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  • 1. Aapro, Matti
    et al.
    Beguin, Yves
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gascon, Pere
    Hedenus, Michael
    Österborg, Anders
    Too-Low Iron Doses and Too Many Dropouts in Negative Iron Trial?2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 17, p. E525-E526Article in journal (Refereed)
  • 2.
    Abrahamsson, Jonas
    et al.
    Queen Silvia Children’s Hospital, Gothenburg.
    Forestier, Erik
    Heldrup, Jesper
    Jahnukainen, Kirsi
    Jónsson, Olafur G.
    Lausen, Birgitte
    Palle, Josefine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Zeller, Bernward
    Hasle, Henrik
    Aarhus University Hospital Skejby, Aarhus.
    Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 3, p. 310-315Article in journal (Refereed)
    Abstract [en]

    Purpose

    To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.

    Patients and Methods

    All Nordic children with AML younger than 15 years (n = 151) were treated on the Nordic Society for Pediatric Hematology and Oncology (NOPHO) AML 2004 protocol. After the first course of idarubicin, cytarabine, etoposide, and 6-thioguanin, patients with good response were allowed hematologic recovery before the second course, whereas patients with a poor (>= 15% blasts) or intermediate (5% to 14.9% blasts) were recommended to proceed immediately with therapy. Patients not in remission after the second course received fludarabine, cytarabine, and granulocyte colony-stimulating factor. Poor responders received allogeneic stem-cell transplantation (SCT) as consolidation.

    Results

    Seventy-four percent of patients had good response, 17% had intermediate response, and 7% had poor response after the first course. The overall remission frequency was 97.4%, with 92% in remission after the second course. The rate of induction death was 1.3%. Patients with an intermediate response had a lower event-free survival of 35% compared with good (61%) and poor responders (82%).

    Conclusion

    The NOPHO-AML 2004 induction strategy gives an excellent remission rate with low toxic mortality in an unselected population. Outcome is worse in patients with intermediate response but may be improved by intensifying consolidation in this group using SCT.

  • 3. Andersen, Niels S.
    et al.
    Pedersen, Lone B.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Elonen, Erkki
    Kolstad, Arne
    Boesen, Anne Marie
    Pedersen, Lars M.
    Lauritzsen, Grete F.
    Ekanger, Roald
    Nilsson-Ehle, Herman
    Nordstrom, Marie
    Freden, Susanne
    Jerkeman, Mats
    Eriksson, Mikael
    Vaart, Jaan
    Malmer, Beatrice
    Geisler, Christian H.
    Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma2009In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, no 26, p. 4365-4370Article in journal (Refereed)
    Abstract [en]

    Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.

  • 4.
    Andersson, Yvette
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Frisell, Jan
    Sylvan, Maria
    de Boniface, Jana
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Breast Cancer Survival in Relation to the Metastatic Tumor Burden in Axillary Lymph Nodes2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 17, p. 2868-2873Article in journal (Refereed)
    Abstract [en]

    Purpose The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer. Patients and Methods Between September 2000 and January 2004, 3,369 patients with breast cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival. Results Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ. Conclusion This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.

  • 5.
    Angenendt, Linus
    et al.
    Univ Hosp Munster, Munster, Germany.
    Röllig, Christoph
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Montesinos, Pau
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Martinez-Cuadron, David
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Barragan, Eva
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Garcia, Raimundo
    Gen Hosp Castellon, Castellon de La Plana, Spain.
    Botella, Carmen
    Hosp Gen Alicante, Alicante, Spain.
    Martinez, Pilar
    Hosp 12 Octubre, Madrid, Spain.
    Ravandi, Farhad
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kadia, Tapan
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kantarjian, Hagop M.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Cortes, Jorge
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.
    Lazarevic, Vladimir
    Lund Univ, Lund, Sweden.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lehmann, Sören
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Recher, Christian
    CHU Toulouse, Toulouse, France.
    Pigneux, Arnaud
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Bertoli, Sarah
    CHU Toulouse, Toulouse, France.
    Dumas, Pierre-Yves
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Dombret, Herve
    Paris Diderot Univ, Paris, France.
    Preudhomme, Claude
    Inst Natl Sante & Rech Med Lille, Lille, France.
    Micol, Jean-Baptiste
    Paris Saclay Univ, Gustave Roussy, Villejuif, France.
    Terre, Christine
    Ctr Transfus Sanguine, Le Chesnay, France.
    Racil, Zdenek
    Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic.
    Novak, Jan
    Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Prague, Czech Republic.
    Zak, Pavel
    Charles Univ Prague, Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic.
    Wei, Andrew H.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Tiong, Ing S.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Wall, Meaghan
    St Vincents Hosp, Melbourne, Vic, Australia.
    Estey, Elihu
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Shaw, Carole
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Exeler, Rita
    Univ Munster, Munster, Germany.
    Wagenführ, Lisa
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stölzel, Friedrich
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Thiede, Christian
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stelljes, Matthias
    Univ Hosp Munster, Munster, Germany.
    Lenz, Georg
    Univ Hosp Munster, Munster, Germany.
    Mikesch, Jan-Henrik
    Univ Hosp Munster, Munster, Germany.
    Serve, Hubert
    Univ Hosp Frankfurt, Frankfurt, Germany.
    Ehninger, Gerhard
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Berdel, Wolfgang E.
    Univ Hosp Munster, Munster, Germany.
    Kramer, Michael
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Krug, Utz
    Klinikum Leverkusen, Leverkusen, Germany.
    Schliemann, Christoph
    Univ Hosp Munster, Munster, Germany.
    Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts2019In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, no 29, p. 2632-2642Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.

    METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.

    RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.

    CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.

  • 6. Armuand, Gabriela M.
    et al.
    Rodriguez-Wallberg, Kenny A.
    Wettergren, Lena
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lampic, Claudia
    Sex Differences in Fertility-Related Information Received by Young Adult Cancer Survivors2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 17, p. 2147-2153Article in journal (Refereed)
    Abstract [en]

    Purpose The aim was to investigate male and female cancer survivors' perception of fertility-related information and use of fertility preservation (FP) in connection with cancer treatment during reproductive age.

    Methods The study sample consisted of cancer survivors diagnosed from 2003 to 2007 identified in population-based registers in Sweden. Inclusion criteria included survivors who were age 18 to 45 years at diagnosis and had lymphoma, acute leukemia, testicular cancer, ovarian cancer, or female breast cancer treated with chemotherapy. Of 810 eligible participants, 484 survivors (60% response rate) completed a postal questionnaire.

    Results The majority of male participants reported having received information about treatment impact on fertility (80%) and FP (68%), and more than half of the men banked frozen sperm (54%). Among women, less than half (48%) reported that they received information about treatment impact on fertility, and 14% reported that they received information about FP. Only seven women (2%) underwent FP. Predictors for receiving information about treatment impact on fertility were a pretreatment desire to have children (odds ratio [OR], 3.5), male sex (OR, 3.2), and being <= 35 years of age at diagnosis (OR, 2.0). Predictors for receiving information about FP included male sex (OR, 14.4), age <= 35 at diagnosis (OR, 5.1), and having no children at diagnosis (OR, 2.5).

    Conclusion Our results show marked sex differences regarding the receipt of fertility-related information and use of FP. There is an urgent need to develop fertility-related information adapted to female patients with cancer to improve their opportunities to participate in informed decisions regarding their treatment and future reproductive ability.

