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The aim of this study was to longitudinally investigate dietary and lifestyle inflammation scores and their interaction in relation to risk of colorectal cancer (CRC) recurrence and all-cause mortality. Data of two prospective cohort studies among CRC survivors was used. Information about diet and/or lifestyle was available for 2739 individuals for at least one of the following time points: at diagnosis, six months after diagnosis and two years after diagnosis. The dietary and lifestyle inflammation scores (DIS and LIS) were used to evaluate the inflammatory potential of diet and lifestyle. Joint modelling, combining mixed models and Cox proportional hazards regression, were used to assess associations between DIS and LIS over time and CRC recurrence and all-cause mortality. Interactions between DIS and LIS were assessed using time-dependent Cox proportional hazard regression. The median follow-up time was 4.8 (IQR 2.9–6.9) years for recurrence and 5.7 (IQR 3.5–8.5) years for all-cause mortality, with 363 and 453 events, respectively. A higher DIS as well as LIS was associated with a higher risk of all-cause mortality (HR DIScontinuous 1.09 95%CI 1.02; 1.15; HR LIScontinuous 1.24 95%CI 1.05; 1.46). Individuals who were in the upper tertile of both DIS and LIS had the highest all-cause mortality risk (HR 1.62 95%CI 1.16; 2.28), compared to the individuals in the lowest tertile of both DIS and LIS. No consistent associations with recurrence were observed. A more pro-inflammatory diet and lifestyle was associated with a higher risk of all-cause mortality, but not recurrence, in CRC survivors. [ABSTRACT FROM AUTHOR]

Patients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices. Patients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured. Before treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression). These data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery. [ABSTRACT FROM AUTHOR]

With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23–60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively. Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) follow-up has a major impact on outpatient services. The aim was to examine patient acceptability and costs of a new remote follow-up regimen for patients with CRC. All patients with stage I-III CRC and having completed at least one-year of follow-up at Radboud University Medical Center located in Nijmegen, The Netherlands, were considered for remote follow-up. Enrolled patients received the EORTC-C30 (Quality of Life, QoL), Cancer Worry Scale (Fear of Cancer Recurrence, FCR), (e)Health literacy and patient satisfaction questionnaires. Follow-up use and costs were evaluated. A total of 118 patients with stage I-III CRC have been followed according to the new remote follow-up regimen. Median length of follow-up at start of remote follow-up was 34 months (interquartile range of 24–41) and all patients were sufficiently health literate. Overall satisfaction towards remote follow-up at 6-and 12-months was rated 7.8 and 7.5 out of 10. Satisfaction with the online self-management information was rated 8 out of 10. Over a one-year period, QoL remained high and patients experienced low FCR. More than 70% of the patients self-organized their care, while the others sought contact by telephone, MyChart or hospital visits. Remote follow-up for the total cohort led to €22,408 cost-savings over one-year compared to standard hospital follow-up. Implementation of remote follow-up for patients with stage I-III CRC is feasible, comes with high patient satisfaction and considerable cost-savings. Short-term results did not show differences in QoL or FCR during the course of remote follow-up. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes for selected patients with colorectal peritoneal metastases (PM), but recurrence rates are high. The aim of this study was to develop a tool to predict recurrence in patients with colorectal PM that undergo CRS-HIPEC. For this retrospective cohort study, data of patients that underwent CRS-HIPEC for colorectal PM from four Dutch HIPEC centers were used. Exclusion criteria were perioperative systemic therapy and peritoneal cancer index (PCI) ≥20. Nine previously identified factors were considered as predictors: gender, age, primary tumor characteristics (location, nodal stage, differentiation, and mutation status), synchronous liver metastases, preoperative Carcino-Embryonal Antigen (CEA), and peritoneal cancer index (PCI). The prediction model was developed using multivariable Cox regression and validated internally using bootstrapping. The performance of the model was evaluated by discrimination and calibration. In total, 408 patients were included. During the follow-up, recurrence of disease occurred in 318 patients (78%). Significant predictors of recurrence were PCI (HR 1.075, 95% CI 1.044–1.108) and primary tumor location (left sided HR 0.719, 95% CI 0.550–0.939). The prediction model for recurrence showed fair discrimination with a C-index of 0.64 (95% CI 0.62, 0.66) after internal validation. The model was well-calibrated with good agreement between the predicted and observed probabilities. We developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC. [ABSTRACT FROM AUTHOR]

