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  • 1.
    Armuand, Gabriela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Skoog-Svanberg, Agneta
    Uppsala University, Uppsala, Sweden.
    Correction: Reproductive Patterns Among Childhood and Adolescent Cancer Survivors in Sweden: A Population-Based Matched-Cohort Study (vol 35, pg 1577, 2018)2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 20Article in journal (Other academic)
    Abstract [en]

    n/a

  • 2.
    Armuand, Gabriela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Skoog-Svanberg, Agneta
    Uppsala University, Uppsala, Sweden.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Reproductive Patterns Among Childhood and Adolescent Cancer Survivors in Sweden: A Population-Based Matched-Cohort Study.2017In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 35, no 14, p. 1577-1583Article in journal (Refereed)
    Abstract [en]

    Purpose To compare the probability of a first live birth, age at time of birth, and time between diagnosis/referent date and birth between childhood and adolescent cancer survivors and an age-matched comparison group. Materials and Methods A total of 1,206 survivors was included in the study, together with 2,412 age-matched individuals from the general population. A Cox proportional hazards model was used to investigate first live birth after diagnosis/referent date. Data were stratified by sex, age at diagnosis, and diagnostic era (ie, diagnosis before 1988 v in 1988 or later). Results Overall, the probability of having a first live birth (hazard ratio [HR]) was significantly lower; men had lower HRs than women (HR, 0.65 v 0.79). There were no significant differences in the probability of having a first live birth among women diagnosed during adolescence (HR, 0.89), but the HR was lower among women with childhood cancers (HR, 0.47). Among male survivors, the situation was the opposite; men diagnosed during adolescence had lower HRs than survivors of childhood cancer (HR, 0.56 v 0.70). Examination of the data from the two diagnostic eras (before 1988 and 1988 or later) shows that the HR increased among female survivors after 1988 (HR, 0.71 v 0.90) and decreased among male survivors (HR, 0.72 v 0.59). A shorter time had elapsed between diagnosis/referent date and the birth of a first child among both male and female survivors compared with controls. In addition, female survivors were younger at time of birth. Conclusion The study demonstrates reduced probability of having a first live birth among cancer survivors diagnosed during childhood or adolescence; men were particularly vulnerable.

  • 3.
    Barlesi, Fabrice
    et al.
    Hop Marseille, AP HP, Marseille, France.
    Scherpereel, Arnaud
    Univ Lille, Ctr Hosp Reg, Hop A Calmette, Lille, France.
    Rittmeyer, Achim
    Lungenfachklin Immenhausen, Immenhausen, Germany.
    Pazzola, Antonio
    Osped Civile Santissima, Sassari, Italy.
    Ferrer Tur, Neus
    Hosp Son Llatzer, Palma De Mallorca, Spain.
    Kim, Joo-Hang
    Yonsei Univ, Coll Med, Seoul 120749, South Korea.
    Ahn, Myung-Ju
    Sungkyunkwan Univ, Sch Med, Seoul, South Korea.
    Aerts, Joachim G J V
    Amphia Hosp, Breda, Netherlands.
    Gorbunova, Vera
    NN Blokhin Canc Res Ctr Russia, Moscow, Russia.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Wong, Elaine K
    F Hoffmann Roche, Basel, Switzerland.
    Perez-Moreno, Pablo
    F Hoffmann Roche, Basel, Switzerland.
    Mitchell, Lada
    F Hoffmann Roche, Basel, Switzerland.
    Groen, Harry J M
    Univ Med Ctr Groningen, Groningen, Netherlands.
    Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089).2013In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, no 24, p. 3004-3011Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Maintenance therapy is associated with improved survival in patients with non-small-cell lung cancer (NSCLC), but few studies have compared active agents in this setting. AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment.

    PATIENTS AND METHODS: Patients with advanced nonsquamous NSCLC received first-line bevacizumab 7.5 mg/kg, cisplatin 75 mg/m(2), and pemetrexed 500 mg/m(2) once every 3 weeks for four cycles. Those achieving response or stable disease were randomly assigned at a ratio of 1:1 to maintenance bevacizumab 7.5 mg/kg or bevacizumab 7.5 mg/kg plus pemetrexed 500 mg/m(2) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) after random assignment.