  • 7. Armuand, Gabriela
    et al.
    Skoog-Svanberg, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bladh, Marie
    Sydsjö, Gunilla
    Reproductive Patterns Among Childhood and Adolescent Cancer Survivors in Sweden: A Population-Based Matched-Cohort Study2017In: 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.

  • 8. Avall-Lundqvist, Elisabeth
    et al.
    Staf, Christian
    Bjurberg, Maria
    Borgfeldt, Christer
    Dahm-Kahler, Pernilla
    Falconer, Henrik
    Holmberg, Erik
    Kjolhede, Preben
    Stålberg, Karin Glimskär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Rosenberg, Per
    Hogberg, Thomas
    A population-based study of pelvic serous carcinoma in Sweden: Primary site, FIGO stage and survival.2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15Article in journal (Other academic)
  • 9. Baccarani, Michele
    et al.
    Cortes, Jorge
    Pane, Fabrizio
    Niederwieser, Dietger
    Saglio, Giuseppe
    Apperley, Jane
    Cervantes, Francisco
    Deininger, Michael
    Gratwohl, Alois
    Guilhot, François
    Hochhaus, Andreas
    Horowitz, Mary
    Hughes, Timothy
    Kantarjian, Hagop
    Larson, Richard
    Radich, Jerald
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Silver, Richard T.
    Goldman, John
    Hehlmann, Rudiger
    Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet2009In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, no 35, p. 6041-6051Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE: To review and update the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia with imatinib and second-generation tyrosine kinase inhibitors (TKIs), including monitoring, response definition, and first- and second-line therapy. METHODS: These recommendations are based on a critical and comprehensive review of the relevant papers up to February 2009 and the results of four consensus conferences held by the panel of experts appointed by ELN in 2008. RESULTS: Cytogenetic monitoring was required at 3, 6, 12, and 18 months. Molecular monitoring was required every 3 months. On the basis of the degree and the timing of hematologic, cytogenetic, and molecular results, the response to first-line imatinib was defined as optimal, suboptimal, or failure, and the response to second-generation TKIs was defined as suboptimal or failure. CONCLUSION: Initial treatment was confirmed as imatinib 400 mg daily. Imatinib should be continued indefinitely in optimal responders. Suboptimal responders may continue on imatinb, at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.

  • 10. Barbui, Tiziano
    et al.
    Barosi, Giovanni
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cervantes, Francisco
    Finazzi, Guido
    Griesshammer, Martin
    Harrison, Claire
    Hasselbalch, Hans Carl
    Hehlmann, Rudiger
    Hoffman, Ronald
    Kiladjian, Jean-Jacques
    Kroeger, Nicolaus
    Mesa, Ruben
    McMullin, Mary F.
    Pardanani, Animesh
    Passamonti, Francesco
    Vannucchi, Alessandro M.
    Reiter, Andreas
    Silver, Richard T.
    Verstovsek, Srdan
    Tefferi, Ayalew
    Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 6, p. 761-770Article in journal (Refereed)
    Abstract [en]

    We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first-and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

  • 11. Baumann, Pia
    et al.
    Nyman, Jan
    Hoyer, Morten
    Wennberg, Berit
    Gagliardi, Giovanna
    Lax, Ingmar
    Drugge, Ninni
    Ekberg, Lars
    Friesland, Signe
    Johansson, Karl-Axel
    Lund, Jo-Asmund
    Morhed, Elisabeth
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Levin, Nina
    Paludan, Merete
    Sederholm, Christer
    Traberg, Anders
    Wittgren, Lena
    Lewensohn, Rolf
    Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.2009In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, no 20, p. 3290-6Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study.

    PATIENTS AND METHODS: Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume.

    RESULTS: Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027).

    CONCLUSION: With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.

  • 12. Bernhard, Jürg
    et al.
    Dietrich, Daniel
    Scheithauer, Werner
    Gerber, Daniela
    Bodoky, György
    Ruhstaller, Thomas
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bajetta, Emilio
    Schüller, Johannes
    Saletti, Piercarlo
    Bauer, Jean
    Figer, Arie
    Pestalozzi, Bernhard C.
    Köhne, Claus-Henning
    Mingrone, Walter
    Stemmer, Salomon M.
    Tàmas, Karin
    Kornek, Gabriela V.
    Koeberle, Dieter
    Herrmann, Richard
    Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.0012008In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, no 22, p. 3695-3701Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.

  • 13. Berruti, Alfredo
    et al.
    Fassnacht, Martin
    Baudin, Eric
    Hammer, Gary
    Haak, Harm
    Leboulleux, Sophie
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Allolio, Bruno
    Terzolo, Massimo
    Adjuvant therapy in patients with adrenocortical carcinoma: a position of an international panel2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 23, p. e401-e402Article in journal (Refereed)
  • 14.
    Biccler, Jorne Lionel
    et al.
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Solna, Sweden.
    Eloranta, Sandra
    Karolinska Inst, Solna, Sweden.
    Smeland, Knut B.
    Oslo Univ Hosp, Oslo, Norway.
    Brown, Peter de Nully
    Copenhagen Univ Hosp, Copenhagen, Denmark.
    Jakobsen, Lasse Hjort
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    Frederiksen, Henrik
    Odense Univ Hosp, Odense, Denmark.
    Jerkeman, Mats
    Lund Univ, Lund, Sweden.
    Fosså, Alexander
    Oslo Univ Hosp, Oslo, Norway;KG Jebsen Ctr B Cell Malignancies, Oslo, Norway.
    Andersson, Therese M. L.
    Karolinska Inst, Solna, Sweden.
    Holte, Harald
    Oslo Univ Hosp, Oslo, Norway;KG Jebsen Ctr B Cell Malignancies, Oslo, Norway.
    Bögsted, Martin
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    El-Galaly, Tarec Christoffer
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    Smedby, Karin E.
    Karolinska Inst, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Relapse Risk and Loss of Lifetime After Modern Combined Modality Treatment of Young Patients With Hodgkin Lymphoma: A Nordic Lymphoma Epidemiology Group Study2019In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, no 9, p. 703-713Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Estimates of short- and long-term survival for young patients with classic Hodgkin lymphoma (cHL) are of considerable interest. We investigated cHL prognosis in the era of contemporary treatment at different milestones during the follow-up.

    PATIENTS AND METHODS: On the basis of a Nordic cohort of 2,582 patients diagnosed at ages 18 to 49 years between 2000 and 2013, 5-year relapse risks and 5-year restricted losses in expectation of lifetime were estimated for all patients and for patients who achieved event-free survival (EFS) for 12 (EFS12), 24 (EFS24), 36 (EFS36) or 60 (EFS60) months. The median follow-up time was 9 years (range, 2.9 to 16.8 years).

    RESULTS: The 5-year overall survival was 95% (95% CI, 94% to 96%). The 5-year risk of relapse was 13.4% (95% CI, 12.1% to 14.8%) overall but decreased to 4.2% (95% CI, 3.8% to 4.6%) given that patients reached EFS24. Relapse risk for patients treated with six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) was comparable to that of patients treated with six to eight courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) despite more adverse risk criteria among patients treated with BEACOPP. Both from diagnosis and if EFS24 was reached, the losses in expectation of lifetime during the following 5 years were small (from diagnosis, 45 days [95% CI, 35 to 54 days] and for patients who reached EFS24, 13 days [95% CI, 7 to 20 days]). In stage-stratified analyses of 5-year restricted loss in expectation of lifetime, patients with stages I to IIA disease had no noteworthy excess risk of death after they reached EFS24, whereas risk remained measurable for patients with stages IIB to IV cHL.