The inflammatory potential of the diet has been linked to colorectal cancer (CRC) development and mortality. However, it is unknown whether it is also associated with CRC recurrence. Therefore, the aim of this study was to investigate the associations between the inflammatory potential of the diet and plasma inflammation markers as well as recurrence and all-cause mortality in CRC patients. Data of the Colorectal cancer, Observational, LONgitudinal (COLON) study, a prospective cohort study, was used. Dietary intake, assessed using a semi-quantitative food frequency questionnaire, was available for 1478 patients at diagnosis and for 1334 patients six months after diagnosis. Dietary intake data were used to calculate the adapted dietary inflammatory index (ADII). Data about cancer recurrence and all-cause mortality, were assessed through linkage with the Netherlands Cancer Registry and the Municipal Personal Records Database, respectively. The association between the ADII (continuous) and inflammation markers (Interleukin (IL)6, IL8, IL10, Tumor Necrosis Factor (TNF)α, high sensitivity C-reactive protein (hsCRP) and a summary inflammatory z-score), measured with a multiplex assay using electrochemiluminiscence detection, was assessed using quantile regression analyses. Restricted cubic splines (RCS) analyses and multivariable Cox proportional hazard models were used to explore the relationship between the ADII and CRC outcomes. During a median follow-up time of 3.2 years (Interquartile range (IQR) 2.0–4.1) for recurrence and 4.8 years (IQR 3.5–5.9) for all-cause mortality, 228 recurrences and 279 deaths occurred. A more pro-inflammatory diet at diagnosis as well as six months after diagnosis was associated with higher levels of TNFα, hsCRP and the summary inflammatory z-score. Results of RCS showed no relationship between the ADII and CRC outcomes at both time points. Also results of the Cox proportional hazard models showed no associations between the ADII at both time points and recurrence (HR (95%CI) 0.98 (0.94–1.04) & 0.96 (0.91–1.02) or all-cause mortality (HR (95%CI) 1.03 (0.98–1.07) & 1.00 (0.95–1.05)). Our study did not show an association between the ADII and recurrence and all-cause mortality in CRC patients. Further research should also take into account molecular tumor subtypes, as the effect of the inflammatory potential of the diet on cancer recurrence and mortality is more likely to be present in tumors with an inflammatory signature. The colon study: NCT03191110; clinical trials.gov. [ABSTRACT FROM AUTHOR]

Regional recurrence (RR), also known as lymph node recurrence, is an endpoint in several trials concerning reducing axillary treatment in cT1-2N0 breast cancer patients. The risk of RR may decrease with each subsequent event-free year, affecting the yield and consequently usefulness of long (er) follow-up. The aim of this study is to determine the risk of RR as a first event within five years after diagnosis in subtypes of breast cancer, conditional to being event-free for one, two, three and four years. From the Netherlands Cancer Registry, cT1-2N0 breast cancer patients diagnosed from 2005 to 2008 were analyzed. Subgroup analysis was performed for pT1-2N+(sn) patients. RR risk was calculated with Kaplan-Meier analysis. Conditional RR (assuming x event-free years) was determined by selecting patients without an event at x years, and calculating the remaining risk for RR within five years after diagnosis. A total of 18,009 cT1-2N0 (all pN stages) breast cancer patients were included. RR occurred in 1.3% of cT1-2N0 and 1.5% of pT1-2N+(sn) patients. The risk of RR varied between subtypes; it was highest for triple negative tumors and lowest for ER + PR + Her2-and ER + Her2+ tumors. After event-free years, the risk of RR decreased subsequently in both groups and in all subtypes. After two event-free years, the risk of RR was 0.8%. The absolute yield of follow-up to detect RR beyond two years is low; for every 125 event-free patients, one RR can be expected until five years. This suggests that follow-up longer than two years is of limited value for detecting RR in both clinical and research setting. [ABSTRACT FROM AUTHOR]

Evidence on the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leak (AL) rate after colorectal surgery is conflicting. Effects of NSAIDs might depend on the underlying disease. This meta-analysis aimed to review the effect of NSAIDs on AL rate in a homogeneous colorectal cancer patient population. A systematic literature search using MEDLINE and EMBASE database was performed for studies with AL as primary outcome comparing NSAID use in the early postoperative phase with no NSAID administration in colorectal cancer patients undergoing surgical resection. Nine studies including 10,868 patients met the inclusion criteria. The majority, 7689 patients (70.7%) underwent low anterior resection and 3050 patients (28.1%) underwent colonic resection. The pooled incidence of AL was 8.6% (95%CI 7.0–10.0). Overall AL rate after colorectal cancer surgery was not increased in patients using NSAIDs for postoperative analgesia compared to non-users (p = 0.34, RR 1.23; 95%CI 0.81–1.86). This effect remained non-significant after stratification for low anterior resections (p = 0.07). Stratification for colonic resections could not be performed because AL results for this subgroup were not reported separately. Neither non-selective NSAID use nor COX-2 selective NSAID use caused an increased AL rate (p = 0.19, p = 0.26). The results were robust throughout sensitivity analyses. Use of NSAIDs in cohorts with patients undergoing surgical resection for colorectal cancer does not increase overall AL rate. Since results were robust throughout several subgroup and sensitivity analyses, prescription of NSAIDs after colorectal cancer surgery seems safe. [ABSTRACT FROM AUTHOR]