    RESULTS: In total, 376 patients received induction treatment, 71.9% achieved disease control, and 67.3% were randomly assigned to maintenance therapy, with 125 and 128 receiving single-agent bevacizumab and bevacizumab plus pemetrexed treatment, respectively. At a median follow-up of 8.1 months, PFS from random assignment was significantly improved in the bevacizumab plus pemetrexed arm (median, 3.7 v 7.4 months; hazard ratio, 0.48; 95% CI, 0.35 to 0.66; P < .001) per a stratified model. The PFS benefit extended across age, performance status, smoking history, and induction response (stable disease v partial response) subgroups. Any grade, grade ≥ 3, and serious adverse events occurred more often with bevacizumab plus pemetrexed maintenance. No new safety signals were observed.

    CONCLUSION: In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.

  • 4.
    Bjorkholm, M.
    et al.
    Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden, Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Derolf, A.R.
    Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
    Hultcrantz, M.
    Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden, Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Kristinsson, S.Y.
    Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekstrand, C.
    Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
    Goldin, L.R.
    National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
    Andreasson, B.
    Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Birgegard, G.
    Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Linder, O.
    Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Malm, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology UHL.
    Markevarn, B.
    Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Nilsson, L.
    Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Samuelsson, J.
    Swedish Chronic Myeloproliferative Neoplasm Study Group, Stockholm, Sweden.
    Granath, F.
    Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
    Landgren, O.
    Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
    Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 17, p. 2410-2415Article in journal (Refereed)
    Abstract [en]

    Purpose: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU). Methods: On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk. Results: Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P32), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P32 greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation. Conclusion: The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P32 and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors. © 2011 by American Society of Clinical Oncology.

  • 5. du Bois, Andreas
    et al.
    Herrstedt, Jørn
    Hardy-Bessard, Anne-Claire
    Müller, Hans-Helge
    Harter, Philipp
    Kristensen, Gunnar
    Joly, Florence
    Huober, Jens
    Åvall-Lundqvist, Elisabeth
    Karolinska University Hospital, Stockholm, Sweden.
    Weber, Béatrice
    Kurzeder, Christian
    Jelic, Svetislav
    Pujade-Lauraine, Eric
    Burges, Alexander
    Pfisterer, Jacobus
    Gropp, Martina
    Staehle, Anne
    Wimberger, Pauline
    Jackisch, Christian
    Sehouli, Jalid
    Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer.2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 27, p. 4162-4169Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 6.
    Ekholm, Maria
    et al.
    Lund University, Sweden; Ryhov County Hospital, Sweden.
    Bendahl, Par-Ola
    Lund University, Sweden.
    Ferno, Marten
    Lund University, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Ryden, Lisa
    Lund University, Sweden.
    Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 19, p. 2232-+Article in journal (Refereed)
    Abstract [en]

    Purpose The aim of this study was to evaluate the long-term effect of 2 years of adjuvant tamoxifen compared with no systemic treatment (control) in premenopausal patients with breast cancer over different time periods through long-term (amp;gt; 25 years) follow-up. Patients and Methods Premenopausal patients with primary breast cancer (N = 564) were randomly assigned to 2 years of tamoxifen (n = 276) or no systemic treatment (n = 288). Data regarding date and cause of death were obtained from the Swedish Cause of Death Register. End points were cumulative mortality (CM) and cumulative breast cancer-related mortality (CBCM). The median follow-up for the 250 patients still alive in April 2014 was 26.3 years (range, 22.7 to 29.7 years). Results In patients with estrogen receptor-positive tumors (n = 362), tamoxifen was associated with a marginal reduction in CM (hazard ratio [HR], 0.77; 95% CI, 0.58 to 1.03; P = .075) and a significant reduction in CBCM (HR, 0.73; 95% CI, 0.53 to 0.99; P = .046). The effect seemed to vary over time (CM years 0 to 5: HR, 1.05; 95% CI, 0.64 to 1.73; years amp;gt;5 to 15: HR, 0.58; 95% CI, 0.37 to 0.91; and after 15 years: HR, 0.82; 95% CI, 0.48 to 1.42; CBCM years 0 to 5: HR, 1.09; 95% CI, 0.65 to 1.82; years amp;gt;5 to 15: HR, 0.53; 95% CI, 0.33 to 0.86; and after 15 years: HR, 0.72; 95% CI, 0.36 to 1.44). Conclusion Two years of adjuvant tamoxifen resulted in a long-term survival benefit in premenopausal patients with estrogen receptor-positive primary breast cancer. (C) 2016 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

  • 7.
    Eriksson, Hanna
    et al.
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Månsson-Brahme, Eva
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Frohm-Nilsson, Margareta
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Ingvar, Christian
    Lund University, Sweden.
    Lindholm, Christer
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Naredi, Peter
    Sahlgrenska Academy, Gothenburg, Sweden.
    Stierner, Ulrika
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health and Society. Linköping University, Faculty of Arts and Sciences.
    Hansson, Johan
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone: a nationwide population-based study from Sweden2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 13, p. 1356-1364Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM).