    CONCLUSION: Real-world data on young patients with cHL from the Nordic countries show excellent outcomes. The outlook is particularly favorable for patients who reach EFS24, which supports limited relapse-oriented clinical follow-up.

  • 15. Björkholm, Magnus
    et al.
    Derolf, Asa R
    Hultcrantz, Malin
    Kristinsson, Sigurdur Y
    Ekstrand, Charlotta
    Goldin, Lynn R
    Andreasson, Björn
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Linder, Olle
    Malm, Claes
    Markevärn, Berit
    Nilsson, Lars
    Samuelsson, Jan
    Granath, Fredrik
    Landgren, Ola
    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 (P(32)), 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 P(32) 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 P(32) 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.

  • 16. Björkholm, Magnus
    et al.
    Ohm, Lotta
    Eloranta, Sandra
    Derolf, Åsa
    Hultcrantz, Malin
    Sjöberg, Jan
    Andersson, Therese
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Richter, Johan
    Landgren, Ola
    Kristinsson, Sigurdur Y.
    Dickman, Paul W.
    Success Story of Targeted Therapy in Chronic Myeloid Leukemia: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 20082011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 18, p. 2514-2520Article in journal (Refereed)
    Abstract [en]

    Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% CIs) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.

  • 17. Bower, Hannah
    et al.
    Björkholm, Magnus
    Dickman, Paul W
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lambert, Paul C
    Andersson, Therese M-L
    Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 24, p. 2851-2858Article in journal (Refereed)
    Abstract [en]

    PURPOSE: A dramatic improvement in the survival of patients with chronic myeloid leukemia (CML) occurred after the introduction of imatinib mesylate, the first tyrosine kinase inhibitor (TKI). We assessed how these changes affected the life expectancy of patients with CML and life-years lost as a result of CML between 1973 and 2013 in Sweden.

    MATERIALS AND METHODS: Patients recorded as having CML in the Swedish Cancer Registry from 1973 to 2013 were included in the study and followed until death, censorship, or end of follow-up. The life expectancy and loss in expectation of life were predicted from a flexible parametric relative survival model.

    RESULTS: A total of 2,662 patients with CML were diagnosed between 1973 and 2013. Vast improvements in the life expectancy of these patients were seen over the study period; larger improvements were seen in the youngest ages. The great improvements in life expectancy translated into great reductions in the loss in expectation of life. Patients of all ages diagnosed in 2013 will, on average, lose < 3 life-years as a result of CML.

    CONCLUSION: Imatinib mesylate and new TKIs along with allogeneic stem cell transplantation and other factors have contributed to the life expectancy in patients with CML approaching that of the general population today. This will be an important message to convey to patients to understand the impact of a CML diagnosis on their life. In addition, the increasing prevalence of patients with CML will have a great effect on future health care costs as long as continuous TKI treatment is required.

  • 18.
    Bower, Hannah
    et al.
    Karolinska Institutet.
    Björkholm, Magnus
    Karolinska Univ Hosp.
    Dickman, Paul W
    Karolinska Institutet.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lambert, Paul C
    Karolinska institutet; University of Leicester.
    Andersson, Therese M-L
    Karolinska institutet.
    Reply to D. Pulte et al.2017In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 35, no 6, p. 696-697Article in journal (Refereed)
  • 19. Braendengen, Morten
    et al.
    Tveit, Kjell M.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Birkemeyer, Elke
    Frykholm, Gunilla
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wiig, Johan N.
    Byström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Bujko, Krzysztof
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer2008In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, no 22, p. 3687-3694Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate. PATIENTS AND METHODS: The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109). RESULTS: The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity. CONCLUSION: CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.

  • 20. Brunner, Nils
    et al.
    Tarpgaard, Line Schmidt
    Christensen, Ib Jarle
    Moreira, Jose
    Guren, Tormod Kyrre
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sorby, Halfdan
    Ikdahl, Tone
    Kure, Elin
    Tveit, Kjell Magne
    Nielsen, Hans Jorgen
    Pfeiffer, Per
    Benefit of EGFR-inhibition therapy for metastatic colorectal cancer patients with KRAS-mutated tumors and high plasma TIMP-I level: Results from the NORDIC VII study2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 15Article in journal (Refereed)
  • 21. Bushnell, David L.
    et al.
    O'Dorisio, Thomas M.
    O'Dorisio, M. Sue
    Menda, Yusuf
    Hicks, Rodney J.
    Van Cutsem, Eric
    Baulieu, Jean-Louis
    Borson-Chazot, Francoise
    Anthony, Lowell
    Benson, Al B.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Grossman, Ashley B.
    Connolly, Mary
    Bouterfa, Hakim
    Li, Yong
    Kacena, Katherine A.
    LaFrance, Norman
    Pauwels, Stanislas A.
    90Y-edotreotide for metastatic carcinoid refractory to octreotide2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 10, p. 1652-1659Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Metastatic carcinoid is an incurable malignancy whose symptoms, such as diarrhea and flushing, can be debilitating and occasionally life-threatening. Although symptom relief is available with octreotide, the disease eventually becomes refractory to octreotide, leaving no proven treatment options. The goal of this study was to evaluate the clinical effect of using (90)Y-edotreotide to treat symptomatic patients with carcinoid tumors. PATIENTS AND METHODS: Patients enrolled had metastatic carcinoid, at least one sign/symptom refractory to octreotide, and at least one measurable lesion. Study treatment consisted of three cycles of 4.4 GBq (120 mCi) (90)Y-edotreotide each, once every 6 weeks. RESULTS: Ninety patients were enrolled in the study. Using Southwest Oncology Group tumor response criteria, 67 (74.%) of 90 patients (95% CI, 65.4% to 83.4%) were objectively stable or responded. A statistically significant linear trend toward improvement was demonstrated across all 12 symptoms assessed. Median progression-free survival was significantly greater (P = .03) for the 38 patients who had durable diarrhea improvement than the 18 patients who did not (18.2 v 7.9 months, respectively). Adverse events (AEs) were reported in 96.7% (87 of 90) of patients. These AEs consisted primarily of reversible GI events (76 of 90), which could be caused in part by concomitant administration of amino acid solution given to reduce radiation exposure to the kidneys. There was one case each of grade 3 oliguria and grade 4 renal failure, each lasting 6 days. CONCLUSION: (90)Y-edotreotide treatment improved symptoms associated with malignant carcinoid among subjects with no treatment alternatives. Treatment was well-tolerated and had an acceptable expected AE profile.

