A qualitative stakeholder analysis of beliefs, facilitators, and barriers for a feasible prehabilitation program before lung cancer surgery.

BACKGROUND: In order to develop a feasible prehabilitation program before surgery of NSCLC, this study aimed to gain insight into beliefs, facilitators, and barriers of (1) healthcare professionals to refer patients to a prehabilitation program, (2) patients to participate in and adhere to a prehabilitation program, and (3) informal caregivers to support their loved ones. METHODS: Semi-structured interviews were conducted with healthcare professionals, patients who underwent surgery for NSCLC, and their informal caregivers. The capability, opportunity, and motivation for behavior-model (COM-B) guided the development of the interview questions. Results were analyzed thematically. RESULTS: The interviews were conducted with twelve healthcare professionals, seventeen patients, and sixteen informal caregivers. Four main themes were identified: (1) content of prehabilitation and referral, (2) organizational factors, (3) personal factors for participation, and (4) environmental factors. Healthcare professionals mentioned that multiple professionals should facilitate the referral of patients to prehabilitation within primary and secondary healthcare involved in prehabilitation, considering the short preoperative period. Patients did not know that a better preoperative physical fitness and nutritional status would make a difference in the risk of postoperative complications. Patients indicated that they want to receive information about the aim and possibilities of prehabilitation. Most patients preferred a group-based physical exercise training program organized in their living context in primary care. Informal caregivers could support their loved one when prehabilitation takes place by doing exercises together. CONCLUSION: A prehabilitation program should be started as soon as possible after the diagnosis of lung cancer. Receiving information about the purpose and effects of prehabilitation in a consult with a physician seems crucial to patients and informal caregivers to be involved in prehabilitation. Support of loved ones in the patient's own living context is essential for adherence to a prehabilitation program.

Evidence base for exercise prehabilitation suggests favourable outcomes for patients undergoing surgery for non-small cell lung cancer despite being of low therapeutic quality: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to evaluate whether exercise prehabilitation programs reduce postoperative complications, postoperative mortality, and length of hospital stay (LoS) in patients undergoing surgery for non-small cell lung cancer (NSCLC), thereby accounting for the quality of the physical exercise program. METHODS: Two reviewers independently selected randomized controlled trials (RCTs) and observational studies and assessed them for methodological quality and therapeutic quality of the exercise prehabilitation program (i-CONTENT tool). Eligible studies included patients with NSCLC performing exercise prehabilitation and reported the occurrence of 90-day postoperative complications, postoperative mortality, and LoS. Meta-analyses were performed and the certainty of the evidence was graded (Grading of Recommendations Assessment, Development and Evaluation (GRADE)) for each outcome. RESULTS: Sixteen studies, comprising 2,096 patients, were included. Pooled analyses of RCTs and observational studies showed that prehabilitation reduces postoperative pulmonary complications (OR 0.45), postoperative severe complications (OR 0.51), and LoS (mean difference -2.46 days), but not postoperative mortality (OR 1.11). The certainty of evidence was very low to moderate for all outcomes. Risk of ineffectiveness of the prehabilitation program was high in half of the studies due to an inadequate reporting of the dosage of the exercise program, inadequate type and timing of the outcome assessment, and low adherence. CONCLUSION: Although risk of ineffectiveness was high for half of the prehabilitation programs and certainty of evidence was very low to moderate, prehabilitation seems to result in a reduction of postoperative pulmonary and severe complications, as well as LoS in patients undergoing surgery for NSCLC.

Tumour-stroma ratio to predict pathological response to neo-adjuvant treatment in rectal cancer.