    METHODS:

    This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based registers followed up through 2012.

    RESULTS:

    After adjustment for age at diagnosis, level of education, living area, period of diagnosis, and tumor site, the odds ratios (ORs) of higher stage at diagnosis were significantly increased among men living alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI, 1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR for stage II versus stage I disease was also increased among women living alone (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed earlier, the CMM-specific survival was significantly decreased among men living alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P < .001). After additional adjustments for all potential and established prognostic factors, CMM-specific survival among men living alone versus men living with a partner remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P < .001), suggesting a residual adverse effect on survival not accounted for by these parameters.

    CONCLUSION:

    In all age groups among men, living alone is significantly associated with reduced CMM-specific survival, partially attributed to a more advanced stage at diagnosis. This emphasizes the need for improved prevention and early detection strategies for this group.

  • 8. Gore, Martin
    et al.
    Huinink, Wim ten Bakkel
    Carmichael, James
    Gordon, Alan
    Davidson, Neville
    Coleman, Robert
    Spaczynski, Marek
    Héron, Jean-Francois
    Bolis, Giorgio
    Malmström, Henric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Malfetano, John
    Scarabelli, Claudio
    Vennin, Phillipe
    Ross, Graham
    Fields, Scott
    Clinical evidence for topotecan-paclitaxel non-cross-resistance in ovarian cancer.2001In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 19, p. 1893-1900Article in journal (Refereed)
  • 9. Gorin, Norbert-Claude
    et al.
    Labopin, Myriam
    Boiron, Jean-Michel
    Theorin, Niklas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Littlewood, Tim
    Slavin, Shimon
    Greinix, Hildegard
    Cahn, Jean Yves
    Alessandrino, E. Paolo
    Rambaldi, Alessandro
    Nagler, Arnon
    Polge, Emmanuelle
    Rocha, Vanderson
    Results of genoidentical hemopoietic stem cell transplantation with reduced intensity conditioning for acute myelocytic leukemia: Higher doses of stem cells infused benefit patients receiving transplants in second remission or beyond - The acute leukemia 2006In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 24, no 24, p. 3959-3966Article in journal (Refereed)
    Abstract [en]

    Purpose Nucleated cell dose is an important and modifiable factor in hematopoietic stem cell transplantation (HSCT), however its association with outcomes in the context of reduced intensity conditioning regimen (RIC) HSCT for adults with acute myelocytic leukemia (AML) is not known. Patients and Methods From 1998 to 2003, 253 patients with de novo AML, received transplants with RIC and peripheral blood from a genoidentical donor. Median age was 55 years (range, 18 to 72) and the median follow-up was 17 months (range, 2 to 67). One hundred forty one patients received transplants in first remission (CRI), 47 received transplants in second remission (CR2), and 65 patients received transplants in a more advanced phase. Fludarabin-based RIC was used in, 91%, of patients and low-dose (<4 Gy) total-body radiation in 23% of patients. The median nucleated and CD34 cell dose infused were 9.1 x 10(8)/kg and 5.8 x 10(6)/kg, respectively. Results,. Overall, 2-year leukemia-free survival (LFS) was 41% +/- 4% and it was 46% +/- 5% for patients receiving a higher cell dose (>9.1 x 10(8)/kg) and 37% +/- 5% for the remainders (P = .03). Higher cell doses exclusively benefited patients who received transplantations in CR2 or beyond, with LFS of 47 +/- 8 versus 20 +/- 8, with no detectable effect for patients who received transplants in CR1. In a multivariate analysis of the overall patient population, higher nucleated cell dose cells were associated with higher LFS (P = .04), higher incidence of chronic graft-versus-host disease (P = .01), and there was a trend towards a lower relapse incidence (P = .06). Interestingly, CD34+ cell dose was not associated with any outcomes. Conclusion Nucleated cell dose is an important factor that can be modified to improve results of RIC for patients with AML transplanted later than om CR1.