  • 22.
    Carde, Patrice
    et al.
    Gustave Roussy Canc Campus, F-94805 Villejuif, France..
    Karrasch, Matthias
    European Org Res & Treatment, Canc Headquarters, Brussels, Belgium..
    Fortpied, Catherine
    European Org Res & Treatment, Canc Headquarters, Brussels, Belgium..
    Brice, Pauline
    Hop St Louis, Paris, France..
    Khaled, Hussein
    Natl Canc Inst, Cairo, Egypt..
    Casasnovas, Olivier
    Ctr Hosp Univ CHU Dijon, Dijon, France..
    Caillot, Denis
    Ctr Hosp Univ CHU Dijon, Dijon, France..
    Gaillard, Isabelle
    CHU Henri Mondor, F-94010 Creteil, France..
    Bologna, Serge
    Ctr Hosp Reg Univ CHR Nancy, Nancy, France..
    Ferme, Christophe
    Gustave Roussy Canc Campus, F-94805 Villejuif, France..
    Lugtenburg, Pieternella Johanna
    Erasmus MC, Inst Canc, Rotterdam, Netherlands..
    Morschhauser, Frank
    CHR Lille, Lille, France..
    Aurer, Igor
    Univ Hosp Ctr Zagreb, Zagreb, Croatia..
    Coiffier, Bertrand
    CHU Lyon, Lyon, France..
    Meyer, Ralph
    Juravinski Canc Ctr, Hamilton, ON, Canada..
    Seftel, Matthew
    Canc Care Manitoba, Winnipeg, MB, Canada..
    Wolf, Max
    Peter MacCallum Canc Inst, East Melbourne, Vic, Australia..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sureda, Anna
    Hosp Santa Creu & Sant Pau, Barcelona, Spain..
    Mounier, Nicolas
    Hop Archet, Nice, France..
    Eight Cycles of ABVD Versus Four Cycles of BEACOPP(escalated) Plus Four Cycles of BEACOPP(baseline) in Stage III to IV, International Prognostic Score >= 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 17, p. 2028-+Article in journal (Refereed)
    Abstract [en]

    Purpose To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Patients and Methods Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD(8)) or escalated-dose BEACOPP (BEACOPP(escalated)) for four cycles followed by baseline BEACOPP (BEACOPP(baseline)) for four cycles (BEACOPP(4+4)) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients. Results Between 2002 and 2010, 549 patients were randomly assigned to ABVD(8) (n = 275) or BEACOPP(4+4) (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; "B" symptoms, 81%; and International Prognostic Score >= 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-upwas 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD(8) versus 69.3% for BEACOPP(4+4) (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD(8) and BEACOPP(4+4) arms, respectively. Conclusion ABVD(8) and BEACOPP(4+4) resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP(4+4) did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD(8), treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.

  • 23.
    Carde, Patrice P.
    et al.
    Gustave Roussy Canc Campus, Villejuif, France..
    Grynberg, Michael
    Hop Jean Verdier, Bondy, France..
    Poirot, Catherine
    Hop St Louis, Paris, France..
    Glimelius, Bengt
    Univ Uppsala Hosp, Uppsala, Sweden..
    Mounier, Nicolas
    LArchet Hosp, Nice, France..
    How Relevant Is Treatment-Related Infertility for Individual Treatment Selection in Hodgkin Lymphoma?: Reply2017In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 35, no 3, p. 374-+Article in journal (Refereed)
  • 24.
    Chen, Robert
    et al.
    City Hope Natl Med Ctr, Natl Med Ctr, Duarte, CA USA.
    Zinzani, Pier Luigi
    Univ Bologna, Bologna, Italy.
    Fanale, Michelle A.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Armand, Philippe
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Johnson, Nathalie A.
    Jewish Gen Hosp, Montreal, PQ, Canada.
    Brice, Pauline
    Hop St Louis, Paris, France.
    Radford, John
    Christie NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England;Univ Manchester, Manchester, Lancs, England.
    Ribrag, Vincent
    Inst Gustave Roussy, Villejuif, France.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Vassilakopoulos, Theodoros P.
    Univ Athens, Laikon Gen Hosp, Athens, Greece.
    Tomita, Akihiro
    Nagoya Univ, Grad Sch Med, Nagoya, Aichi, Japan.
    von Tresckow, Bastian
    Univ Hosp Cologne, Cologne, Germany.
    Shipp, Margaret A.
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Zhang, Yinghua
    Merck, Kenilworth, NJ USA.
    Ricart, Alejandro D.
    Merck, Kenilworth, NJ USA.
    Balakumaran, Arun
    Merck, Kenilworth, NJ USA.
    Moskowitz, Craig H.
    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
    Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma2017In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 35, no 19, p. 2125-2132Article in journal (Refereed)
    Abstract [en]

    Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response >= 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

  • 25. d'Amore, Francesco
    et al.
    Relander, Thomas
    Lauritzsen, Grete F.
    Jantunen, Esa
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Anderson, Harald
    Holte, Harald
    Osterborg, Anders
    Merup, Mats
    Brown, Peter
    Kuittinen, Outi
    Erlanson, Martin
    Ostenstad, Bjorn
    Fagerli, Unn-Merete
    Gadeberg, Ole V.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Delabie, Jan
    Ralfkiaer, Elisabeth
    Vornanen, Martine
    Toldbod, Helle E.
    Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-012012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 25, p. 3093-3099Article in journal (Refereed)
    Abstract [en]

    Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study. Patients and Methods Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT. Results Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL. Conclusion Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL. J Clin Oncol 30: 3093-3099. (C) 2012 by American Society of Clinical Oncology

  • 26. Dewdney, Alice
    et al.
    Cunningham, David
    Tabernero, Josep
    Capdevila, Jaume
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cervantes, Andres
    Tait, Diana
    Brown, Gina
    Wotherspoon, Andrew
    de Castro, David Gonzalez
    Chua, Yu Jo
    Wong, Rachel
    Barbachano, Yolanda
    Oates, Jacqueline
    Chau, Ian
    Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 14, p. 1620-1627Article in journal (Refereed)
    Abstract [en]

    Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer.

    Patients and Methods Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX + C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis.

    Results One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX + C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [ HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX + C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX + C arm.

    Conclusion Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

  • 27.
    D'Souza, Anita
    et al.
    Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Dispenzieri, Angela
    Mayo Clin, Rochester, MN USA..
    Wirk, Baldeep
    Seattle Canc Care Alliance, Seattle, WA USA..
    Zhang, Mei-Jie
    Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.;Med Coll Wisconsin, Inst Hlth & Soc, Milwaukee, WI 53226 USA..
    Huang, Jiaxing
    Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Gertz, Morie A.
    Mayo Clin, Rochester, MN USA..
    Kyle, Robert A.
    Mayo Clin, Rochester, MN USA..
    Kumar, Shaji
    Mayo Clin, Rochester, MN USA..
    Comenzo, Raymond L.
    Tufts Med Ctr, Boston, MA USA..
    Gale, Robert Peter
    Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, London, England..
    Lazarus, Hillard M.
    Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA..
    Savani, Bipin N.
    Vanderbilt Univ, Med Ctr, Nashville, TN USA..
    Cornell, Robert F.
    Vanderbilt Univ, Med Ctr, Nashville, TN USA..
    Weiss, Brendan M.
    Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA..
    Vogl, Dan T.
    Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA..
    Freytes, Cesar O.
    South Texas Vet Hlth Care Syst, San Antonio, TX USA.;Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA..
    Scott, Emma C.
    Oregon Hlth & Sci Univ, Knight Canc Inst, Ctr Hematol Malignancies, Portland, OR 97201 USA..
    Landau, Heather J.
    Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA..
    Moreb, Jan S.
    Shands HealthCare, Gainesville, FL USA.;Univ Florida, Gainesville, FL USA..
    Costa, Luciano J.
    Univ Alabama Birmingham, Birmingham, AL USA..
    Ramanathan, Muthalagu
    Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA..
    Callander, Natalie S.
    Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA..
    Kamble, Rammurti T.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Olsson, Richard F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Stockholm, Sweden..
    Ganguly, Siddhartha
    Univ Kansas, Med Ctr, Kansas City, KS 66103 USA..
    Nishihori, Taiga
    Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA..
    Kindwall-Keller, Tamila L.
    Univ Virginia Hlth Syst, Charlottesville, VA USA..
    Wood, William A.
    Univ N Carolina, Chapel Hill, NC USA..
    Mark, Tomer M.
    Weill Cornell Med Coll, New York, NY USA..
    Hari, Parameswaran
    Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 32, p. 3741-+Article in journal (Refereed)
    Abstract [en]

    Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.