INTRODUCTION: Management of rectal cancer has advanced, with an increasing use of neoadjuvant chemoradiotherapy (nCRT). This opens options for organ preserving treatment for those with a major response to nCRT. However, the degree of clinical response, based on MRI and post-treatment biopsies, only poorly matches the degree of actual pathological response. In order to select patients with major pathological response without surgical resection, it is of importance to define tumour markers predicting the degree of pathological response to nCRT. The intra-tumoural tumour-stroma ratio (TSR) might be this marker. METHODS: TSR in pre-treatment biopsies was estimated according to the method described by van Pelt et al. The degree of pathological response was assessed on the tumour resection according to tumour regression grading (TRG) by Mandard. The primary endpoint of this study was the difference in pathological response to nCRT between TSR-high and TSR-low groups. RESULTS: We found that 26.2% of patients with major response was classified as TSR-high, while 73.8% of patients were classified as TSR-low. A high TSR in pre-treatment biopsies was associated with a lower chance of major-response to nCRT (OR = 0.37, 95%CI; 0.19-0.73), p = 0.004), independent of tumour stage and time between nCRT and surgery. CONCLUSION: In rectal cancer, TSR in pre-treatment biopsies predicts pathologic response to nCRT, with a high TSR bringing twice the risk of poor to no response compared to low TSR. In future, assessment of TSR may fulfil a role in a therapeutic algorithm identifying patients who will or will not respond to nCRT prior to treatment initiation.

A high tumour-stroma ratio (TSR) in colon tumours and its metastatic lymph nodes predicts poor cancer-free survival and chemo resistance

PurposeDespite known high-risk features, accurate identification of patients at high risk of cancer recurrence in colon cancer remains a challenge. As tumour stroma plays an important role in tumour invasion and metastasis, the easy, low-cost and highly reproducible tumour-stroma ratio (TSR) could be a valuable prognostic marker, which is also believed to predict chemo resistance.MethodsTwo independent series of patients with colon cancer were selected. TSR was estimated by microscopic analysis of 4 µm haematoxylin and eosin (H&E) stained tissue sections of the primary tumour and the corresponding metastatic lymph nodes. Patients were categorized as TSR-low (≤ 50%) or TSR-high (> 50%). Differences in overall survival and cancer-free survival were analysed by Kaplan–Meier curves and cox-regression analyses. Analyses were conducted for TNM-stage I–II, TNM-stage III and patients with an indication for chemotherapy separately.ResultsWe found that high TSR was associated with poor cancer-free survival in TNM-stage I–II colon cancer in two independent series, independent of other known high-risk features. This association was also found in TNM-stage III tumours, with an additional prognostic value of TSR in lymph node metastasis to TSR in the primary tumour alone. In addition, high TSR was found to predict chemo resistance in patients receiving adjuvant chemotherapy after surgical resection of a TNM-stage II–III colon tumour.ConclusionIn colon cancer, the TSR of both primary tumour and lymph node metastasis adds significant prognostic value to current pathologic and clinical features used for the identification of patients at high risk of cancer recurrence, and also predicts chemo resistance.

Associations between pretreatment nutritional assessments and treatment complications in patients with stage I-III non-small cell lung cancer: A systematic review.

BACKGROUND: Patients with stage I-III non-small cell lung cancer (NSCLC) are often nutritionally depleted and therefore at high-risk for treatment complications. Identifying these patients before the start of treatment is important to initiate preventive interventions for better treatment outcomes. This study aimed to evaluate which outcome variables of pretreatment nutritional assessments are associated with posttreatment complications in patients with stage I-III NSCLC, as well as to identify cut-off values for clinical risk stratification. METHODS: In this systematic review, PubMed, Embase, and Cinahl databases were searched for eligible studies published up to March 2021. Studies describing the association between pretreatment nutritional assessment and treatment complications in patients with NSCLC were included. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale for cohort studies. RESULTS: A total of 23 studies were included, which merely focused on surgical treatment for NSCLC. Methodological quality was poor in thirteen studies (57%). Poor outcomes of body mass index, sarcopenia, serum albumin, controlling nutritional status, prognostic nutrition index, nutrition risk score, and (geriatric) nutrition risk index were associated with a higher risk for treatment complications. Cut-off values for pretreatment nutritional assessment were reported in a limited number of studies and were inconsistent. CONCLUSION: Poor outcomes of pretreatment nutritional assessments are associated with a higher risk for posttreatment complications. Further research is needed on the ability of easy-to-use pretreatment nutritional assessments to accurately identify patients who are at high risk for treatment complications, as high-risk patients may benefit from pretreatment interventions to improve their nutritional status.

A high tumour-stroma ratio (TSR) in colon tumours and its metastatic lymph nodes predicts poor cancer-free survival and chemo resistance.

