| 1. |
- Mezheyeuski, Artur, et al.
(författare)
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Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer
- 2018
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Ingår i: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 472:3, s. 395-405
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Tidskriftsartikel (refereegranskat)abstract
- Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated that the survival associations occurred among cases that received 5-FU+oxaliplatin combination treatment, but not in patients receiving 5-FU +/- irinotecan. The finding was validated by analyses of the independent cohort. In summary, previously unreported stromal expression of claudin-2 in CAFs of human CRC was detected together with significant association between high claudin-2 expression in CAFs and shorter survival in 5-FU+oxaliplatin-treated mCRC patients.
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| 2. |
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| 3. |
- Brooke, Hannah L, et al.
(författare)
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Socioeconomic position and incidence of colorectal cancer in the Swedish population.
- 2016
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 40, s. 188-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The association between socioeconomic position and incidence of colorectal cancer is inconsistent and differs by global region. We aimed to clarify this association in the Swedish population.METHODS: We conducted a population-based open cohort study using data from Swedish national registers. We included all individuals, aged ≥30 years, residing in Sweden between 1993 and 2010. Socioeconomic position was indicated by (1) highest educational level (five groups), and (2) disposable income (quintiles). We used Poisson regression to estimate incidence rate ratios (IRR) and 95% confidence intervals (95% CI) of colon and rectal cancer, and colon and rectal dysplasia.RESULTS: In total, 97,827,817 person-years were accumulated and 82,686 cases of colorectal cancer were diagnosed. Compared to men with 'higher secondary' education, the adjusted IRRs (95% CI) of rectal cancer in men with 'primary or less', 'lower secondary', 'lower university' or 'higher university' education were: 1.06 (1.00, 1.11), 1.05 (0.99, 1.10), 0.96 (0.89, 1.03), and 0.92 (0.86, 0.98), respectively. In women, the corresponding figures were: 1.04 (0.95, 1.14), 1.03 (0.94, 1.13), 0.92 (0.82, 1.02) and 0.92 (0.82, 1.02). Disposable income was not associated with rectal cancer incidence. Adjusted IRRs of colon cancer did not differ between levels of education or disposable income overall or for specific colon sub-sites. Neither education nor disposable income was consistently associated with incidence of colon or rectal dysplasia.CONCLUSIONS: Prevention strategies for colon cancer should be applicable to individuals regardless of their socioeconomic position. However, factors conferred by education, e.g., health awareness, may be important for approaches aiming to reduce inequalities in incidence of rectal cancer. Further evaluation of cancer prevention and health promotion strategies among less educated groups is warranted.
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| 4. |
- Chen, Lingjing, et al.
(författare)
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Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register
- 2018
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Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 126:3, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- Aim: A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). Methods: We identified 14,901 rectal cancer patients diagnosed 1995-2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980-1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. Results: We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92-1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93-1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (lRR(register) = 1.41, 95% CI 1.15-2.72; IRRtrials = 1.41, 95% CI 0.97-2.04), that remained during the first 6 months following surgery among patients treated 2006-2009, after the introduction of antithrombotic treatment (IRR6 (months) = 2.30, 95% CI 1.01-5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Discussion: Preoperative radiotherapy did not affect rectal cancer patients' risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. (C) 2017 Elsevier B.V. All rights reserved.
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| 5. |
- Chen, Lingjing, et al.
(författare)
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Work Loss Duration and Predictors Following Rectal Cancer Treatment among Patients with and without Prediagnostic Work Loss
- 2016
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 25:6, s. 987-994
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Tidskriftsartikel (refereegranskat)abstract
- Background: The number of working-age rectal cancer survivors is increasing due to early detection and improved treatment. However, work loss duration and predictors among them have not been studied thoroughly. Methods: We identified 3,438 patients with stage I-III rectal cancer, 18 to 61 years of age in the Swedish Colorectal Cancer Register 1996-2009. Information on work loss due to sick leave or disability pension was collected from 2 years before diagnosis to 5 years after (until December 31st, 2013). Incidence rate ratios (IRR) of work loss were estimated in a negative binominal model by clinical characteristics for the 1st and 2nd-5th years after diagnosis. Patients were stratified by prediagnostic work loss. Results: Patients without prediagnostic work loss (74%) experienced median 147 days (25th and 75th percentile: 55 and 281) of work loss during the 1st year after diagnosis. Work loss rates (2nd-5th years) were significantly increased among relapse-free patients diagnosed in stage III [IRR = 1.92; 95% confidence interval (CI), 1.52-2.43], operated with abdominoperineal resection (IRR = 1.26; 95% CI, 1.03-1.56), and treated with neoadjuvant (chemo) radiotherapy (IRR = 1.46; 95% CI, 1.06-2.02). Patients with prediagnostic work loss (26%) experienced median 336 days (25th and 75th percentile: 183 and 365) of work loss during the 1st year, and rates did not vary clinically till 5 years. Conclusion: Without prediagnostic work loss, disease-and treatment-related factors could help identify rectal cancer patients in need of early interventions to facilitate return to work. Impact: Clinical awareness around prediagnostic and postdiagnostic work loss and individualized cancer rehabilitation programs should be emphasized among cancer survivors.