  • 28. Dueland, Svein
    et al.
    Kyrre, Tormod
    Hagness, Guren Morten
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Line, Pal-Dag
    Pfeiffer, Per
    Foss, Aksel
    Tveit, Kjell Magne
    Outcome after liver transplantation compared with chemotherapy in colorectal cancer patients with nonresectable liver-only disease.2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 3Article in journal (Other academic)
  • 29. Emanuel, Robyn M
    et al.
    Dueck, Amylou C
    Geyer, Holly L
    Kiladjian, Jean-Jacques
    Slot, Stefanie
    Zweegman, Sonja
    Te Boekhorst, Peter A W
    Commandeur, Suzan
    Schouten, Harry C
    Sackmann, Federico
    Kerguelen Fuentes, Ana
    Hernández-Maraver, Dolores
    Pahl, Heike L
    Griesshammer, Martin
    Stegelmann, Frank
    Doehner, Konstanze
    Lehmann, Thomas
    Bonatz, Karin
    Reiter, Andreas
    Boyer, Francoise
    Etienne, Gabriel
    Ianotto, Jean-Christophe
    Ranta, Dana
    Roy, Lydia
    Cahn, Jean-Yves
    Harrison, Claire N
    Radia, Deepti
    Muxi, Pablo
    Maldonado, Norman
    Besses, Carlos
    Cervantes, Francisco
    Johansson, Peter L
    Barbui, Tiziano
    Barosi, Giovanni
    Vannucchi, Alessandro M
    Passamonti, Francesco
    Andreasson, Bjorn
    Ferarri, Maria L
    Rambaldi, Alessandro
    Samuelsson, Jan
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Tefferi, Ayalew
    Mesa, Ruben A
    Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score: Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 33, p. 4098-4103Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy.

    PATIENTS AND METHODS

    The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers.

    RESULTS 

    MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P < .001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis, respectively. The MPN-SAF TSS strongly correlated with overall quality of life (QOL; r = 0.59; P < .001) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) functional scales (all P < .001 and absolute r ≥ 0.50 except social functioning r = 0.48). No significant trends were present when comparing therapy subgroups. The MPN-SAF TSS had excellent internal consistency (Cronbach's α = .83). Factor analysis identified a single underlying construct, indicating that the MPN-SAF TSS is an appropriate, unified scoring method.

    CONCLUSION

    The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptom study to date. This new prospective scoring method may be used to assess MPN symptom burden in both clinical practice and trial settings.

  • 30.
    Fagerlind, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kettis, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, University Administration, Planning Division.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ring, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Barriers against psychosocial communication: Oncologists' perceptions2013In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, no 30Article in journal (Refereed)
  • 31.
    Friberg, Lena E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Henningsson, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Maas, Hugo
    Nguyen, Laurent
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Model of Chemotherapy-Induced Myelosuppression With Parameter Consistency Across Drugs2002In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 20, no 24, p. 4713-4721Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To develop a semimechanistic pharmacokinetic-pharmacodynamic model describing chemotherapy-induced myelosuppression through drug-specific parameters and system-related parameters, which are common to all drugs.

    PATIENTS AND METHODS:

    Patient leukocyte and neutrophil data after administration of docetaxel, paclitaxel, and etoposide were used to develop the model, which was also applied to myelosuppression data from 2'-deoxy-2'-methylidenecytidine (DMDC), irinotecan (CPT-11), and vinflunine administrations. The model consisted of a proliferating compartment that was sensitive to drugs, three transit compartments that represented maturation, and a compartment of circulating blood cells. Three system-related parameters were estimated: baseline, mean transit time, and a feedback parameter. Drug concentration-time profiles affected the proliferation of sensitive cells by either an inhibitory linear model or an inhibitory E(max) model. To evaluate the model, system-related parameters were fixed to the same values for all drugs, which were based on the results from the estimations, and only drug-specific parameters were estimated. All modeling was performed using NONMEM software.

    RESULTS:

    For all investigated drugs, the model successfully described myelosuppression. Consecutive courses and different schedules of administration were also well characterized. Similar system-related parameter estimates were obtained for the different drugs and also for leukocytes compared with neutrophils. In addition, when system-related parameters were fixed, the model well characterized chemotherapy-induced myelosuppression for the different drugs.

    CONCLUSION:

    This model predicted myelosuppression after administration of one of several different chemotherapeutic drugs. In addition, with fixed system-related parameters to proposed values, and only drug-related parameters estimated, myelosuppression can be predicted. We propose that this model can be a useful tool in the development of anticancer drugs and therapies.

  • 32.
    Friberg, Lena E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Henningsson, Anja
    Maas, Hugo
    Nguyen, Laurent
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Model of chemotherapy-induced myelosuppression with parameter consistency across drugs2002In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 20, no 24, p. 4713-4721Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To develop a semimechanistic pharmacokinetic-pharmacodynamic model describing chemotherapy-induced myelosuppression through drug-specific parameters and system-related parameters, which are common to all drugs.

    PATIENTS AND METHODS:

    Patient leukocyte and neutrophil data after administration of docetaxel, paclitaxel, and etoposide were used to develop the model, which was also applied to myelosuppression data from 2'-deoxy-2'-methylidenecytidine (DMDC), irinotecan (CPT-11), and vinflunine administrations. The model consisted of a proliferating compartment that was sensitive to drugs, three transit compartments that represented maturation, and a compartment of circulating blood cells. Three system-related parameters were estimated: baseline, mean transit time, and a feedback parameter. Drug concentration-time profiles affected the proliferation of sensitive cells by either an inhibitory linear model or an inhibitory E(max) model. To evaluate the model, system-related parameters were fixed to the same values for all drugs, which were based on the results from the estimations, and only drug-specific parameters were estimated. All modeling was performed using NONMEM software.

    RESULTS:

    For all investigated drugs, the model successfully described myelosuppression. Consecutive courses and different schedules of administration were also well characterized. Similar system-related parameter estimates were obtained for the different drugs and also for leukocytes compared with neutrophils. In addition, when system-related parameters were fixed, the model well characterized chemotherapy-induced myelosuppression for the different drugs.

    CONCLUSION:

    This model predicted myelosuppression after administration of one of several different chemotherapeutic drugs. In addition, with fixed system-related parameters to proposed values, and only drug-related parameters estimated, myelosuppression can be predicted. We propose that this model can be a useful tool in the development of anticancer drugs and therapies.