PURPOSE: Despite known high-risk features, accurate identification of patients at high risk of cancer recurrence in colon cancer remains a challenge. As tumour stroma plays an important role in tumour invasion and metastasis, the easy, low-cost and highly reproducible tumour-stroma ratio (TSR) could be a valuable prognostic marker, which is also believed to predict chemo resistance. METHODS: Two independent series of patients with colon cancer were selected. TSR was estimated by microscopic analysis of 4 µm haematoxylin and eosin (H&E) stained tissue sections of the primary tumour and the corresponding metastatic lymph nodes. Patients were categorized as TSR-low (≤ 50%) or TSR-high (> 50%). Differences in overall survival and cancer-free survival were analysed by Kaplan-Meier curves and cox-regression analyses. Analyses were conducted for TNM-stage I-II, TNM-stage III and patients with an indication for chemotherapy separately. RESULTS: We found that high TSR was associated with poor cancer-free survival in TNM-stage I-II colon cancer in two independent series, independent of other known high-risk features. This association was also found in TNM-stage III tumours, with an additional prognostic value of TSR in lymph node metastasis to TSR in the primary tumour alone. In addition, high TSR was found to predict chemo resistance in patients receiving adjuvant chemotherapy after surgical resection of a TNM-stage II-III colon tumour. CONCLUSION: In colon cancer, the TSR of both primary tumour and lymph node metastasis adds significant prognostic value to current pathologic and clinical features used for the identification of patients at high risk of cancer recurrence, and also predicts chemo resistance.

Associations between the Geriatric-8 and 4-meter gait speed test and subsequent delivery of adjuvant chemotherapy in older patients with colon cancer.

OBJECTIVES: Feasible screening methods are important to identify older patients who might benefit from adjuvant chemotherapy. The aim of this study was to investigate the associations between the outcomes of screening for frailty with the Geriatric-8 questionnaire (G8) and the 4-meter gait speed test (4MGST) and subsequent delivery of adjuvant chemotherapy and treatment tolerance in older patients with colon cancer. MATERIAL AND METHODS: This retrospective multicentre study included all patients aged ≥70 with primary colon carcinoma who underwent elective surgery between May 2016 and December 2018 and for whom adjuvant chemotherapy was indicated. Data were analysed using multivariate regression models. RESULTS: 97 (73.5%) of 132 eligible patients were screened by the G8 and 85 (64.4%) by the 4MGST. In univariate analyses, patients who scored indicative for frailty on both the G8 (≤14) and the 4MGST (>4 s) significantly more often did not proceed with adjuvant chemotherapy than patients who scored fit on both instruments (OR = 5.10, p = 0.01). After adjustment for gender, stage, and postoperative complications, the OR decreased to 4.22 (p = 0.04). Tolerance of treatment was very high (93%) and did not differ between screening groups. CONCLUSION: Although patients who scored indicative for frailty on both the G8 and the 4MGST significantly more often did not proceed with adjuvant chemotherapy, it is still unknown whether the G8 and the 4MGST are reliable tools for identifying patients who are at high risk for severe chemotoxicity. Nonetheless, this study shows that current selection for adjuvant chemotherapy among older patients with colon cancer is safe with low rates of severe chemotoxicity.

Associations between pretreatment physical performance tests and treatment complications in patients with non-small cell lung cancer: A systematic review.

This systematic review evaluated which outcome variables and cut-off values of pretreatment exercise tests are associated with treatment complications in patients with stage I-III non-small cell lung cancer (NSCLC). PRISMA and Cochrane guidelines were followed. A total of 38 studies with adult patients undergoing treatment for stage I-III NSCLC who completed pretreatment exercise tests, and of whom treatment-related complications were recorded were included. A lower oxygen uptake at peak exercise amongst several other variables on the cardiopulmonary exercise test and a lower performance on field tests, such as the incremental shuttle walk test, stair-climb test, and 6-minute walk test, were associated with a higher risk for postoperative complications and/or postoperative mortality. Cut-off values were reported in a limited number of studies and were inconsistent. Due to the variety in outcomes, further research is needed to evaluate which outcomes and cut-off values of physical exercise tests are most clinically relevant.

