S.
    Stanford Comprehens Cancer Institute, CA USA.
    Dorum, A.
    Oslo University Hospital, Norway.
    Tinker, A. V.
    British Columbia Cancer Agency, Canada.
    du Bois, A.
    Kliniken Essen Mitte, Germany.
    Gonzalez-Martin, A.
    GEICO, Spain; MD Anderson Cancer Centre Madrid, Spain.
    Follana, P.
    GINECO, France; Centre Antoine Lacassagne, France.
    Benigno, B.
    Northside Hospital, GA USA.
    Rosenberg, Per
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Gilbert, L.
    McGill University, Canada.
    Rimel, B. J.
    Cedars Sinai Medical Centre, CA USA.
    Buscema, J.
    Arizona Oncology Associates, AZ USA.
    Balser, J. P.
    Veristat, MA USA.
    Agarwal, S.
    Tesaro, MA USA.
    Matulonis, U. A.
    Dana Farber Cancer Institute, MA 02115 USA.
    Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer2016Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, nr 22, s. 2154-2164Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P amp;lt; 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)

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  • 21.
    Pietzner, Klaus
    et al.
    Charite, Germany.
    Vergote, Ignace
    University Hospital Leuven, Belgium; Leuven Cancer Institute, Belgium.
    Santoro, Armando
    Ist Clin Humanitas, Italy.
    Chekerov, Radoslav
    Charite, Germany.
    Marme, Frederik
    University of Frauenklin Heidelberg, Germany.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Martinius, Holger
    Neovu Biotech GmbH, Germany.
    Friccius-Quecke, Hilke
    Neovu Biotech GmbH, Germany.
    Sehouli, Jalid
    Charite, Germany; North Eastern German Soc Gynecol NOGGO, Germany.
    Re-challenge with catumaxomab in patients with malignant ascites: results from the SECIMAS study2014Ingår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, nr 12, s. 308-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Malignant ascites is a common phenomenon in cancer patients. It poses a great challenge to the clinician, because of limited treatment options and strong impairment of the quality of life of the often palliative patients. The SECIMAS study investigated the feasibility of a re-challenge with four catumaxomab intraperitoneal infusions in patients who had already received a first cycle of four infusions in the phase III CASIMAS study, which compared catumaxomab with and without prednisolone premedication. The primary endpoint was the proportion of patients who received at least three catumaxomab infusions. Secondary endpoints included a composite safety score (CSS) summarising the worst grades for the main catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain), safety, efficacy and the occurrence of anti-drug antibodies (ADAs). Eight of nine screened patients received a second catumaxomab cycle. Compliance with a catumaxomab re-challenge was high: all eight patients (100 %) received all four infusions. The median CSS was 3.0 versus 3.4 in CASIMAS. The tolerability profile of the second catumaxomab cycle was comparable to that of the first cycle. Median puncture-free survival (48 days) and overall survival (407 days) were longer than in CASIMAS (35 and 103 days, respectively), although median time to next puncture was shorter (60 vs. 97 days). Of six patients sampled, all were ADA positive at screening and remained ADA positive until the end of the study. The presence of ADAs did not affect catumaxomabs safety or efficacy. The CSS and tolerability profile for catumaxomab in SECIMAS were comparable to those in CASIMAS. The majority of patients benefitted from a second cycle of catumaxomab. A re-challenge seems to be feasible and safe for selected patients with recurrent malignant ascites due to carcinoma after a first cycle of catumaxomab.

  • 22.
    Radestad, Angelique Flöter
    et al.
    Karolinska Institutet, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Acad, Sweden.
    Holmberg, Erik
    Univ Gothenburg, Sweden; Reg Canc Ctr West, Sweden.
    Bjurberg, Maria
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Hellman, Kristina
    Karolinska University Hospital, Sweden.
    Högberg, Thomas
    Lund University, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Marcickiewicz, Janusz
    Halland Hospital, Sweden.
    Rosenberg, Per
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Stålberg, Karin
    Uppsala University, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Borgfeldt, Christer
    Lund University, Sweden.
    Long-term incidence of endometrial cancer after endometrial resection and ablation: A population based Swedish gynecologic cancer group (SweGCG) study2022Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 101, nr 8, s. 923-930Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long-term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately. Material and Methods The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997-2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow-up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow-up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis. Results In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow-up time of 7.1 years (interquartile range 3.1-13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population-based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03-0.53) after EA and 1.27 (95% CI 0.86-1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively. Conclusions There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate.