  • 33.
    Fristedt, Richard
    et al.
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Hedner, Charlotta
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Borg, David
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Nodin, Björn
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Eberhard, Jakob
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Jirström, Karin
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Prognostic impact of tumor-associated B-cells and plasma cells in esophageal and gastric adenocarcinoma2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 4Article in journal (Other academic)
  • 34. Geyer, Holly
    et al.
    Scherber, Robyn
    Kosiorek, Heidi
    Dueck, Amylou C
    Kiladjian, Jean-Jacques
    Xiao, Zhijian
    Slot, Stefanie
    Zweegman, Sonja
    Sackmann, Federico
    Fuentes, Ana Kerguelen
    Hernández-Maraver, Dolores
    Döhner, Konstanze
    Harrison, Claire N
    Radia, Deepti
    Muxi, Pablo
    Besses, Carlos
    Cervantes, Francisco
    Johansson, Peter L
    Andreasson, Bjorn
    Rambaldi, Alessandro
    Barbui, Tiziano
    Bonatz, Karin
    Reiter, Andreas
    Boyer, Francoise
    Etienne, Gabriel
    Ianotto, Jean-Christophe
    Ranta, Dana
    Roy, Lydia
    Cahn, Jean-Yves
    Maldonado, Norman
    Barosi, Giovanni
    Ferrari, Maria L
    Gale, Robert Peter
    Birgegard, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Xu, Zefeng
    Zhang, Yue
    Sun, Xiujuan
    Xu, Junqing
    Zhang, Peihong
    Te Boekhorst, Peter A W
    Commandeur, Suzan
    Schouten, Harry
    Pahl, Heike L
    Griesshammer, Martin
    Stegelmann, Frank
    Lehmann, Thomas
    Senyak, Zhenya
    Vannucchi, Alessandro M
    Passamonti, Francesco
    Samuelsson, Jan
    Mesa, Ruben A
    Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 2, p. 151-+Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden.

    PATIENTS AND METHODS: Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly).

    RESULTS: The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S).

    CONCLUSION: The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.

  • 35. Gisselbrecht, Christian
    et al.
    Glass, Bertram
    Mounier, Nicolas
    Gill, Devinder Singh
    Linch, David C.
    Trneny, Marek
    Bosly, Andre
    Ketterer, Nicolas
    Shpilberg, Ofer
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Ma, David
    Briere, Josette
    Moskowitz, Craig H.
    Schmitz, Norbert
    Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era2010In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 28, no 27, p. 4184-4190Article in journal (Refereed)
    Abstract [en]

    Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20(+) DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001). Conclusion In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.

  • 36. Gisselbrecht, Christian
    et al.
    Schmitz, Norbert
    Mounier, Nicolas
    Gill, Devinder Singh
    Linch, David C.
    Trneny, Marek
    Bosly, Andre
    Milpied, Noel J.
    Radford, John
    Ketterer, Nicolas
    Shpilberg, Ofer
    Duehrsen, Ulrich
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ma, David D.
    Viardot, Andreas
    Lowenthal, Ray
    Briere, Josette
    Salles, Gilles
    Moskowitz, Craig H.
    Glass, Bertram
    Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20(+) Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 36, p. 4462-4469Article in journal (Refereed)
    Abstract [en]

    Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20(+) DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P=.7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P<.05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P<.001), as was male sex (P=.01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.

  • 37.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Beets-Tan, Regina
    Blomqvist, Lennart
    Brown, Gina
    Nagtegaal, Iris
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Quirke, Phil
    Valentini, Vincenzo
    van de Velde, Cornelis
    Mesorectal Fascia Instead of Circumferential Resection Margin in Preoperative Staging of Rectal Cancer2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 16, p. 2142-2143Article in journal (Other academic)
  • 38.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hohenberger, Werner Max
    Univ Klinikums Erlangen, Chirurg Klin, Erlangen, Germany..
    Matzel, Klaus E.
    Univ Klinikums Erlangen, Chirurg Klin, Erlangen, Germany..
    Sugihara, Kenichi
    Tokyo Med & Dent Univ, Tokyo, Japan..
    Quirke, Philip
    St James Univ Hosp, Leeds, W Yorkshire, England..
    Further Evaluating the Benefit of Adjuvant Chemotherapy for Colon Cancer Reply2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 30, p. 3713-+Article in journal (Refereed)
  • 39.
    Granberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sissons, Maia
    Kolarova, Teodora
    Goldstein, Grace
    Leyden, John
    Lung neuroendocrine tumor (NET) patient (pt)-reported experience: Results from the first global NET pt surveyA collaboration between the international neuroendocrine cancer alliance (INCA) and Novartis pharmaceuticals.2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15Article in journal (Other academic)
  • 40. Hammel, Pascal
    et al.
    Huguet, Florence
    Van Laethem, Jean-Luc
    Goldstein, David
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Artru, Pascal
    Borbath, Ivan
    Bouche, Olivier
    Shannon, Jenny
    Andre, Thierry
    Mineur, Laurent
    Chibaudel, Benoist
    Bonnetain, Franck
    Louvet, Christophe
    Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study2013In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, no 18, p. LBA4003-Article in journal (Other academic)
  • 41. Henningsson, Anja
    et al.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Viganò, Lucia
    Gianni, Luca
    Verweij, Jaap
    Sparreboom, Alex
    Mechanism-based pharmacokinetic model for paclitaxel2001In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 19, no 20, p. 4065-4073Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    To create a model based on known mechanisms of paclitaxel distribution that could describe the pharmacokinetics (PK) of total and unbound plasma concentrations, as well as blood concentrations. In addition, to investigate the relationship between exposure, based on unbound and total concentrations, and neutropenia.

    PATIENTS AND METHODS

    Paclitaxel and Cremophor EL (CrEL) concentrations were obtained from 23 female and three male patients (50 courses in total) with different cancer types that received paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) (135 to 225 mg/m(2)) as 3- or 24-hour intravenous infusions. Seven of the patients received combination therapy with doxorubicin or cisplatin. The population PK model was built to fit three types of data simultaneously: unbound, total plasma, and blood concentrations. The area under the curve, threshold, and general models were used to relate neutrophil survival fraction from 19 patients (29 courses in total) to exposure based on unbound and total plasma concentration, respectively.

    RESULTS

    The PK model included a linear three-compartment model for unbound concentration, binding directly proportional to CrEL, linear and nonlinear binding to plasma proteins, and linear and nonlinear binding to blood cells. The threshold model best described the PK/pharmacodynamic (PD) relationship for total concentration. No distinction could be made between the models for unbound drug.

    CONCLUSION

    Earlier PK models for paclitaxel have been empirical. This study shows that a mechanistic model can be used to describe the nonlinear PK of paclitaxel. There is an indication that the PK/PD relationship is not the same for unbound and total plasma concentrations.

  • 42. Herrmann, Richard
    et al.
    Bodoky, György
    Ruhstaller, Thomas
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bajetta, Emilio
    Schüller, Johannes
    Saletti, Piercarlo
    Bauer, Jean
    Figer, Arie
    Pestalozzi, Bernhard
    Köhne, Claus-Henning
    Mingrone, Walter
    Stemmer, Salomon M.
    Tàmas, Karin
    Kornek, Gabriela V.
    Koeberle, Dieter
    Cina, Susanne
    Bernhard, Jürg
    Dietrich, Daniel
    Scheithauer, Werner
    Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group2007In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 25, no 16, p. 2212-2217Article in journal (Refereed)
    Abstract [en]

    Purpose: This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer. Patients and Methods: Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Kamofsky performance score (KPS), presence of pain, and disease extent. Results: A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms. Conclusion: GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

  • 43. Hess, Georg
    et al.
    Herbrecht, Raoul
    Romaguera, Jorge
    Verhoef, Gregor
    Crump, Michael
    Gisselbrecht, Christian
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Offner, Fritz
    Strahs, Andrew
    Berkenblit, Anna
    Hanushevsky, Orysia
    Clancy, Jill
    Hewes, Becker
    Moore, Laurence
    Coiffier, Bertrand
    Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma2009In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, no 23, p. 3822-3829Article in journal (Refereed)
    Abstract [en]