  • 10. Hansson, Johan
    et al.
    Bergenmar, Mia
    Hofer, Per-Ake
    Lundell, Goeran
    Mansson-Brahme, Eva
    Ringborg, Ulrik
    Synnerstad, Ingrid
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bratel, Annika Ternesten
    Wennberg, Ann-Marie
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Monitoring of kindreds with hereditary predisposition for cutaneous melanoma and dysplastic nevus syndrome: Results of a Swedish preventive program2007In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 25, no 19, p. 2819-2824Article in journal (Refereed)
    Abstract [en]

    Purpose To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. Patients and Methods Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. Results Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. Conclusion This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.

  • 11. Hermes, Andreas
    et al.
    Bergman, Bengt
    Bremnes, Roy
    Ek, Lars
    Fluge, Sverre
    Sederholm, Christer
    Sundstrøm, Stein
    Thaning, Lars
    Vilsvik, Jan
    Aasebø, Ulf
    Sörenson, Sverre
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pulmonary Medicine . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine UHL.
    Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial2008In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, no 26, p. 4261-4267Article in journal (Refereed)
  • 12.
    Holmberg, Lars
    et al.
    Kings Coll London, Div Canc Studies, London SE1 9RT, England.
    Garmo, Hans
    Regional Oncologic Center, University Hospital, Uppsala.
    Granstrand, Bengt
    Norrland University Hospital, Umeå.
    Ringberg, Anita
    Malmö University Hospital.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sandelin, Kerstin
    Karolinska Hospital, Stockholm.
    Karlsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Anderson, Harald
    University Hospital, Lund.
    Emdin, Stefan
    Norrland University Hospital, Umeå.
    Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast2008In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, no 8, p. 1247-1252Article in journal (Refereed)
    Abstract [en]

    Purpose Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast (DCIS) in patient groups as defined by age, size of the lesion, focality, completeness of excision and mode of detection. Patients and Methods A total of 1,067 women in Sweden were randomly assigned to either postoperative radiotherapy (RT) or control from 1987 to 1999, and 1,046 were followed for a mean of 8 years. The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat. Results There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years (95% CI, 10.3% to 21.6%) and a relative risk of 0.40 (95% CI, 0.30 to 0.54). There was no statistically significant difference in distant metastasis free survival. There was an effect modification by age, yielding a low effect of RT in women younger than 50, but substantial protection in women older than 60 years. The age effect was not confounded by focality, lesion size, completeness of excision, or detection mode. There was no group as defined by our stratification variables that had a low risk without radiotherapy. Conclusion Our results indicate that younger women have a low protective effect of conventional RT after sector resection. Older women benefit substantially. We caution that the age effect was seen in a subgroup analysis. Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful.

  • 13.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Bax expression decreases significantly from primary tumor to metastasis in colorectal cancer2002In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 20, no 3, p. 811-816Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Bax is a proapoptotic member of the bcl-2 family. Previous studies about Bax have shown that the expression increases from normal to tumor tissue, but the clinical significance is contradictory. Our aims were to analyze the expression of Bax from normal mucosa to primary tumor and to metastases in colorectal cancer patient. We further investigated whether low Bax expression in the primary tumor or changed expression from normal mucosa to primary tumor and to metastases had biologic and clinical significance.

    PATIENTS AND METHODS: The study included 135 patients with primary colorectal adenocarcinoma, of whom 31 had metastases in the lymph nodes and 75 had normal mucosa. Immunohistochemistry, DNA sequencing, and microsatellite analysis were used to detect Bax expression, mutations, and microsatellite instability.

    RESULTS: The protein was observed in 132 of 135 tumors, all normal epithelial cells and metastases. The frequencies of weak expression were greater from well/moderately to poorly differentiated and to mucinous carcinomas. Bax expression was stronger from normal to tumor tissue, but subsequently decreased in metastases. The matched cases with lower expression in the metastases than in the primary tumor showed a more infiltrative growth pattern and more distal metastases.

    CONCLUSION: The association of Bax expression with tumor differentiation/histologic types and a decreased expression in the metastases, suggests that Bax expression may be involved in tumor differentiation/histologic types and metastatic progression. We also propose the novel notion that changed Bax expression in the metastases compared with the primary tumors might provide information to determine the clinicopathologic characteristics of the tumor.