  • 23.
    Ray-Coquard, I.
    et al.
    GINECO and Medical Oncology Department, Centre Léon Bérard, University Claude Bernard Lyon, Lyon, France.
    Cibula, D.
    AGO and Oncogynecologic Center, Department of Obstetrics and Gynecology, General Faculty Hospital, Charles University of Prague, Prague, Czech Republic.
    Mirza, M.R.
    NSGO and Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
    Reuss, A.
    AGO and Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany.
    Ricci, C.
    MITO and Division of Gynecologic Oncology, Department of Women and Childrens Health and Public Health, Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
    Colombo, N.
    MaNGO and European Institute of Oncology and University of Milan Bicocca, Milan, Italy.
    Koch, H.
    AGO Austria and Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria.
    Goffin, F.
    BGOG and CHU de Liège, University of Liège, Liège, Belgium.
    González-Martin, A.
    GEICO and Medical Oncology Department, Clínica Universidad de Navarra, Madrid, Spain.
    Ottevanger, P.B.
    DGOG and Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, Netherlands.
    Baumann, K.
    AGO and Department of Gynecology, Klinikum der Stadt Ludwigshafen GmbH, Ludwigshafen, Germany.
    Bjørge, L.
    NSGO and Department of Gynecology, Haukeland Universitetssykehus, Bergen, Norway; Center for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
    Lesoin, A.
    GINECO and Department of Gynecologic Cancer and Medical Oncology, Centre Oscar Lambret, Lille, France.
    Burges, A.
    AGO and Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Germany.
    Rosenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Gropp-Meier, M.
    AGO and Department of Gynecology and Obstetrics, Oberschwabenklinik, Krankenhaus St. Elisabeth, Ravensburg, Germany.
    Harrela, M.
    NSGO and Department of Gynoncology and Gynecology and Obstetrics, Kymenlaakso Central Hospital, Kotka, Finland.
    Harter, P.
    AGO and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
    Frenel, J.-S.
    GINECO and Centre René Gauducheau, Institut de Cancerologie de lOuest, Saint Herblain, France.
    Minarik, T.
    NSGO and National Institute of Oncology, Bratislava, Slovakia.
    Pisano, C.
    MITO and Department of Uro-Gynecologic Oncology, Istituto Nazionale per Io Studio e la Cura dei Tumori ‘Fondazione G. Pascale’ IRCCS, Naples, Italy.
    Hasenburg, A.
    AGO and Department of Obstetrics and Gynecology, University Medical Center, Mainz, Germany.
    Merger, M.
    Oncology Medicine, Boehringer Ingelheim International GmbH, Biberach, Germany.
    du, Bois A.
    AGO and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
    Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 2, s. 439-448Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AGO-OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front-line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression-free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2–21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with amp;gt;1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83–1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh-risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75–0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports. © 2019 UICC

  • 24.
    Rosenberg, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Staf, Christian
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden.
    Bjurberg, Maria
    Skane Univ Hosp, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Hellman, Kristina
    Karolinska Inst, Sweden.
    Hjerpe, Elisabet
    Karolinska Inst, Sweden.
    Holmberg, Erik
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Data quality in the Swedish Quality Register of Gynecologic Cancer - a Swedish Gynecologic Cancer Group (SweGCG) study2018Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 3, s. 346-353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC).Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearsons correlation coefficient and Cohens kappa coefficient.Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearsons correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively.Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.