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| 6. |
- Claassen, Yvette H. M., et al.
(författare)
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Treatment and survival of rectal cancer patients over the age of 80 years : a EURECCA international comparison
- 2018
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 119:4, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+.METHODS: Patients of >= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients.RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO.CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.
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| 7. |
- Egenvall, Monika, et al.
(författare)
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Prediction of outcome after curative surgery for colorectal cancer : preoperative haemoglobin, C-reactive protein and albumin
- 2018
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 20:1, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim was to evaluate a scoring system using the values of preoperative haemoglobin, C-reactive protein (CRP) and serum albumin to predict colorectal cancer recurrence and survival.METHOD: Data on all curative resections for Stages I-III colorectal cancer performed at a tertiary referral hospital 2007-2010 have been recorded ion the Swedish Colorectal Cancer Registry and were matched to the local databases for laboratory results and blood transfusion. Patients who died within 30 days or during primary hospital admission were excluded. Preoperative haemoglobin, CRP and albumin levels were recorded for 417 patients. A score (0-3) was derived on presence of anaemia (Hb <120 g/l for women and <130 g/l for men), raised CRP (>10 mg/ml) and low albumin (<35g/dl). The risks for recurrence and impaired overall survival were assessed using Cox regression analyses.RESULTS: Impaired overall survival was found when one, two or three of the criteria, anaemia, elevated CRP and low albumin, were present prior to surgery (HR 3.61, 1.66-7.85; HR 3.91, 1.75-8.74; HR 4.85, 2.15-10.93, respectively). The risk for recurrence, however, was not related to the presence of these criteria.CONCLUSION: Overall survival after curative surgery for Stages I-III colorectal cancer is impaired when anaemia, elevated CRP or low albumin exist prior to surgery. This article is protected by copyright. All rights reserved.
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| 8. |
- Elliot, Anders H., et al.
(författare)
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An audit of performance, interpretation, and influence of pretherapeutic MRI in rectal cancer : a Swedish population-based cohort study
- 2019
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Ingår i: Acta Radiologica. - : SAGE PUBLICATIONS LTD. - 0284-1851 .- 1600-0455. ; 60:8, s. 955-961
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Erlandsson, Johan, et al.
(författare)
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Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial
- 2017
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Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 18:3, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- Background Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. Methods In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 x 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 x 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1.7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813. Findings Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33.4 months (range 18.2-62.2) in the short-course radiotherapy group and 19.3 months (8.5-39.5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33.3 months (range 17.8-114.3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1.44 [95% CI 0.41-5.11]; long-course radiotherapy with delay 2.24 [0.71-7.10]; p=0.48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (amp;lt;1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0.59 [95% CI 0.36-0.97], long-course radiotherapy with delay 0.63 [0.38-1.04], p=0.075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0.61 [95% CI 0.45-0.83] p=0.001). Interpretation Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery.
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| 10. |
- Erlandsson, Johan, et al.
(författare)
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Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial
- 2019
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Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 135, s. 178-186
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Neoadjuvant radiotherapy (RT) in rectal cancer induces tumour regression with a possible complete response (pCR). The optimal fractionation and timing to surgery is not established. The Stockholm III trial randomly assigned 840 patients to 5 x 5 Gy surgery within one week (SRT), 5 x 5 Gy with surgery after 4-8 weeks, and 2 Gy x 25 with surgery after 4-8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. Material and methods: All available microscopy slides were assessed by one pathologist, blinded to treatment, regarding tumour regression, graded according to the Dworak system (TRG), TNM-stage and other standard histopathology characteristics. Patients' data were collected from the Swedish ColoRectal Cancer Registry. Outcomes were TRG, pCR-rates, overall survival (OS) and time to recurrence (TTR). Results: 318, 285 and 94 patients were included in the SRT, SRT-delay and LRT-delay groups. Median follow up was 5.7 years. There were significantly lower tumour stages after SRT-delay. pCR was seen in 1 (0.3%), 29 (10.4%) and 2 (2.2%) patients in SRT, SRT-delay and LRT-delay, respectively. The pCR and Dworak grade 4 were associated with superior survival. pCR vs no-pCR Hazard Ratio (95% Confidence Interval) OS: 0.51 (0.26-0.99) p = 0.046, TTR: 0.27 (0.09-0.86) p = 0.027. Conclusion: SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 x 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR.
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