  • 14. Lens, MB
    et al.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Ahlbom, A
    Farahmand, BY
    Synnerstad, Ingrid
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Boeryd, B
    Bishop, JAN
    Effect of pregnancy on survival in women with cutaneous malignant melanoma2004In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 22, no 21, p. 4369-4375Article in journal (Refereed)
    Abstract [en]

    Purpose An adverse influence of pregnancy on the risk of death in women with cutaneous melanoma was suggested historically by anecdotal reports. Previous studies included small numbers of women observed for short periods. Methods Using data from the Swedish National and Regional Registries, we performed a retrospective cohort study of all Swedish women who were diagnosed with cutaneous melanoma during their reproductive period, from January 1, 1958, to December 31, 1999. The relationship between pregnancy status at the diagnosis of melanoma and overall survival was examined in multivariable proportional-hazards models. Results The cohort comprised 185 women (3.3%) diagnosed with melanoma during pregnancy and 5,348 (96.7%) women of the same childbearing age diagnosed with melanoma while not pregnant. There was no statistically significant difference in overall survival between pregnant and nonpregnant groups (log-rank chi(2)1 [r] = 0.84, P =.361). Pregnancy status at the time of diagnosis of melanoma was not related to survival in a multivariable Cox model in the 2,101 women (hazard ratio for death in the pregnant group was 1.08, 95% Cl, 0.60 to 1.93). In the multivariable analysis, pregnancy status after diagnosis of melanoma was not a significant predictor of survival (hazard ratio for death in women who had pregnancy subsequent to the diagnosis of melanoma was 0.58, 95% Cl, 0.32 to 1.05). Conclusion The survival of pregnant women with melanoma is not worse than the survival of nonpregnant women with melanoma. Pregnancy subsequent to the diagnosis of primary melanoma was not associated with an increased risk of death. (C) 2004 by American Society of Clinical Oncology.

  • 15.
    Pujade-Lauraine, Eric
    et al.
    Hôpital Hôtel-Dieu, Paris, France .
    Wagner, Uwe
    Philipps University Marburg, Marburg, Germany.
    Åvall-Lundqvist, Elisabeth
    Karolinska University Hospital, Stockholm, Sweden.
    Gebski, Val
    NHMRC Clinical Trials Centre, Sydney, NSW, Australia.
    Heywood, Mark
    BC Cancer Agency, Vancouver, BC, Canada .
    Vasey, Paul A
    Wesley Medical Centre, Auchenflower, QLD, Australia .
    Volgger, Birgit
    Medical University Innsbruck, Innsbruck, Austria .
    Vergote, Ignace
    University Hospital Leuven, Leuven, Belgium.
    Pignata, Sandro
    Cancer National Institute, Naples, Italy .
    Ferrero, Annamaria
    Gynecological Oncology Institute for Cancer Research and Treatment (IRCC) of Candiolo & AO Ordine Mauriziano, Turin, Italy .
    Sehouli, Jalid
    University Hospital Charité, Berlin, Germany .
    Lortholary, Alain
    Centre Catherine De Sienne, Nantes, France.
    Kristensen, Gunnar
    Norwegian Radium Hospital, Oslo, Norway .
    Jackisch, Christian
    Klinikum Offenbach, Offenbach, Germany .
    Joly, Florence
    CHU-Centre François Baclesse, Caen, France.
    Brown, Chris
    NHMRC Clinical Trials Centre, Sydney, NSW, Australia .
    Le Fur, Nathalie
    ARCAGY-GINECO, Paris, France .
    du Bois, Andreas
    Dr Horst Schmidt Klinik, Wiesbaden, Germany .
    Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse.2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 20, p. 3323-3329Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 16.
    Richter, Johan
    et al.
    Skåne University Hospital, Sweden.
    Soderlund, Stina
    University Hospital, Uppsala, Sweden.
    Lubking, Anna
    Skåne University Hospital, Sweden.
    Dreimane, Arta
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Markevarm, Berit
    University Hospital, Umeå, Sweden.
    Sjalander, Anders
    Umeå University, Sweden.
    Saussele, Susanne
    Univ Med Mannheim, Mannheim, Germany.
    Olsson-Stromberg, Ulla
    University Hospital, Uppsala, Sweden.
    Stenke, Leif
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Letter: Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Discontinuation of Imatinib: A Tyrosine Kinase Inhibitor Withdrawal Syndrome? in JOURNAL OF CLINICAL ONCOLOGY, vol 32, issue 25, pp 2821-28232014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 25, p. 2821-2823Article in journal (Other academic)
    Abstract [en]