Preoperative handgrip strength is not associated with complications and health-related quality of life after surgery for colorectal cancer.

Colorectal cancer (CRC) treatment is associated with a high morbidity which may result in a reduced health-related quality of life (HRQoL). The pre-operative measurement of handgrip strength (HGS) might be a tool to predict the patient's outcome after CRC surgery. The aim of this study was to evaluate the association of pre-operative HGS with the occurrence of postoperative complications and postoperative HRQoL. Stage I to III CRC patients ≥ 18 years were included at diagnosis. Demographic and clinical data as well as HGS were collected before start of treatment. HGS was classified as weak if it was below the gender-specific 25th percentile of our study population; otherwise HGS was classified as normal. The occurrence of postoperative complications within 30 days after surgery was collected from medical records. Cancer-specific HRQoL was measured 6 weeks after treatment using the EORTC QLQ-C30 and the EORTC QLQ-CR29 questionnaire. Of 295 patients who underwent surgical treatment for CRC, 67 (23%) patients had a weak HGS while 228 (77%) patients had normal HGS. 118 patients (40%) developed a postoperative complication. Complications occurred in 37% of patients with a weak HGS and in 41% of patients with a normal HGS (p = 0.47). After adjustment for age, sex, ASA, BMI and TNM, no significant associations between pre-operative HGS and the occurrence of postoperative complications and between HGS and HRQoL were found. We conclude that a single pre-operative HGS measurement was not associated with the occurrence of postoperative complications or post-treatment HRQoL in stage I-III CRC patients.

Longitudinal associations of light-intensity physical activity with quality of life, functioning and fatigue after colorectal cancer.

PURPOSE: Evidence from cross-sectional studies suggests that higher levels of light-intensity physical activity (LPA) are associated with better health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. However, these associations have not been investigated in longitudinal studies that provide the opportunity to analyse how within-individual changes in LPA affect HRQoL. We investigated longitudinal associations of LPA with HRQoL outcomes in CRC survivors, from 6 weeks to 2 years post-treatment. METHODS: Data were used of a prospective cohort study among 325 stage I-III CRC survivors (67% men, mean age: 67 years), recruited between 2012 and 2016. Validated questionnaires were used to assess hours/week of LPA (SQUASH) and HRQoL outcomes (EORTC QLQ-C30, Checklist Individual Strength) at 6 weeks, and 6, 12 and 24 months post-treatment. We applied linear mixed regression to analyse longitudinal confounder-adjusted associations of LPA with HRQoL. RESULTS: We observed statistically significant longitudinal associations between more LPA and better global quality of life and physical, role and social functioning, and less fatigue over time. Intra-individual analysis showed that within-person increases in LPA (per 8 h/week) were related to improved HRQoL, including better global quality of life (ß = 1.67, 95% CI 0.71; 2.63; total range scale: 0-100) and less fatigue (ß = - 1.22, 95% CI - 2.37; - 0.07; scale: 20-140). Stratified analyses indicated stronger associations among participants below the median of moderate-to-vigorous physical activity (MVPA) at diagnosis. CONCLUSION: Higher levels of LPA were longitudinally associated with better HRQoL and less fatigue in CRC survivors up to two years post-treatment. Further prospective studies using accelerometer data are necessary to inform development of interventions targeting LPA.

Functional bowel complaints and quality of life after surgery for colon cancer: prevalence and predictive factors.

