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Elliot, A. H., Blomqvist, L., Sigurdsson, A., Martling, A., Johansson, H., Glimelius, B. & Nilsson, P. J. (2019). An audit of performance, interpretation, and influence of pretherapeutic MRI in rectal cancer: a Swedish population-based cohort study. Acta Radiologica, 60(8), 955-961
Open this publication in new window or tab >>An audit of performance, interpretation, and influence of pretherapeutic MRI in rectal cancer: a Swedish population-based cohort study
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2019 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, no 8, p. 955-961Article in journal (Refereed) Published
Abstract [en]

Background: The performance of magnetic resonance imaging (MRI) interpretation and communication of findings and its implication on treatment decisions has not fully been explored in rectal cancer.

Purpose: To investigate in a region the adherence to MRI protocol standards and the relation between MRI interpretation and selection to preoperative therapy in rectal cancer.

Material and Methods: Data on consecutive patients who underwent elective rectal cancer surgery in the region from January to June 2010 were obtained from the National Colorectal Cancer Registry. Pretherapeutic MRI images were re-evaluated. Agreement between the original reports and the re-evaluation was compared using Cohen's kappa coefficient.

Results: Among the 94 patients included, 81 (86%) had pretherapeutic MRI in accordance with defined imaging guidelines. In 34% of the original MR reports, data on extramural venous invasion (mrEMVI) and mrT category were not reported. Complete tumor staging was not possible because of missing data in 33 (35%) of the patients. The agreement between the original MR reports and the re-evaluation regarding tumor stage was moderate (kappa = 0.48). For decided treatment compared to recommended preoperative treatment according to the re-evaluation, the agreement was fair (kappa = 0.33).

Conclusion: Established MRI protocol standards were not universally applied. Missing data and inadequacies in original MRI reports resulted in moderate agreement between the original report and the re-evaluation indicating a risk of inappropriate treatment selection. The results call for further educational efforts in rectal cancer MRI acquisition and repeated audits of image protocol adherence and interpretation quality.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2019
Keywords
Rectal cancer, MRI, radiotherapy, report quality, reader agreement
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-391290 (URN)10.1177/0284185118806638 (DOI)000476723700004 ()30322292 (PubMedID)
Funder
Stockholm County CouncilThe Cancer Society in Stockholm
Available from: 2019-08-22 Created: 2019-08-22 Last updated: 2019-08-22Bibliographically approved
Aasebö, K. Ö., Dragomir, A., Sundström, M., Mezheyeuski, A., Edqvist, P.-H. D., Eide, G. E., . . . Sorbye, H. (2019). Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients. Cancer Medicine, 8(7), 3623-3635
Open this publication in new window or tab >>Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients
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2019 (English)In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 7, p. 3623-3635Article in journal (Refereed) Published
Abstract [en]

Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.

Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.

Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).

Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
colorectal neoplasm, microsatellite instability, proto-oncogene proteins, B-raf, prognosis, neoplasm metastasis, KRAS protein
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-391954 (URN)10.1002/cam4.2205 (DOI)000477017100030 ()31070306 (PubMedID)
Funder
Erik, Karin och Gösta Selanders FoundationSwedish Cancer Society
Available from: 2019-08-27 Created: 2019-08-27 Last updated: 2019-08-27Bibliographically approved
Hammarström, K., Imam, I., Korsavidou Hult, N., Ekström, J., Sjöblom, T. & Glimelius, B. (2019). Determining the use of preoperative (chemo)radiotherapy in primary rectal cancer according to national and international guidelines. Radiotherapy and Oncology, 136, 106-112
Open this publication in new window or tab >>Determining the use of preoperative (chemo)radiotherapy in primary rectal cancer according to national and international guidelines
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2019 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 136, p. 106-112Article in journal (Refereed) Published
Abstract [en]

