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Majano, S. B., Di Girolamo, C., Rachet, B., Maringe, C., Guren, M. G., Glimelius, B., . . . Walters, S. (2019). Surgical treatment and survival from colorectal cancer in Denmark, England, Norway, and Sweden: a population-based study. The Lancet Oncology, 20(1), 74-87
Open this publication in new window or tab >>Surgical treatment and survival from colorectal cancer in Denmark, England, Norway, and Sweden: a population-based study
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2019 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 20, no 1, p. 74-87Article in journal (Refereed) Published
Abstract [en]

Background Survival from colorectal cancer has been shown to be lower in Denmark and England than in comparable high-income countries. We used data from national colorectal cancer registries to assess whether differences in the proportion of patients receiving resectional surgery could contribute to international differences in colorectal cancer survival.

Methods In this population-based study, we collected data from all patients aged 18-99 years diagnosed with primary, invasive, colorectal adenocarcinoma from Jan 1, 2010, to Dec 31, 2012, in Denmark, England, Norway, and Sweden, from national colorectal cancer registries. We estimated age-standardised net survival using multivariable modelling, and we compared the proportion of patients receiving resectional surgery by stage and age. We used logistic regression to predict the resectional surgery status patients would have had if they had been treated as in the best performing country, given their individual characteristics.

Findings We extracted registry data for 139457 adult patients with invasive colorectal adenocarcinoma: 12958 patients in Denmark, 97466 in England, 11450 in Norway, and 17583 in Sweden. 3-year colon cancer survival was lower in England (63.9%, 95% CI 63.5-64.3) and Denmark (65.7%, 64.7-66.8) than in Norway (69.5%, 68.4-70.5) and Sweden (72.1%, 71.2-73.0). Rectal cancer survival was lower in England (69.7%, 69.1-70.3) than in the other three countries (Denmark 72.5%, 71.1-74.0; Sweden 74.1%, 72.7-75.4; and Norway 75.0%, 73.1-76.8). We found no significant differences in survival for patients with stage I disease in any of the four countries. 3-year survival after stage II or III rectal cancer and stage IV colon cancer was consistently lower in England (stage II rectal cancer 86.4%, 95% CI 85.0-87.6; stage III rectal cancer 75.5%, 74.2-76.7; and stage IV colon cancer 20.5%, 19.9-21.1) than in Norway (94.1%, 91.5-96.0; 83.4%, 80.1-86.1; and 33.0%, 31.0-35.1) and Sweden (92.9%, 90.8-94.6; 80.6%, 78.2-82.7; and 23.7%, 22.0-25.3). 3-year survival after stage II rectal cancer and stage IV colon cancer was also lower in England than in Denmark (stage II rectal cancer 91.2%, 88.8-93.1; and stage IV colon cancer 23.5%, 21.9-25.1). The total proportion of patients treated with resectional surgery ranged from 47803 (68.4%) of 69867 patients in England to 9582 (81.3%) of 11786 in Sweden for colon cancer, and from 16544 (59.9%) of 27599 in England to 4106 (70.8%) of 5797 in Sweden for rectal cancer. This range was widest for patients older than 75 years (colon cancer 19078 [59.7%] of 31946 patients in England to 4429 [80.9%] of 5474 in Sweden; rectal cancer 4663 [45.7%] of 10195 in England to 1342 [61.9%] of 2169 in Sweden), and the proportion of patients treated with resectional surgery was consistently lowest in England. The age gradient of the decline in the proportion of patients treated with resectional surgery was steeper in England than in the other three countries in all stage categories. In the hypothetical scenario where all patients were treated as in Sweden, given their age, sex, and disease stage, the largest increase in resectional surgery would be for patients with stage III rectal cancer in England (increasing from 70.3% to 88.2%).

Interpretation Survival from colon cancer and rectal cancer in England and colon cancer in Denmark was lower than in Norway and Sweden. Survival paralleled the relative provision of resectional surgery in these countries. Differences in patient selection for surgery, especially in patients older than 75 years or individuals with advanced disease, might partly explain these differences in international colorectal cancer survival.