AIM: Low anterior resection syndrome (LARS) severely affects the quality of life (QoL) of patients after surgery for rectal cancer. There are very few studies that have investigated LARS-like symptoms and their effect on QoL after colon cancer surgery. The aim of this study was to investigate the prevalence of functional abdominal complaints and related QoL after colon cancer surgery compared with patients with similar complaints after rectal cancer surgery. METHOD: All patients who underwent colorectal cancer resections between January 2008 and December 2015, and who were free of colostomy for at least 1 year, were eligible (n = 2136). Bowel function was assessed by the LARS score, QoL by the EORTC QLQ-C30 and QLQ-CR29 questionnaires. QoL was compared between the LARS score categories and tumour height categories. RESULTS: A total of 1495 patients (70.0%) were included in the analyses, of whom 1145 had a colonic and 350 a rectal tumour. Symptoms of LARS were observed in 55% after rectal cancer resection compared with 21% after colon cancer resection. Female gender (OR 1.88, CI 1.392-2.528) and a previous diverting stoma (OR 1.84, CI 1.14-2.97) were independently associated with a higher prevalence of LARS after colon cancer surgery. Patients with LARS after colon cancer surgery performed significantly worse in most QoL domains. CONCLUSION: The results of this study highlight the presence of LARS-like symptoms after surgery for colonic cancer. Patients suffering from major LARS-like symptoms after colon resection reported the same debilitating effect on their QoL as patients with major LARS after rectal resection. This should be addressed by colorectal cancer specialists in order to adequately inform patients.

The low anterior resection syndrome in a reference population: prevalence and predictive factors in the Netherlands.

AIM: The low anterior resection syndrome (LARS) severely affects quality of life (QoL) after colorectal cancer surgery. There are no data about these complaints and the association with QoL in a reference population. The aim of this study was to assess LARS and the association with QoL in a reference population. METHODS: Six hundred patients who visited the outpatient clinic because of general or trauma surgical indications were asked to participate in this study. They received an invitation letter containing three validated questionnaires to assess LARS (assessed with the LARS score) and both general [European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30] and colorectal-specific (EORTC QLQ-CR29) QoL. RESULTS: Five hundred and one respondents could be included for the analyses. The median age at inclusion was 68 years and 47.3% were men. Major LARS was observed in 15% of patients (11.4% in men and 18.9% in women, P = 0.021). Women reported more urgency (P = 0.070) and incontinence for both flatus (P < 0.001) and stool (P = 0.063) compared to men. In univariate analyses, women reported major LARS significantly more often than men (OR 1.82; 95% CI 1.10-3.01). Patients with major LARS scored significantly worse in most QoL domains compared to patients with no/minor LARS. CONCLUSION: This is the first study demonstrating major LARS and the association with QoL in a reference population of patients without colorectal cancer. Our data can assist in the interpretation of LARS in past and future research about abdominal complaints after colorectal cancer surgery.

Bowel dysfunction after sigmoid resection underestimated: Multicentre study on quality of life after surgery for carcinoma of the rectum and sigmoid.

AIM: The Low Anterior Resection Syndrome (LARS) severely affects quality of life (QoL) after rectal cancer surgery. There are no data about functional complaints after sigmoid cancer surgery. We investigated LARS and QoL in patients with a resection for sigmoid cancer versus patients who had surgery for rectal cancer. METHODS: 506 patients after resection for rectal or sigmoid cancer who were at least one year colostomy-free were included between January 2008 and December 2013. Bowel function was assessed by the LARS-Score. QoL was assessed by the EORTC QLQ-C30 and -CR29 questionnaires. QoL was compared between the LARS score categories and tumour height categories. RESULTS: 412 respondents (81.5%) could be included for the analyses. The median interval since treatment was 5 years, and the median age at the follow-up point was 72 years. Major LARS increased significantly with decreasing tumour height from one fifth in sigmoid carcinoma to 90% in low rectum carcinoma. Female gender (OR = 2.162; 95% CI: 1.349-3.467), postoperative temporary diverting stoma (OR = 3.457; 95% CI: 2.019-5.919) and tumours located in the middle (OR = 3.193; 95% CI: 1.696-6.010) or lower rectum (OR = 8.247; 95% CI: 1.672-40.678) were independently associated with the development of major LARS. Patients with major LARS fared significantly worse in most QOL domains. CONCLUSIONS: For the first time, we found that functional abdominal complaints after sigmoid surgery are a major problem, with a negative effect on QoL, even 5 years after treatment. Patients need to be adequately informed about these long-term complaints.

Guideline versus non-guideline based management of rectal cancer in octogenarians.