Background: Pre-operative radiotherapy (RT) or chemoradiotherapy (CRT) is frequently used prior to rectal cancer surgery to improve local control and survival. The treatment is administered according to guidelines, but these recommendations vary significantly between countries. Based on the stage distribution and risk factors of rectal cancers as determined by magnetic resonance imaging (MRI) in an unselected Swedish population, the use of RT/CRT according to 15 selected guidelines is described. Materials and methods: Selected guidelines from different countries and regions were applied to a wellcharacterized unselected population-based material of 686 primary non-metastatic rectal cancers staged by MRI. The fraction of patients assigned to surgery alone or surgery following pre-treatment with (C) RT was determined according to the respective guideline. RT/CRT administered to rectal cancer patients for other reasons, for example, for organ preservation or palliation, was not considered. Results: The fraction of patients with a clear recommendation for pre-treatment with (C) RT varied between 38% and 77% according to the different guidelines. In most guidelines, CRT was recommended to all patients who were not operated directly, and, in others, short-course RT was also recommended to patients with intermediate risk tumours. If only non-resectable or difficult to resect tumours were recommended pre-treatment, as stated in many Japanese publications, 9% would receive CRT followed by a delay to surgery. Conclusions: According to most guidelines, well over 50% of primary non-metastatic rectal cancer patients from a general population, in which screening for colorectal cancer is not practised, are recommended treatment with pre-operative/neo-adjuvant therapy. (C) 2019 Elsevier B. V. All rights reserved. Radiotherapy and Oncology

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2019
Keywords
Rectal cancer, Radiotherapy, Chemoradiotherapy, Clinical guidelines
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-390807 (URN)10.1016/j.radonc.2019.03.036 (DOI)000472490500015 ()31015111 (PubMedID)
Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2019-08-19Bibliographically approved
Glimelius, B. & Nygren, P. (2019). Lessons learned from the maturation of a cancer drug: oxaliplatin in colorectal cancer. Acta Oncologica, 58(4), 395-397
Open this publication in new window or tab >>Lessons learned from the maturation of a cancer drug: oxaliplatin in colorectal cancer
2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 4, p. 395-397Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-382767 (URN)10.1080/0284186X.2019.1584405 (DOI)000463726300001 ()30882261 (PubMedID)
Available from: 2019-05-03 Created: 2019-05-03 Last updated: 2019-05-03Bibliographically approved
Erlandsson, J., Pettersson, D., Glimelius, B., Holm, T. & Martling, A. (2019). Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy. British Journal of Surgery, 106(9), 1248-1256
Open this publication in new window or tab >>Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy
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2019 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, no 9, p. 1248-1256Article in journal (Refereed) Published
Abstract [en]

Background: The optimal timing of surgery for rectal cancer after radiotherapy (RT) is disputed. The Stockholm III trial concluded that it was oncologically safe to delay surgery for 4-8weeks after short-course RT (SRT), with fewer postoperative complications compared with SRT with surgery within a week. Other studies have indicated that an even shorter interval between RT and surgery (0-3 days) might be beneficial. The aim of this study was to identify the optimal interval to surgery after RT.

Methods: Patients were analysed as treated, in terms of overall treatment time (OTT), the interval from the start of RT until the day of surgery. Patients receiving SRT (5x5Gy) were categorized according to OTT: 7 days (group A), 8-13 days (group B), 5-7weeks (group C) and 8-13weeks (group D). Patients receiving long-course RT (25x2Gy) were grouped into those with an OTT of 9-11weeks (group E) or 12-14weeks (group F). Outcomes assessed were postoperative complications and early mortality.

Results: A total of 810 patients were analysed (group A, 100; group B, 247; group C, 192; group D, 160; group E, 52; group F, 59). Baseline patient characteristics were similar. There were significantly more overall complications in group B than in groups C and D. Adjusted odds ratios, with B as the reference group, were: 0.72 (95 per cent c. i. 0.40 to 1.32; P = 0.289), 0.50 (0.30 to 0.84; P = 0.009) and 0.39 (0.23 to 0.65; P < 0.001) for groups A, C and D respectively. Early mortality was similar in all groups. There were no significant differences between long-course RT groups.

Conclusion: These results suggest that surgery should optimally be delayed for 4-12weeks (OTT 5-13weeks) after SRT.