Keywords
complete mesocolic excision, rectal-cancer, adjuvant chemotherapy, older patients, surgery, diagnosis, radiotherapy, metaanalysis, management, registries
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-374440 (URN)10.1016/S1470-2045(18)30646-6 (DOI)000454901700047 ()30545752 (PubMedID)
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-01-24Bibliographically approved
Iveson, T. J., Kerr, R. S., Saunders, M. P., Cassidy, J., Henrik Hollander, N., Tabernero, J., . . . Paul, J. (2018). 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. The Lancet Oncology, 19(4), 562-578
Open this publication in new window or tab >>3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial
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2018 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 19, no 4, p. 562-578Article in journal (Refereed) Published
Abstract [en]

Background: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.

Methods: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1: 1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1.13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.

Findings: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76.7% (95% CI 75.1-78.2) for the 3 month group and 77.1% (75.6-78.6) for the 6 month group, giving a hazard ratio of 1.006 (0.909-1.114, test for non-inferiority p=0.012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).

Interpretation: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-353105 (URN)10.1016/S1470-2045(18)30093-7 (DOI)000428790400043 ()29611518 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-06-20 Created: 2018-06-20 Last updated: 2018-06-20Bibliographically approved
Babaei, M., Balavarca, Y., Jansen, L., Lemmens, V., van Erning, F. N., van Eycken, L., . . . Brenner, H. (2018). Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study. International Journal of Cancer, 142(7), 1480-1489
Open this publication in new window or tab >>Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 7, p. 1480-1489Article in journal (Refereed) Published
Abstract [en]

The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients. We investigated the administration of ACT and its association with overall survival in resected Stage II (overall and stratified by low-/high-risk) and Stage III colon cancer patients in three European countries including The Netherlands (2009-2014), Belgium (2009-2013) and Sweden (2009-2014). Hazard ratios (HR) for death were obtained by Cox regression models adjusted for potential confounders. A total of 60244 resected colon cancer patients with pathological Stages II and III were analyzed. A small proportion (range 9-24%) of Stage II and over half (range 55-68%) of Stage III patients received ACT. Administration of ACT in Stages II and III tumors decreased with higher age of patients. Administration of ACT was significantly associated with higher overall survival in high-risk Stage II patients (in The Netherlands (HR; 95%CI = 0.82 (0.67-0.99), Belgium (0.73; 0.59-0.90) and Sweden (0.58; 0.44-0.75)), and in Stage III patients (in The Netherlands (0.47; 0.43-0.50), Belgium (0.46; 0.41-0.50) and Sweden (0.48; 0.43-0.54)). In Stage III, results were consistent across subgroups including elderly patients. Our results show an association of ACT with higher survival among Stage III and high-risk Stage II colon cancer patients. Further investigations are needed on the selection criteria of Stages II and III colon cancer patients for ACT.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
colon cancer, adjuvant chemotherapy, variations, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346647 (URN)10.1002/ijc.31168 (DOI)000424635000019 ()29159866 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 260791
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Kleinstern, G., Camp, N. J., Goldin, L. R., Vachon, C. M., Vajdic, C. M., de Sanjose, S., . . . Slager, S. L. (2018). Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Blood, 131(23), 2541-2551
Open this publication in new window or tab >>Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
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2018 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 131, no 23, p. 2541-2551Article in journal (Refereed) Published
Abstract [en]

Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4x10(-94)). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 x 10(-30)) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 x10(-16)). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.

Place, publisher, year, edition, pages
AMER SOC HEMATOLOGY, 2018
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-358155 (URN)10.1182/blood-2017-11-814608 (DOI)000434789800005 ()29674426 (PubMedID)
Funder
NIH (National Institute of Health)Swedish Cancer Society, 2009/659Swedish Cancer Society, 02 6661
Available from: 2018-12-04 Created: 2018-12-04 Last updated: 2018-12-04Bibliographically approved
Goey, K. K. H., Sorbye, H., Glimelius, B., Adams, R. A., Andre, T., Arnold, D., . . . Koopman, M. (2018). Consensus statement on essential patient characteristics in systemic treatment trials for metastatic colorectal cancer: Supported by the ARCAD Group. European Journal of Cancer, 100, 35-45
Open this publication in new window or tab >>Consensus statement on essential patient characteristics in systemic treatment trials for metastatic colorectal cancer: Supported by the ARCAD Group
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2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 100, p. 35-45Article in journal (Refereed) Published
Abstract [en]