PURPOSE: The number of octogenarians with rectal adenocarcinoma is growing. Current guidelines seem difficult to apply on octogenarians which may result in non-adherence. The aim of this retrospective cohort study is to give insight in occurrence of treatment-related complications, hospitalisations and survival among octogenarians treated according to guidelines versus octogenarians treated otherwise. METHODS: 108 octogenarians with rectal adenocarcinoma were identified by screening of medical records. 22 patients were excluded for treatment process analysis because of stage IV disease or unknown stage. Baseline characteristics, diagnostic process, received treatment, motivation for deviation from guidelines, complications, hospitalisations and date of death were documented. Patients were divided in two groups depending on adherence to treatment guidelines. Differences in baseline characteristics, treatment-related complications and survival between both groups were evaluated. RESULTS: Diagnosis and treatment according to guidelines occurred in 95 and 54% of the patients, respectively. When documented, patient's preference and comorbidities were major reasons to deviate from guidelines. 66% of patients who were treated according to guidelines experienced complications versus 34% of those treated otherwise (p = 0.02). After adjustment for differences in age and polypharmacy, this association was not significant. Patients treated according to the guideline had better survival 18 months after diagnosis (80 versus 56%, p = 0.02). CONCLUSIONS: Treating octogenarians with rectal cancer according to guidelines seem to lead to better overall survival, but may lead to a high risk of complications. This may jeopardise quality of life. More and prospective studies in octogenarians with rectal cancer are needed to customize guidelines for these patients.

Preoperative segmental localization of colorectal carcinoma: CT colonography vs. optical colonoscopy.

BACKGROUND: Adequate preoperative segmental localization of colorectal cancer is important to indicate the right surgical treatment. Preoperative localization has become more important in the era of minimally invasive surgery. The aim of this study was to compare optical colonoscopy (OC) and CT colonography (CTC) with respect to the error rates in the segmental localization of colorectal carcinoma. METHODS: A total of 420 patients with histopathologically proven colorectal carcinoma underwent CTC between December 2006 and February 2017. 284 Of these patients underwent surgical resection and had their carcinomas located on CTC report as well as OC report and surgical report. The segmental localization error rates of OC and CTC were compared using surgery as golden standard. McNemar's test was used to evaluate the differences in error rate. RESULTS: 284 Patients with a total of 296 colorectal carcinomas were evaluated. The segmental localization error rate of CTC (39/296, 13.2%) was found to be lower than the segmental localization error rate of OC (64/296, 21.6%) (p < 0.001). Per segment analysis showed that OC had a significantly higher error rate for carcinomas located in the descending colon (60.6% vs. 21.2% [p < 0.001] and cecum(60.0% vs. 23.3% [p = 0.001]). In 9.2% of the patients (26/284), localization based on CTC would lead to a change in surgical plan. CONCLUSION: CTC has a lower localization error rate than OC, which is most relevant for tumors located in the descending colon. If there is a doubtful localization on OC, particularly in the left-sided colon, an additional CTC should be performed to choose the best surgical treatment.

Detection of potentially relevant extracolonic and colorectal findings at CT colonography in a low-risk symptomatic patient population.

PURPOSE: CT colonography (CTC) is a widely accepted examination tool for detection of colorectal lesions but evidence of the proportions of relevant extracolonic findings (ECF) in a large symptomatic but still relatively low-risk cohort is lacking, as well as their relationship to symptoms, age, and sex. METHODS: All patients (n = 3208) with colorectal symptoms, imaged between January 2007 and September 2016 with first-time CTC, were retrospectively selected. The majority (96.7%) was examined with low-dose unenhanced protocol. The most relevant ECF and colorectal lesions (≥6 mm) were prospectively assessed according to C-RADS classifications. Follow-up was elaborated based on the electronic record review. Chi-square test was utilized for evaluating the associations between relevant findings and symptoms, age, and sex. RESULTS: A total of 270 (8.4%) patients were classified as C-RADS E3, 63 (2.0%) patients as C-RADS E4, and 437 (13.6%) patients were assessed with colorectal lesions (C-RADS C2-4). At follow-up, two thirds of ECF turned out to be a malignancy or relevant disease that required further medical attention. The proportion of ECF was not related to specific colorectal symptoms. Patients aged ≥65 years and men had significantly higher proportions of ECF than younger patients (C-RADS E3 p = 0.005; C-RADS E4 p < 0.001) and women (C-RADS E3 p = 0.013; C-RADS E4 p = 0.009), respectively. CONCLUSION: Proportions of relevant ECF and colorectal findings are relatively low in symptomatic low-risk patients. By use of CTC as a singular examination, especially in elderly patients, most colonoscopies can be avoided with the benefit of diagnosing relevant ECF without introducing substantial over-diagnosis.