  • 25.
    Sehouli, Jalid
    et al.
    Charite, Germany .
    Pietzner, Klaus
    Charite, Germany .
    Wimberger, Pauline
    Technical University of Dresden, Germany .
    Vergote, Ignace
    University Hospital Leuven, Belgium .
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Schneeweiss, Andreas
    University of Heidelberg Hospital, Germany .
    Bokemeyer, Carsten
    University of Medical Centre Hamburg Eppendorf, Germany .
    Salat, Christoph
    Hematol Oncology Clin, Germany .
    Scambia, Giovanni
    Catholic University, Italy .
    Berton-Rigaud, Dominique
    CLCC Rene Gauducheau, France .
    Santoro, Armando
    Humanitas Cancer Centre, Italy .
    Cervantes, Andres
    University of Valencia, Spain .
    Tredan, Olivier
    Centre Leon Berard, France .
    Tournigand, Christophe
    Hop St Antoine, France .
    Colombo, Nicoletta
    University of Milano Bicocca, Italy .
    Dudnichenko, Alexander S.
    Kharkov Medical Academic Postgrad Educ, Ukraine .
    Westermann, Anneke
    University of Amsterdam, Netherlands .
    Friccius-Quecke, Hilke
    Neovu Biotech GmbH, Germany .
    Lordick, Florian
    University of Cancer Centre Leipzig, Germany .
    Catumaxomab with and without prednisolone premedication for the treatment of malignant ascites due to epithelial cancer: results of the randomised phase IIIb CASIMAS study2014Ingår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, nr 8, s. 76-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This two-arm, randomised, multicentre, open-label, phase IIIb study investigated the safety and efficacy of a 3-h catumaxomab infusion with/without prednisolone premedication to reduce catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a co-primary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (catumaxomab plus prednisolone, 4.1; catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the catumaxomab plus prednisolone arm than in the catumaxomab arm, but the differences were not statistically significant (p = 0.402 and 0.599, respectively). Median OS was longer in the catumaxomab plus prednisolone arm than in the catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant (p = 0.186). The superiority of catumaxomab plus prednisolone versus catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main catumaxomab-related adverse events. The study confirms the safety and efficacy of catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites.

  • 26.
    Sorbe, B.
    et al.
    Department of Gynecological Oncology, University Hospital, Örebro, Sweden, Department of Gynecological Oncology, University Hospital, SE-701 85 Örebro, Sweden.
    Andersson, H.
    Department of Gynecological Oncology, University Hospital, Gothenburg, Sweden.
    Boman, K.
    Department of Gynecological Oncology, University Hospital, Umeå, Sweden.
    Rosenberg, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Kalling, M.
    Department of Gynecologic Oncology, University Hospital, Lund, Sweden.
    Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel - Long-term follow-up2008Ingår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 18, nr 4, s. 803-808Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m2) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer. © 2007, Copyright the Authors.

  • 27.
    Stalberg, Karin
    et al.
    Uppsala Univ, Sweden.
    Bjurberg, Maria
    Skane Univ Hosp Lund, Sweden; Lund Univ, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Carlson, Joseph
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Dahm-Kahler, Pernilla
    Gothenburg Univ, Sweden.
    Floter-Radestad, Angelique
    Karolinska Inst, Sweden.
    Hellman, Kristina
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Holmberg, Erik
    Sahlgrens Acad, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Marcickiewicz, Janusz
    Reg Canc Ctr Vast, Sweden; Hallands Hosp Varberg, Sweden.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Tholander, Bengt
    Uppsala Univ, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer - a Swedish Gynecologic Cancer Group (SweGCG) studyIngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226XArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69-8.07, p amp;lt; .001) followed by deep myometrial invasion (RR = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.

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  • 28.
    Stålberg, Karin
    et al.
    Uppsala University, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Bjurberg, M.
    Skånes University of Sjukhus, Sweden; Lund University, Sweden.
    Borgfeldt, C.
    Lund University, Sweden.
    Dahm-Kahler, P.
    University of Gothenburg, Sweden.
    Falconer, H.
    Karolinska Institute, Sweden.
    Holmberg, E.
    Sahlgrens University Hospital, Sweden; Gothenburg University, Sweden.
    Staf, C.
    Sahlgrens University Hospital, Sweden.
    Tholander, B.
    Uppsala University Hospital, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Karolinska Institute, Sweden.
    Rosenberg, Per
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper.
    Högberg, T.
    Lund University, Sweden.
    Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register studyOn behalf of the Swedish Gynecological Cancer Group2017Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, nr 12, s. 2693-2700Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI50% (risk ratio [RR]=4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not. Whats new? Whether lymphadenectomy is beneficial for women with endometrial cancer remains uncertain. Moreover, additional studies are needed to explore factors that reliably predict lymph node metastasis (LNM). Here, multiple factors, including tumor histology, grade of differentiation and DNA aneuploidy, were evaluated for associations with LNM risk in women with endometrial cancer and verified lymph node status. Most significantly, deep myometrial invasion in tumors increased LNM risk fourfold, whereas DNA ploidy had essentially no impact on LNM risk. The findings confirm the predictive relevance of myometrial invasion, histology and grade reported in previous single-center and multicenter studies.