    n/a

  • 17.
    Russo, Antonio
    et al.
    Università di Palermo.
    Bazan, Viviana
    Università di Palermo.
    Iacopetta, Barry
    University of Western Australia.
    Kerr, David
    University of Oxford.
    Soussi, Thierry
    Hôpital Tenon, Paris.
    Gebbia, Nicola
    Università di Palermo.
    The TP53 colorectal cancer international collaborative study on the prognostic and predictive significance of p53 mutation: influence of tumor site, type of mutation, and adjuvant treatment.2005In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 23, no 30, p. 7518-7528Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aims of the TP53 Colorectal Cancer (CRC) International Collaborative Study were to evaluate the possible associations between specific TP53 mutations and tumor site, and to evaluate the prognostic and predictive significance of these mutations in different site, stage, and treatment subgroups. PATIENTS AND METHODS: A total of 3,583 CRC patients from 25 different research groups in 17 countries were recruited to the study. Patients were divided into three groups according to site of the primary tumor. TP53 mutational analyses spanned exons 4 to 8. RESULTS: TP53 mutations were found in 34% of the proximal colon tumors and in 45% of the distal colon and rectal tumors. They were associated with lymphatic invasion in proximal tumors. In distal colon tumors, deletions causing loss of amino acids were associated with worse survival. In proximal colon tumors, mutations in exon 5 showed a trend toward statistical significance (P < .05) when overall survival was considered. Dukes' C tumors with wild-type TP53 and those with mutated TP53 (proximal tumors) showed significantly better prognosis when treated with adjuvant chemotherapy. CONCLUSION: Analysis of TP53 mutations from a large cohort of CRC patients has identified tumor site, type of mutation, and adjuvant treatment as important factors in determining the prognostic significance of this genetic alteration.

  • 18. Ryden, L
    et al.
    Jirstrom, K
    Bendahl, PA
    Ferno, M
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Thorstenson, Sten
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Jonsson, PE
    Landberg, G
    Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor receptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer2005In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 23, no 21, p. 4695-4704Article in journal (Refereed)
    Abstract [en]

    Purpose Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance.

    Patients and Methods Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors.

    Results VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER–positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor–positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status.

    Conclusion Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor–positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.

  • 19.
    Schleiermacher, Gudrun
    et al.
    Institute National Sante and Rech Medical U830, France; Institute Curie, France.
    Javanmardi, Niloufar
    University of Gothenburg, Sweden.
    Bernard, Virginie
    Institute Curie, France.
    Leroy, Quentin
    Institute Curie, France.
    Cappo, Julie
    Institute National Sante and Rech Medical U830, France.
    Rio Frio, Thomas
    Institute Curie, France.
    Pierron, Gaelle
    Institute Curie, France.
    Lapouble, Eve
    Institute Curie, France.
    Combaret, Valerie
    Centre Leon Berard, France.
    Speleman, Frank
    Ghent University Hospital, Belgium.
    de Wilde, Bram
    Ghent University Hospital, Belgium.
    Djos, Anna
    University of Gothenburg, Sweden.
    Ora, Ingrid
    Lund University, Sweden.
    Hedborg, Fredrik
    Uppsala University, Sweden; Uppsala University, Sweden.
    Traeger, Catarina
    Astrid Lindgren Childrens Hospital, Sweden.
    Holmqvist, Britt-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Abrahamsson, Jonas
    University of Gothenburg, Sweden.
    Peuchmaur, Michel
    Hop University of Robert Debre, France; University of Paris 07, France.
    Michon, Jean
    Institute Curie, France.
    Janoueix-Lerosey, Isabelle
    Institute National Sante and Rech Medical U830, France.
    Kogner, Per
    Astrid Lindgren Childrens Hospital, Sweden.
    Delattre, Olivier
    Institute National Sante and Rech Medical U830, France.
    Martinsson, Tommy
    University of Gothenburg, Sweden.
    Emergence of New ALK Mutations at Relapse of Neuroblastoma2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 25, p. 2727-+Article in journal (Refereed)
    Abstract [en]

    Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. Methods We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000 x deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. Results All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). Conclusion In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.

  • 20.
    Sederholm, Christer
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pulmonary Medicine . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine UHL.
    Hillerdal, G.
    Hillerdal, G..
    Lamberg, K.
    Lamberg, K..
    Kolbeck, K.
    Kölbeck, K..
    Dufmats, M.
    Dufmats, M..
    Westberg, R.
    Westberg, R..
    Gawande, S.R.
    Gawande, S.R..
    Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: The Swedish Lung Cancer Study Group2005In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 23, no 33, p. 8380-8388Article in journal (Refereed)
    Abstract [en]