Place, publisher, year, edition, pages
WILEY, 2019
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-390494 (URN)10.1002/bjs.11200 (DOI)000475506700019 ()31197822 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyThe Cancer Society in StockholmStockholm County Council
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved
Gargiulo, P., Dietrich, D., Herrmann, R., Bodoky, G., Ruhstaller, T., Scheithauer, W., . . . Brauchli, P. (2019). Predicting mortality and adverse events in patients with advanced pancreatic cancer treated with palliative gemcitabine-based chemotherapy in a multicentre phase III randomized clinical trial: the APC-SAKK risk scores. THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 11, Article ID UNSP 1758835918818351.
Open this publication in new window or tab >>Predicting mortality and adverse events in patients with advanced pancreatic cancer treated with palliative gemcitabine-based chemotherapy in a multicentre phase III randomized clinical trial: the APC-SAKK risk scores
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2019 (English)In: THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, ISSN 1758-8340, Vol. 11, article id UNSP 1758835918818351Article in journal (Refereed) Published
Abstract [en]

Background: The prognosis of advanced pancreatic cancer (APC) is poor and differs considerably among patients. Therefore, it is clinically relevant to identify patients with APC who are more likely to benefit from palliative chemotherapy with reduced risk of toxicity. To date, there is no prognostic score universally recommended to help clinicians in planning the therapeutic management. Methods: Using individual patient data from 319 cases of APC treated with gemcitabine-based chemotherapy and enrolled in the SAKK 44/00-CECOG/PAN.1.3.001 randomized trial, several baseline variables, including inflammatory markers, were analysed post hoc as predictors of mortality and/or grade 3 or 4 chemotherapy-related toxicity and separate risk scores were developed. Results: Median survival of the study patients was 7.9 months (interquartile range 3.7-13.3 months). Independent predictors of mortality included increased Aspartate transaminase (ASAT), low performance status, increased derived neutrophil to lymphocyte ratio, increased Carbohydrate Antigen 19-9 (CA 19-9), low haemoglobin, presence of pain, presence of metastasis and increased alkaline phosphatase (ALP). During the study, 117 patients experienced at least one grade 3 or 4 adverse event. Independent predictors of toxicity included white blood cells, ALP, renal function and bilirubin levels at baseline. Both models displayed moderate levels of discrimination (C-statistic 0.68 and 0.64 for mortality and toxicity, respectively) and adequate calibration. Conclusions: We developed simple-to-use prognostic scores for mortality and severe toxicity for patients with APC. These scores can be useful in daily practice to identify patients with increased risk of death or toxicity and to plan the most appropriate therapeutic strategy to improve survival and quality of life. Further prospective studies to validate such scores are needed.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2019
Keywords
advanced pancreatic cancer, chemotherapy, inflammatory markers, mortality, prediction score, toxicity
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-393016 (URN)10.1177/1758835918818351 (DOI)000478869000001 ()30636977 (PubMedID)
Available from: 2019-09-19 Created: 2019-09-19 Last updated: 2019-09-19Bibliographically approved
Whither, S. B., Liposits, G., Skuladottir, H., Hofsli, E., Shah, C.-H., Poulsen, L. Ö., . . . Pfeiffer, P. (2019). Reduced-dose combination chemotherapy (S-1 plus oxaliplatin) versus full- dose monotherapy (S-1) in older vulnerable patients with metastatic colorectal cancer (NORDIC9): a randomised, open-label phase 2 trial. The Lancet Gastroenterology & Hepatology, 4(5), 376-388
Open this publication in new window or tab >>Reduced-dose combination chemotherapy (S-1 plus oxaliplatin) versus full- dose monotherapy (S-1) in older vulnerable patients with metastatic colorectal cancer (NORDIC9): a randomised, open-label phase 2 trial
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2019 (English)In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 4, no 5, p. 376-388Article in journal (Refereed) Published
Abstract [en]

Background: Older or vulnerable patients with metastatic colorectal cancer are seldom included in randomised trials.The multicentre NORDIC9 trial evaluated reduced-dose combination chemotherapy compared with full-dose monotherapy in older, vulnerable patients.