    Purpose Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated two dose regimens of temsirolimus in comparison with investigator's choice single-agent therapy in relapsed or refractory disease. Patients and Methods In this multicenter, open-label, phase III study, 162 patients with relapsed or refractory MCL were randomly assigned (1: 1: 1) to receive one of two temsirolimus regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg (175/25-mg) weekly, or investigator's choice therapy from prospectively approved options. The primary end point was progression-free survival (PFS) by independent assessment. Results Median PFS was 4.8, 3.4, and 1.9 months for the temsirolimus 175/75-mg, 175/25-mg, and investigator's choice groups, respectively. Patients treated with temsirolimus 175/75-mg had significantly longer PFS than those treated with investigator's choice therapy (P = .0009; hazard ratio = 0.44); those treated with temsirolimus 175/25-mg showed a trend toward longer PFS (P = .0618; hazard ratio = 0.65). Objective response rate was significantly higher in the 175/75-mg group (22%) compared with the investigator's choice group (2%; P = .0019). Median overall survival for the temsirolimus 175/75-mg group and the investigator's choice group was 12.8 months and 9.7 months, respectively (P = .3519). The most frequent grade 3 or 4 adverse events in the temsirolimus groups were thrombocytopenia, anemia, neutropenia, and asthenia. Conclusion Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate compared with investigator's choice therapy in patients with relapsed or refractory MCL.

  • 44.
    Hjern, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lindblad, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Boman, Krister K.
    Disability in adult survivors of childhood cancer: a Swedish national cohort study2007In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 25, no 33, p. 5262-5266Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We studied the effects of childhood or adolescent cancer and cancer treatment on disability as indicated by persistent aid needs in adult life. PATIENTS AND METHODS: A group of 2,503 survivors of childhood cancer diagnosed before their 16th birthday were studied with data from registers in a national cohort of 1.91 million Swedish residents. Disability indicators were created from information in national registers about income (sickness pension, handicap allowance), personal assistance, and family situation in 2002. Multivariate logistic regression on the log scale was used to estimate relative risk (RR) ratios. RESULTS: A total of 7.6% of survivors received handicap allowance indicating permanent disability, including brain tumors (14.0%), other solid tumors (6.3), and leukemias/lymphomas (2.9%), compared with 0.6% in the general population. Twenty-six percent of survivors of CNS tumor and 10% of survivors of solid tumors had at least one indication of a disability. Younger age at diagnosis suggested a higher risk for disability. CNS tumor survivors had an RR of 10.7 (95% CI, 9.3 to 12.8) for having at least one disability indication compared with the noncancer population, whereas leukemia and lymphoma survivors had an RR of 3.0, and survivors of other cancers had an RR of 3.8. Survivors of CNS tumor only had an increased RR for living in the parental household (RR = 1.6; 95% CI, 1.4 to 1.9). CONCLUSION: Childhood cancer survivors more often have persistent needs of supportive measures provided by community and/or the parental household. The survivors of CNS tumors were at particular risk, indicating a need of safer treatment protocols, and tailored follow-up, prevention, and rehabilitation to address this persistent social disability.

  • 45.
    Hoffman, Lindsey M.
    et al.
    Childrens Hosp Colorado, Aurora, CO USA;Univ Colorado Denver, Aurora, CO USA.
    van Zanten, Sophie E. M. Veldhuijzen
    Vrije Univ, Univ Med Ctr, Amsterdam, Netherlands.
    Colditz, Niclas
    Univ Med Ctr Goettingen, Goettingen, Netherlands.
    Baugh, Joshua
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Chaney, Brooklyn
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Hoffmann, Marion
    Univ Med Ctr Goettingen, Goettingen, Netherlands.
    Lane, Adam
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Fuller, Christine
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Miles, Lili
    Nemours Childrens Hosp, Orlando, FL USA.
    Hawkins, Cynthia
    Hosp Sick Children, Toronto, ON, Canada.
    Bartels, Ute
    Hosp Sick Children, Toronto, ON, Canada.
    Bouffet, Eric
    Hosp Sick Children, Toronto, ON, Canada.
    Goldman, Stewart
    Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
    Leary, Sarah
    Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA;Univ Washington, Seattle Childrens Hosp, Seattle, WA 98195 USA.
    Foreman, Nicholas K.
    Childrens Hosp Colorado, Aurora, CO USA;Univ Colorado Denver, Aurora, CO USA.
    Packer, Roger
    Childrens Natl Hlth Syst, Washington, DC USA.
    Warren, Katherine E.
    NCI, Bethesda, MD 20892 USA.
    Broniscer, Alberto
    St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA.
    Kieran, Mark W.
    Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
    Minturn, Jane
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA;Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
    Comito, Melanie
    Penn State Univ, Hershey, PA USA.
    Broxson, Emmett
    Wright State Univ, Dayton, OH 45435 USA;Childrens Med Ctr, Dayton, OH USA.
    Shih, Chie-Schin
    Indiana Univ, Indianapolis, IN 46204 USA.
    Khatua, Soumen
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Chintagumpala, Murali
    Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA;Baylor Coll Med, Hematol Ctr, Houston, TX 77030 USA.
    Carret, Anne Sophie
    Ctr Hosp Univ St Justine, Montreal, PQ, Canada.
    Escorza, Nancy Yanez
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Hassall, Timothy
    Lady Cilento Childrens Hosp, Brisbane, Qld, Australia.
    Ziegler, David S.
    Sydney Childrens Hosp, Kids Canc Ctr, Randwick, NSW, Australia;Univ New South Wales, Sydney, NSW, Australia.
    Gottardo, Nicholas
    Princess Margaret Hosp Children, Perth, WA, Australia.
    Dholaria, Hetal
    Princess Margaret Hosp Children, Perth, WA, Australia.
    Doughman, Renee
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Benesch, Martin
    Med Univ Graz, Graz, Austria.
    Drissi, Rachid
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Nazarian, Javad
    Childrens Natl Med Ctr, Washington, DC 20010 USA.
    Jabado, Nada
    McGill Univ, Montreal, PQ, Canada.
    Boddaert, Nathalie
    Hop Necker Enfants Malad, Paris, France.
    Varlet, Pascale
    Univ Paris V Descartes, Sorbonne Paris Cite, Hop St Anne, Paris, France.
    Giraud, Geraldine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Univ Paris Saclay, Univ Paris Sud, Gustave Roussy, Villejuif, France.
    Castel, David
    Univ Paris Saclay, Univ Paris Sud, Gustave Roussy, Villejuif, France.
    Puget, Stephanie
    Hop Necker Enfants Malad, Paris, France.
    Jones, Chris
    Inst Canc Res, Sutton, Surrey, England.
    Hulleman, Esther
    Vrije Univ, Univ Med Ctr, Amsterdam, Netherlands.
    Modena, Piergiorgio
    St Anna Como Gen Hosp, Como, Italy.
    Giagnacovo, Marzia
    St Anna Como Gen Hosp, Como, Italy.
    Antonelli, Manila
    Sapienza Univ Rome, Rome, Italy.
    Pietsch, Torsten
    Univ Bonn, Med Ctr, Bonn, Germany.
    Gielen, Gerrit H.
    Univ Bonn, Med Ctr, Bonn, Germany.
    Jones, David T. W.
    German Consortium Translat Canc Res, Heidelberg, Germany;Natl Centrum Tumorerkrankungen Heidelberg, Hopp Childrens Canc Ctr, German Canc Res Ctr, Heidelberg, Germany.
    Sturm, Dominik
    German Consortium Translat Canc Res, Heidelberg, Germany;Natl Centrum Tumorerkrankungen Heidelberg, Hopp Childrens Canc Ctr, German Canc Res Ctr, Heidelberg, Germany;Heidelberg Univ Hosp, Heidelberg, Germany.
    Pfister, Stefan M.
    German Consortium Translat Canc Res, Heidelberg, Germany;Natl Centrum Tumorerkrankungen Heidelberg, Hopp Childrens Canc Ctr, German Canc Res Ctr, Heidelberg, Germany;Heidelberg Univ Hosp, Heidelberg, Germany.
    Gerber, Nicolas U.
    Univ Childrens Hosp Zurich, Zurich, Switzerland.
    Grotzer, Michael A.
    Univ Childrens Hosp Zurich, Zurich, Switzerland.
    Pfaff, Elke
    German Consortium Translat Canc Res, Heidelberg, Germany;Natl Centrum Tumorerkrankungen Heidelberg, Hopp Childrens Canc Ctr, German Canc Res Ctr, Heidelberg, Germany;Heidelberg Univ Hosp, Heidelberg, Germany.
    von Bueren, Andre O.
    Univ Geneva, Geneva, Switzerland;Univ Hosp Geneva, Geneva, Switzerland.
    Hargrave, Darren
    Great Ormond St Hosp Sick Children, London, England.
    Solanki, Guirish A.
    Birmingham Womens & Childrens Hosp, Birmingham, W Midlands, England.
    Cvrlje, Filip Jadrijevic
    Childrens Hosp Zagreb, Zagreb, Croatia.
    Kaspers, Gertjan J. L.
    Vrije Univ, Univ Med Ctr, Amsterdam, Netherlands;Childrens Hosp Zagreb, Zagreb, Croatia.
    Vandertop, William P.
    Acad Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
    Grill, Jacques
    Univ Paris Saclay, Univ Paris Sud, Gustave Roussy, Villejuif, France.
    Bailey, Simon
    Royal Victoria Infirm, Great North Childrens Hosp, Victoria Wing, Newcastle Upon Tyne, Tyne & Wear, England.
    Biassoni, Veronica
    Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, Milan, Italy.
    Massimino, Maura
    Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, Milan, Italy.
    Calmon, Raphael
    Hop Necker Enfants Malad, Paris, France.
    Sanchez, Esther
    Vrije Univ, Univ Med Ctr, Amsterdam, Netherlands.
    Bison, Brigitte
    Univ Med Ctr Goettingen, Goettingen, Netherlands.
    Warmuth-Metz, Monika
    Univ Med Ctr Goettingen, Goettingen, Netherlands.
    Leach, James
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Jones, Blaise
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    van Vuurden, Dannis G.
    Vrije Univ, Univ Med Ctr, Amsterdam, Netherlands.
    Kramm, Christof M.
    Univ Med Ctr Goettingen, Goettingen, Netherlands.
    Fouladi, Maryam
    Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
    Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 19, p. 1963-1972Article in journal (Refereed)
    Abstract [en]