    Purpose: This phase III study compared overall survival in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when treated with single-agent gemcitabine versus gemcitabine/carboplatin. Secondary objectives were to compare response, time to progression, toxicity, and quality of life. Patients and Methods: Chemotherapy-naive patients received either gemcitabine alone (1,250 mg/m2 on days 1 and 8, gemcitabine arm) or with carboplatin (area under the curve 5 on day 1, GC arm) every 21 days. Results: Demographics and disease characteristics of 334 randomly assigned patients were comparable on both arms. An intent-to-treat analysis showed significantly better overall survival (log-rank P = .0205) and 2-year survival (15% v 5%, P = .009) favoring the GC arm. Per Cox multivariate analysis, only two covariates, treatment arm (GC v G) and baseline performance status (0 or 1 v 2), independently influenced survival. Per-protocol analyses showed significantly longer median time to progression (5.7 v 3.9 months, P = .0001) and significantly higher objective response rate (29.6 v 11.3%, P < .0001) in the GC arm. Grade 3 to 4 leucopenia and thrombocytopenia were significantly more pronounced in the GC arm (P for both variables < .001) but importantly without associated increases in fever, infection, bleeding, or hospitalizations. There was no discernible difference in global quality-of-life patterns between treatment arms. Conclusion: In advanced NSCLC, gemcitabine/carboplatin therapy resulted in significant survival benefit compared with single-agent gemcitabine without undue increase in toxicity. © 2005 by American Society of Clinical Oncology.

  • 21.
    Sun, Xiao-Feng
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Rütten, Sabine
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Expression of the deleted in colorectal cancer gene is related to prognosis in DNA diploid and low proliferative colorectal adenocarcinoma.1999In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 17, p. 1745-1750Article in journal (Refereed)
  • 22. Tidefelt, U
    et al.
    Liliemark, J
    Gruber, A
    Sundman-Engberg, B
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Stenke, L
    Elmhorn-Rosenborg, A
    Möllgård, L
    Lehman, S
    Xu, D
    Covelli, A
    Gustavsson, B
    Paul, C
    Liliemark, E
    P-glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of Deunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia.2000In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 18, p. 1837-1844Article in journal (Refereed)
  • 23.
    Tveit, Kjell Magne
    et al.
    Oslo University Hospital, Norway.
    Guren, Tormod
    Uppsala Hospital, Sweden Karolinska Institute, Sweden .
    Pfeiffer, Per
    Odense University Hospital, Denmark .
    Sorbye, Halfdan
    Haukeland Hospital, Norway University of Bergen, Norway .
    Pyrhonen, Seppo
    Turku University Hospital, Finland .
    Sigurdsson, Fridbjorn
    National University Hospital Reykjavik, Iceland .
    Kure, Elin
    University of Oslo, Norway .
    Fokstuen, Tone
    Karolinska Institute, Sweden .
    Hansen, Flemming
    Aarhus University Hospital, Denmark .
    Hofsli, Eva
    St Olavs Hospital, Norway .
    Birkemeyer, Elke
    Stavanger University Hospital, Norway .
    Johnsson, Anders
    University of Lund Hospital, Sweden .
    Starkhammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Karen Yilmaz, Mette
    Aalborg University Hospital, Denmark .
    Keldsen, Nina
    Herning Regional Hospital, Denmark .
    Berit Erdal, Anne
    Haukeland Hospital, Norway University of Bergen, Norway .
    Christoffersen, Thoralf
    University of Oslo, Norway .
    Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-VII Study2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 15, p. 1755-1762Article in journal (Refereed)
    Abstract [en]

    Purpose less thanbrgreater than less thanbrgreater thanThe NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. less thanbrgreater than less thanbrgreater thanPatients and Methods less thanbrgreater than less thanbrgreater thanPatients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanOf the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. less thanbrgreater than less thanbrgreater thanConclusion less thanbrgreater than less thanbrgreater thanCetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.

  • 24.
    Warnberg, Fredrik
    et al.
    Uppsala University, Sweden.
    Garmo, Hans
    Uppsala University, Sweden; Kings Coll London, England.
    Emdin, Stefan
    Umeå University Hospital, Sweden.
    Hedberg, Veronica
    Gavle Central Hospital, Sweden.
    Adwall, Linda
    Uppsala University, Sweden.
    Sandelin, Kerstin
    Karolinska University Hospital, Sweden.
    Ringberg, Anita
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Karlsson, Per
    Sahlgrens University Hospital, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Anderson, Harald
    Lund University, Sweden.
    Jirstrom, Karin
    Lund University, Sweden.
    Holmberg, Lars
    Uppsala University, Sweden; Kings Coll London, England.
    Effect of Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma in Situ: 20 Years Follow-Up in the Randomized SweDCIS Trial2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 32, p. 3613-+Article in journal (Refereed)
    Abstract [en]