Methods: This randomised, open-label phase 2 trial was done in 23 Nordic oncology clinics and included patients aged 70 years or older with previously untreated metastatic colorectal cancer who were not candidates for full-dose combination chemotherapy. Patients were block randomised (1: 1) using a web-based tool to full-dose S-1 (30 mg/m(2) orally twice daily on days 1-14 every 3 weeks) followed by second-line treatment at progression with irinotecan (250 mg/m(2) intravenously on day 1 every 3 weeks or 180 mg/m(2) intravenously on day 1 every 2 weeks) or reduceddose combination chemotherapy with S-1 (20 mg/m(2) orally twice daily on days 1-14) and oxaliplatin (100 mg/m(2) intravenously on day 1 every 3 weeks) followed by second-line treatment at progression with S-1 (20 mg/m(2) orally twice daily on days 1-14) and irinotecan (180 mg/m(2) intravenously on day 1 every 3 weeks). Use of bevacizumab (7.5 mg/kg intravenously on day 1 of each cycle) was optional. Treatment allocation was not masked and randomisation was stratified for institution and bevacizumab. The primary outcome was progression-free survival. Survival analyses were by intention to treat and safety analyses were done on the treated population. This trial is registered with EudraCT, number 2014-000394-39, and is closed to new participants.

Findings: From March 9, 2015, to Oct 11, 2017, 160 patients with a median age of 78 years (IQR 76-81) were randomly assigned to full-dose monotherapy (n=83) or reduced-dose combination chemotherapy (n=77). At data cutoff (Sept 1, 2018; median follow-up 23.8 months [IQR 18.8-30.9]), 81 (98%) patients in the full-dose monotherapy group and 71 (92%) patients in the reduced-dose combination group had progressed or died. Median progression-free survival was significantly longer with reduced-dose combination chemotherapy (6.2 months [95% CI 5.3-8.3]) than with full-dose monotherapy (5.3 months [4.1-6.8]; hazard ratio [HR] 0.72 [95% CI 0.52-0.99]; p=0.047). Toxicity was evaluated in 157 patients who received treatment. Significantly more patients in the full-dose monotherapy group (51 [62%] of 82 patients) experienced at least one grade 3-4 adverse event than in the reduced-dose combination group (32 [43%] of 75 patients; p=0.014). Grade 3-4 diarrhoea (12 [15%] vs two [3%]; p=0.018), fatigue (ten [12%] vs three [4%]; p=0.083), and dehydration (five [6%] vs none; p=0.060) were more frequent in the full-dose monotherapy group than in the reduced-dose combination group. Treatment-related deaths occurred in three patients during firstline treatment and three patients during second-line treatment (two in the full-dose monotherapy group vs one in the reduced-dose combination group in both cases).

Interpretation: Reduced-dose combination chemotherapy with S-1 and oxaliplatin for older, vulnerable patients with metastatic colorectal cancer was more effective and resulted in less toxicity than full-dose monotherapy with S-1. Reduced-dose combination chemotherapy could be a preferred treatment for this population.

Place, publisher, year, edition, pages
ELSEVIER INC, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-382373 (URN)10.1016/S2468-1253(19)30041-X (DOI)000463786300023 ()30852136 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-04-26Bibliographically approved
Mezheyeuski, A., Hrynchyk, I., Herrera, M., Karlberg, M., Osterman, E., Ragnhammar, P., . . . Ostman, A. (2019). Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer. British Journal of Cancer, 121(4), 303-311
Open this publication in new window or tab >>Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer
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2019 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 121, no 4, p. 303-311Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task. METHODS: Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area. RESULTS: High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051). CONCLUSION: Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-393661 (URN)10.1038/s41416-019-0519-1 (DOI)000480675100003 ()31289351 (PubMedID)
Funder
The Cancer Research Funds of RadiumhemmetSwedish Research Council
Available from: 2019-09-25 Created: 2019-09-25 Last updated: 2019-09-25Bibliographically approved
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
Ghaneh, P., Kleeff, J., Halloran, C. M., Raraty, M., Jackson, R., Melling, J., . . . Neoptolemos, J. P. (2019). The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma. Annals of Surgery, 269(3), 520-529
Open this publication in new window or tab >>The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma
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2019 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 269, no 3, p. 520-529Article in journal (Refereed) Published
Abstract [en]

Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies

Methods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.

Results: There were 1151 patients, of whom 505 (43.9%) had an RI resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative R0 >1 mm) tumors, 25.4 (21.6 30.4) months for 146 (12.7%) patients with RI <1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R 1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥ 1, maximum tumor size, and RI-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status. WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.

Conclusions: RI-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

Keywords
pancreatic cancer, recurrence, resection margins, surgery, survival
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-383878 (URN)10.1097/SLA.0000000000002557 (DOI)000467458600036 ()29068800 (PubMedID)
Funder
AstraZeneca
Available from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5440-791x

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