Impact of detection bias on the risk of gastrointestinal cancer and its subsites in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias. METHODS: A matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998-2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation. RESULTS: An increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3-1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2-1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1-7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5-11.8) and distal colon cancer (HR 1.5, 95% CI 1.1-2.1) were found, which remained statistically significantly increased in the lagged analysis. CONCLUSIONS: T2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised.

Recurrence-free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy.

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence-free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non-)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non-academic hospitals were included. RFS and OS were analyzed with Kaplan-Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five-year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p = 0.91), adjusted HR = 0.99 (95%CI 0.68-1.44); OS: 66% vs. 66% (p = 0.76), adjusted HR = 0.93 (95%CI 0.64-1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three-year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR = 1.42 (95%CI 0.85-2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI 0.70-1.97)). Three-year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11-3.84); OS: 65% vs. 80% (p = 0.01), adjusted HR = 2.00 (95%CI 1.12-3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.

Epidemiology, management and survival outcomes of primary cutaneous melanoma: a ten-year overview.

BACKGROUND: Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. METHODS: Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated. RESULTS: The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p < .01) and a significantly higher Breslow thickness than women (1.2 mm vs. 0.9 mm, p < .01). 14.6% (40/273) underwent sentinel lymph node biopsy (SLNB); 10/40 (25%) showed nodal metastasis, 50 patients (7.3%) developed distant metastases (M: 10.6%, F: 5%, p < .01). One-, 5- and 10- year disease specific survival rates were 96%, 86% and 84%, respectively. Median survival for stage 4 MM was 3 months. Extensive surgery was uncommon (n = 3). CONCLUSIONS: Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.

Intensity of adjuvant chemotherapy regimens and grade III-V toxicities among elderly stage III colon cancer patients.

PURPOSE: The aim of this study was to provide insight in the use, intensity and toxicity of therapy with capecitabine and oxaliplatin (CAPOX) and capecitabine monotherapy (CapMono) among elderly stage III colon cancer patients treated in everyday clinical practice. METHODS: Data from the Netherlands Cancer Registry were used. All stage III colon cancer patients aged ≥70 years diagnosed in the southeastern part between 2005 and 2012 and treated with CAPOX or CapMono were included. Differences in completion of all planned cycles, cumulative dosages and toxicity between both regimens were evaluated. RESULTS: One hundred ninety-three patients received CAPOX and 164 patients received CapMono; 33% (n = 63) of the patients receiving CAPOX completed all planned cycles of both agents, whereas 55% (n = 90) of the patients receiving CapMono completed all planned cycles (P < 0.0001). The median cumulative dosage capecitabine was lower for patients treated with CAPOX (163,744 mg/m(2), interquartile range [IQR] 83,397-202,858 mg/m(2)) than for patients treated with CapMono (189,195 mg/m(2), IQR 111,667-228,125 mg/m(2), P = 0.0003); 54% (n = 105) of the patients treated with CAPOX developed grade III-V toxicity, whereas 38% (n = 63) of the patients treated with CapMono developed grade III-V toxicity (P = 0.0026). After adjustment for patient and tumour characteristics, CapMono was associated with a lower odds of developing grade III-V toxicity than CAPOX (odds ratio 0.54, 95% confidence interval 0.33-0.89). For patients treated with CAPOX, the most common toxicities were gastrointestinal (29%), haematological (14%), neurological (11%) and other toxicity (13%). For patients treated with CapMono, dermatological (17%), gastrointestinal (13%) and other toxicity (11%) were the most common. CONCLUSION: CAPOX is associated with significantly more grade III-V toxicities than CapMono, which had a pronounced impact on the cumulative dosage received and completion of all planned cycles. In this light, CapMono seems preferable over CAPOX.