    Purpose

    Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs).

    Materials and Methods

    Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia.

    Results

    Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration (P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002).

    Conclusion

    We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.

  • 46.
    Holmberg, Lars
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Granstrand, Bengt
    Ringberg, Anita
    Arnesson, Lars-Gunnar
    Sandelin, Kerstin
    Karlsson, Per
    Anderson, Harald
    Emdin, Stefan
    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. 1247-52Article 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.

  • 47.
    Høyer, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lambe, Mats
    Regionalt Cancer Center Uppsala Örebro, Uppsala University Hospital; Department of medical epidemiology och biostatistics, Karolinska Institutet.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lampic, Claudia
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
    Change in working time in a population-based cohort of patients with breast cancer2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 23, p. 2853-2860Article in journal (Refereed)
    Abstract [en]

    Purpose:

    We examined changes in working time 16 months after a breast cancer diagnosis and identified factors associated with job discontinuation and/or decreased working time.

    Patients and Methods:

    This was a population-based cohort study with 735 patients identified in the Regional Breast Cancer Quality Register of Central Sweden. The study sample consisted of 505 women (age <63 years at diagnosis) who completed questionnaires at baseline and at follow-up (on average 4 and 16 months after diagnosis, respectively). Clinical register data and questionnaire data on sociodemographic factors were obtained at baseline. Self-reported work-related data were obtained at follow-up. Odds ratios were estimated by using logistic regression models.

    Results:

    Compared with prediagnosis working time, 72% reported no change in working time, 2% reported an increase, 15% reported a decrease, and 11% did not work at follow-up. Chemotherapy increased the likelihood (odds ratio [OR], 2.45; 95% CI, 1.38 to 4.34) of job discontinuation/decreased working time. Among chemotherapy recipients, associated factors included full-time work prediagnosis (OR, 3.25; 95% CI, 1.51 to 7.01), cancer-related work limitations (OR, 5.26; 95% CI, 2.30 to 12.03), and less value attached to work (OR, 3.69; 95% CI, 1.80 to 7.54). In the nonchemotherapy group, older age (OR, 1.09; 95% CI, 1.02 to 1.17) and less value attached to work (OR, 5.00; 95% CI, 2.01 to 12.45) were associated with the outcome.

    Conclusion:

    The majority of women treated for breast cancer returned to their prediagnosis working time. Chemotherapy and cancer-related work limitations are important factors to take into account in identifying women in need of support. Moreover, it is important to consider the woman’s own valuation of labor market participation.

  • 48. Iveson, Timothy
    et al.
    Kerr, Rachel
    Saunders, Mark P.
    Waterston, Ashita Marie
    Hollander, Niels Henrik
    Medley, Louise C.
    Tabernero, Josep
    Wilson, Charles
    Ellis, Richard
    Essapen, Sharadah
    Haydon, Andrew Mark
    Dhadda, Amandeep Singh
    Hughes, Robert
    Falk, Stephen
    Abdel-Raouf, Sherif
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Allan, Karen
    Barlow, Winnie
    Briggs, Andrew
    Paul, James
    Toxicity and quality of life data from SCOT: An international phase III randomized (1:1) noninferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy.2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15Article in journal (Other academic)
  • 49.
    Jansson, Fredrik
    et al.
    Karolinska Inst, Stockholm, Sweden;Danderyd Hosp, Stockholm, Sweden.
    Drevin, Linda
    Reg Canc Ctr, Uppsala, Sweden.
    Frisell, Thomas
    Karolinska Inst, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Uppsala Univ Hosp, Uppsala, Sweden.
    Bratt, Ola
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden.
    Akre, Olof
    Karolinska Inst, Stockholm, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 18, p. 1847-1852Article in journal (Refereed)
    Abstract [en]

    Purpose: Prostate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation.

    Methods:We identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers)

    Results: Among monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar.

    Conclusion: Non-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.

  • 50.
    Jansson, Fredrik
    et al.
    Karolinska Inst, Stockholm, Sweden;Danderyd Hosp, Stockholm, Sweden.
    Drevin, Linda
    Reg Canc Ctr, Uppsala, Sweden.
    Frisell, Thomas
    Karolinska Inst, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Uppsala Univ Hosp, Uppsala, Sweden.
    Bratt, Ola
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden.
    Akre, Olof
    Karolinska Inst, Stockholm, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 18, p. 1847-+Article in journal (Refereed)
    Abstract [en]

    PurposeProstate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation.MethodsWe identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers)ResultsAmong monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar.ConclusionNon-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.

123 1 - 50 of 118
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