  • 29.
    von Heideman, Anne
    et al.
    Uppsala University, Sweden .
    Tholander, Bengt
    Uppsala University, Sweden .
    Grundmark, Birgitta
    Uppsala University, Sweden .
    Cajander, Stefan
    Karolinska Institute, Sweden .
    Gerdin, Eva
    Uppsala University, Sweden .
    Holm, Leif
    Falun Central Hospital, Sweden .
    Axelsson, Agneta
    Vasteras Hospital, Sweden .
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Mahteme, Haile
    Uppsala University, Sweden .
    Daniel, Erika
    Uppsala University, Sweden .
    Larsson, Rolf
    Uppsala University, Sweden .
    Nygren, Peter
    Uppsala University, Sweden .
    Chemotherapeutic drug sensitivity of primary cultures of epithelial ovarian cancer cells from patients in relation to tumour characteristics and therapeutic outcome2014Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 2, s. 242-250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. A number of chemotherapeutic drugs are active in epithelial ovarian cancer (EOC) but so far choice of drugs for treatment is mostly empirically based. Testing of drug activity in tumour cells from patients might provide a rationale for a more individualised approach for drug selection. Material and methods. Sensitivity of EOC to chemotherapeutic drugs was analysed in 125 tumour samples from 112 patients using a short-term primary culture assay based on the concept of total cell kill. Sensitivity was related to tumour histology, treatment status and clinical tumour response. Results. For most EOC standard drugs serous high grade and clear cell EOC were the most sensitive subtypes and the mucinous tumours the most resistant subtype. Docetaxel, however, tended to show the opposite pattern. Samples from previously treated patients tended to be more resistant than those from treatment naive patients. The activity of cisplatin correlated with that of other drugs with the exception of docetaxel. Tumour samples from two sites in the same patient at the same occasion showed similar cisplatin sensitivity in contrast to samples taken at different occasions. Samples from patients responding in the clinic to treatment were more sensitive to most drugs than samples from non-responding patients. At the individual patient level, drug sensitivity in vitro compared with clinical response showed sensitivities and specificities in the 83-100% and 55-83% ranges, respectively. Conclusions. Assessment of EOC tumour cell drug sensitivity in vitro provides clinically relevant and potentially useful information for the optimisation of drug treatment.

  • 30.
    Wedin, Madelene
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten, Forum Östergötland.
    Ahlner, Eva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Falk, Annika
    Norrlands Univ Hosp, Sweden.
    Sandstrom, Asa
    Norrlands Univ Hosp, Sweden.
    Lindahl, Gabriel
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rosenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Validation of the Lymphoedema Quality of Life Questionnaire (LYMQOL) in Swedish cancer patients2020Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 59, nr 3, s. 365-371Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this study was to validate a translated Swedish version of the lymphoedema-specific quality of life questionnaire (LYMQOL) in a cohort of Swedish cancer patients with secondary lymphoedema of the limbs after cancer treatment.

    Material and methods: We recruited 102 patients with lymphoedema of the arms or legs after cancer treatment who were visiting lymphoedema therapists at the departments of oncology at the university hospitals in Linköping and Umeå. The LYMQOL questionnaires were translated forward and backward from English to Swedish. Content and face validity were evaluated. The construct validity was assessed by comparing the LYMQOL with the Short Form Health Survey (SF-36) and the perceived degree of lymphoedema of the limbs, respectively. Reliability was determined through test-retest. The internal consistency was assessed by determining Cronbach’s alpha and by factor analysis.

    Results: The content and face validity assessments showed that LYMQOL was an easy, clear and not too long questionnaire to use for patients with lymphoedema. Construct validity was high in both versions when compared with the SF-36. The association between the degrees of perceived lymphoedema and the LYMQOL was only significant in the domains Function and Body Image in the arm version, whereas all domains in the leg version were significant. The reliability was good for the arm version (intra-class-correlation coefficients 0.53–0.87) and very good for the leg version (intra-class-correlation coefficients 0.78–0.90). The internal consistency was acceptable to excellent, with Cronbach’s alpha values between 0.79–0.93 (arm-version) and 0.87–0.94 (leg-version). The factor analysis confirmed the usefulness of the four domains in the LYMQOL versions.

    Conclusions: This study confirmed the validity of the Swedish version of LYMQOL and demonstrated that LYMQOL may be a simple and useful tool for use in clinical practice and scientific contexts for evaluating QoL in patients with lymphoedema of the limbs.

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