Background: Patient characteristics and stratification factors are key features influencing trial outcomes. However, there is substantial heterogeneity in reporting of patient characteristics and use of stratification factors in phase 3 trials investigating systemic treatment of metastatic colorectal cancer (mCRC). We aimed to develop a minimum set of essential baseline characteristics and stratification factors to include in such trials. Methods: We performed a modified, two-round Delphi survey among international experts with wide experience in the conduct and methodology of phase 3 trials of systemic treatment of mCRC. Results: Thirty mCRC experts from 15 different countries completed both consensus rounds. A total of 14 patient characteristics were included in the recommended set: age, performance status, primary tumour location, primary tumour resection, prior chemotherapy, number of metastatic sites, liver-only disease, liver involvement, surgical resection of metastases, synchronous versus metachronous metastases, (K)RAS and BRAF mutation status, microsatellite instability/mismatch repair status and number of prior treatment lines. A total of five patient characteristics were considered the most relevant stratification factors: RAS/BRAF mutation status, performance status, primary tumour sidedness and liver-only disease. Conclusions: This survey provides a minimum set of essential baseline patient characteristics and stratification factors to include in phase 3 trials of systemic treatment of mCRC. Inclusion of these patient characteristics and strata in study protocols and final study reports will improve interpretation of trial results and facilitate cross-study comparisons.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Colorectal cancer, Metastatic disease, Patient characteristics, Prognosis, Stratification, Clinical trials, Delphi survey
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-361483 (URN)10.1016/j.ejca.2018.05.010 (DOI)000439473900005 ()29936065 (PubMedID)
Available from: 2018-09-27 Created: 2018-09-27 Last updated: 2018-09-27Bibliographically approved
ter Veer, E., van Rijssen, L. B., Besselink, M. G., Mali, R. M. A., Berlin, J. D., Boeck, S., . . . van Laarhoven, H. W. M. (2018). Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. The Lancet Oncology, 19(3), E151-E160
Open this publication in new window or tab >>Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease
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2018 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 19, no 3, p. E151-E160Article, review/survey (Refereed) Published
Abstract [en]

Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-352928 (URN)10.1016/S1470-2045(18)30098-6 (DOI)000426466100027 ()29508762 (PubMedID)
Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically approved
Glimelius, B. & Pfeiffer, P. (2018). Do we make progress in elderly patients with metastatic colorectal cancer?. Acta Oncologica, 57(11), 1422-1426
Open this publication in new window or tab >>Do we make progress in elderly patients with metastatic colorectal cancer?
2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 11, p. 1422-1426Article in journal, Editorial material (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-372516 (URN)10.1080/0284186X.2018.1535189 (DOI)000451615600001 ()30384805 (PubMedID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Kalter, J., Verdonck-de Leeuw, I. M., Sweegers, M. G., Aaronson, N. K., Jacobsen, P. B., Newton, R. U., . . . Buffart, L. M. (2018). Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs. Psycho-Oncology, 27(4), 1150-1161
Open this publication in new window or tab >>Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs
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2018 (English)In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 27, no 4, p. 1150-1161Article, review/survey (Refereed) Published
Abstract [en]

Objective: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. Methods: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (=0.14,95%CI=0.06;0.21), EF ( beta = 0.13,95%CI = 0.05;0.20), and SF (beta = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
coping skills training, individual patient data meta-analysis, neoplasm, psychosocial care, psychotherapy, quality of life
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-357487 (URN)10.1002/pon.4648 (DOI)000430230400007 ()29361206 (PubMedID)
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Larsson, A., Karnevi, E., Nodin, B., Sorbye, H., Dragomir, A., Pfeiffer, P., . . . Ponten, F. (2018). Expression of podocalyxin-like protein and epidermal growth factor receptor in metastatic colorectal cancer: Prognostic impact and relationship with response to cetuximab.. In: : . Paper presented at ASCO 2018.
Open this publication in new window or tab >>Expression of podocalyxin-like protein and epidermal growth factor receptor in metastatic colorectal cancer: Prognostic impact and relationship with response to cetuximab.
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-365898 (URN)
Conference
ASCO 2018
Available from: 2018-11-14 Created: 2018-11-14 Last updated: 2018-11-14
Glimelius, B. (2018). Forty-five years in oncology, 25 years with Acta Oncologica. Acta Oncologica, 57(12), 1593-1598
Open this publication in new window or tab >>Forty-five years in oncology, 25 years with Acta Oncologica
2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 12, p. 1593-1598Article in journal, Editorial material (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-373917 (URN)10.1080/0284186X.2018.1547841 (DOI)000453867800001 ()30489167 (PubMedID)
Available from: 2019-01-17 Created: 2019-01-17 Last updated: 2019-01-17Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-5440-791x

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