    Purpose Four randomized studies show that adjuvant radiotherapy (RT) lowers the risk of subsequent ipsilateral breast events (IBEs) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) by approximately 50% after 10 to 15 years. We present 20 years of follow-up data for the SweDCIS trial. Patients and Methods Between 1987 and 1999 1,046 women were randomly assigned to RT or not after BCS for primary DCIS. Results up to 2005 have been published, and we now add another 7 years of follow-up. All breast cancer events and causes of death were registered. Results There were 129 in situ and 129 invasive IBEs. Absolute risk reduction in the RT arm was 12.0% at 20 years (95% CI, 6.5 to 17.7), with a relative risk reduction of 37.5%. Absolute reduction was 10.0% (95% CI, 6.0 to 14.0) for in situ and 2.0% (95% CI, -3.0 to 7.0) for invasive IBEs. There was a nonstatistically significantly increased number of contralateral events in the RT arm (67 v 48 events; hazard ratio, 1.38; 95% CI, 0.95 to 2.00). Breast cancer-specific death and overall survival were not influenced. Younger women experienced a relatively higher risk of invasive IBE and lower effect of RT. The hazard over time looked different for in situ and invasive IBEs. Conclusion Use of adjuvant RT is supported by 20-year follow-up. Modest protection against invasive recurrences and a possible increase in contralateral cancers still call for a need to find groups of patients for whom RT could be avoided or mastectomy with breast reconstruction is indicated.

  • 25.
    Zardavas, Dimitrios
    et al.
    Breast Int Grp, Belgium.
    te Marvelde, Luc
    Canc Council, Australia.
    Milne, Roger L.
    Canc Council, Australia; Univ Melbourne, Australia.
    Fumagalli, Debora
    Breast Int Grp, Belgium.
    Fountzilas, George
    Aristotle Univ Thessaloniki, Greece.
    Kotoula, Vassiliki
    Aristotle Univ Thessaloniki, Greece.
    Razis, Evangelia
    Hygeia Hosp, Greece.
    Papaxoinis, George
    Hippokrateion Hosp, Greece.
    Joensuu, Heikki
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Moynahan, Mary Ellen
    Mem Sloan Kettering Canc Ctr, NY 10021 USA.
    Hennessy, Bryan T.
    Beaumont Hosp, Ireland; Royal Coll Surg, Ireland.
    Bieche, Ivan
    Curie Inst, France.
    Saal, Lao H.
    Lund Univ, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Iacopetta, Barry
    Univ Western Australia, Australia.
    Jensen, Jeanette Dupont
    Univ Southern Denmark, Denmark.
    OToole, Sandra
    Garvan Inst Med Res, Australia.
    Lopez-Knowles, Elena
    Garvan Inst Med Res, Australia; Royal Marsden NHS Trust, England; Inst Canc Res, England.
    Barbaraeschi, Mattia
    Santa Chiara Hosp, Italy.
    Noguchi, Shinzaburo
    Osaka Univ, Japan.
    Azim, Hatem A. Jr.
    Amer Univ Beirut, Lebanon.
    Lerma, Enrique
    Univ Autonoma Barcelona, Spain.
    Bachelot, Thomas
    Ctr Rech Cancerol Lyon, France.
    Wang, Qing
    Not Found:Linkoping Univ, Linkoping, Sweden.
    Perez Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    de Velde, Cornelis J. H. Can
    Leiden Univ, Netherlands.
    Rea, Daniel W.
    Univ Birmingham, England.
    Sabine, Vicky
    Univ Guelph, Canada.
    Bartlett, John M. S.
    Ontario Inst Canc Res, Canada.
    Sotiriou, Christos
    Univ Libre Bruxelles, Belgium.
    Michiels, Stefan
    Gustave Roussy, France; Univ Paris Saclay, France.
    Loi, Sherene
    Univ Melbourne, Australia.
    Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 10, p. 981-+Article in journal (Refereed)
    Abstract [en]

    PurposePhosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data.Patients and MethodsAssociations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes.ResultsData from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P amp;lt; .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P amp;lt; .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P amp;lt; .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); amp;gt; 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS (P = .043), but not for the DDFS and OS end points.ConclusionIn this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors. (C) 2018 by American Society of Clinical Oncology

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