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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
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
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
Wang, S. S., Carrington, M., Berndt, S. I., Slager, S. L., Bracci, P. M., Voutsinas, J., . . . Skibola, C. F. (2018). HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes. Cancer Research, 78(14), 4086-4096
Open this publication in new window or tab >>HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
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2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 14, p. 4086-4096Article in journal (Refereed) Published
Abstract [en]

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-362009 (URN)10.1158/0008-5472.CAN-17-2900 (DOI)000439199100028 ()29735552 (PubMedID)
Funder
Swedish Cancer Society, 2009/659 02 6661Stockholm County Council, 20110209
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-05Bibliographically approved
Elander, N. O., Aughton, K., Ghaneh, P., Neoptolemos, J. P., Palmer, D. H., Cox, T. F., . . . Greenhalf, W. (2018). Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy. British Journal of Cancer, 118(8), 1084-1088
Open this publication in new window or tab >>Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy
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2018 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, no 8, p. 1084-1088Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma.

METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups.

RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group.

CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-352699 (URN)10.1038/s41416-018-0005-1 (DOI)000430080700009 ()29523831 (PubMedID)
Funder
Region Östergötland, LIO-418581Region Östergötland, LIO-338111
Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically approved
Sclafani, F., Chau, I., Cunningham, D., Hahne, J. C., Vlachogiannis, G., Eltahir, Z., . . . Valeri, N. (2018). KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer. Scientific Reports, 8, Article ID 1445.
Open this publication in new window or tab >>KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1445Article in journal (Refereed) Published
Abstract [en]

There are limited data on circulating, cell-free, tumour (ct) DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd) PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX +/- cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-343671 (URN)10.1038/s41598-018-19212-5 (DOI)000423045400018 ()29362371 (PubMedID)
Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-03-07Bibliographically approved
Glimelius, B. (2018). More than 1000 new manuscripts in 2017. Acta Oncologica, 57(2), 174-175
Open this publication in new window or tab >>More than 1000 new manuscripts in 2017
2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 174-175Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-350118 (URN)10.1080/0284186X.2017.1423181 (DOI)000423473200001 ()29303398 (PubMedID)
Available from: 2018-05-07 Created: 2018-05-07 Last updated: 2018-05-07Bibliographically approved
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