This study aimed to investigate hospital variability in postoperative mortality and anastomotic leakage (AL) after colorectal cancer surgery, as well as the association with hospital volume and teaching status. This nationwide population based study derived data from CRC patients who underwent a surgical resection with primary anastomosis from the Netherlands Cancer Registry between 2015 and 2020. Primary outcomes were 90-day mortality and AL for colon cancer (CC) patients, and AL for rectal cancer (RC) patients. Logistic regression modelling was used to evaluate the association between case-mix factors and hospital volume. Variability in outcomes between hospitals was analysed with Poisson regression. This study included 44,101 CRC patients, comprising 35,164 CC patients, and 8937 RC patients. In the CC cohort, the unadjusted rates of AL ranged from 2.6 % to 14.4 %, and the unadjusted 90-day mortality rates ranged from 0.0 % to 6.7 %. In the RC cohort, the unadjusted rates of AL ranged from 0.0 % to 28.6 %. After case-mix adjustment, two hospitals performed significantly worse than expected regarding 90-day mortality in the CC cohort, and in both CC and RC cohorts, significant outliers were observed concerning AL. Amongst CC patients, low case volume (OR 1.26 95%CI 1.08–1.46) was significantly associated with AL. Statistically significant variations in hospital performance were observed among Dutch hospitals after CRC surgery, but this effect could not be entirely attributed to hospitals' teaching status. Nevertheless, concentrating care has the potential to improve outcomes by enhancing individual surgical performance and optimizing care pathways. [ABSTRACT FROM AUTHOR]

Abstract Introduction Patients with pT4 colon cancer are at risk of developing intra-abdominal recurrence. Infectious complications have shown to negatively influence disease free survival (DFS) and overall survival (OS) in stage I-III colon cancer. The aim of this study was to determine whether surgical site infections (SSIs) also increase the risk of intra-abdominal recurrence in pT4 colon cancer patients. Methods All consecutive patients with pT4N0-2M0 colon cancer from four centres between January 2000 and December 2014 were included. Patients were categorized into 2 groups; with and without a postoperative (<30 days) SSIs. SSIs included both deep incisional as well as organ/space SSIs. The primary outcome was intra-abdominal recurrence (including local/incisional recurrence, peritoneal metastases) and was assessed using Kaplan-Meier and Cox regression analyses. Secondary outcome measures were DFS and OS. Results Out of 420 patients, 62 (15%) developed a SSI. The 5-year intra-abdominal recurrence rates were 44% and 27% for patients with and without a SSI, respectively (p = 0.011). After multivariate analysis, SSI was independently associated with intra-abdominal recurrence (HR 1.807 (1.091–2.992)), worse DFS (HR 1.788 (1.226–2.607)), and worse OS (HR 1.837 (1.135–2.973)). Other independent risk factors for intra-abdominal recurrence were a R1 resection (HR 2.616 (1.264–5.415)) and N2-stage (HR 2.096 (1.318–3.332)). Conclusion SSIs after resection of a pT4N0-2M0 colon cancer are associated with an increased risk of intra-abdominal recurrence and worse survival. This finding supports the hypothesis that infection-based immunologic pathways play a role in colon cancer cell dissemination and outgrowth. [ABSTRACT FROM AUTHOR]

Background This study aims to provide insight in the quality of current daily practice in clinical lymph node staging in colorectal cancer (CRC) in the Netherlands. Methods Data of the nationwide population-based Netherlands Cancer Registry between 2003 and 2014 were used to analyze lymph node staging for cM0 CRC patients. Accuracy of clinical lymph node staging was calculated for the period 2011–2014. Analyses were performed for patients without preoperative treatment or treated with short-course radiotherapy (SCRT) followed by resection. Results 100,211 patients were included for analysis. The proportion clinically positive lymph nodes increased significantly between 2003 and 2014 (6%–22% for colon cancer; 7%–53% for rectal cancer). The proportion histological positive lymph nodes remained stable (±35% colon, ±33% rectum). Data from 2011 to 2014 yielded a sensitivity, specificity, positive and negative predictive value of 41%, 84%, 59% and 71% for colon cancer, respectively (n = 21,629). This was 38%, 87%, 56%, 76% for rectal cancer without SCRT, (n = 2178) and 56%, 67%, 47% and 75% for rectal cancer with SCRT (n = 3401), respectively. Conclusion Accuracy of clinical lymph node staging in colorectal cancer patients is about as accurate as flipping a coin. This may lead to overtreatment of rectal cancer patients. Acceptable specificity and NPV limit the risk of undertreatment. [ABSTRACT FROM AUTHOR]

Treatment of rectal cancer patients has been subjected to change over the past thirty years. Total mesorectal excision is considered the cornerstone of rectal cancer treatment, but is also associated with significant morbidity resulting in an impaired quality of life. The addition of neoadjuvant chemoradiotherapy to surgery has shown to improve survival and local control and may lead to a partial or even complete response (CR). This raises questions regarding the necessity for subsequent radical surgery. After careful patient selection local excision and wait-and-see approaches are explored, aiming to improve quality of life without compromising oncological outcome. A multimodality diagnostic approach for optimal staging is crucial in determining the appropriate neoadjuvant treatment regimen. Adequate endoscopic restaging of rectal tumours after multimodality treatment will aid in selecting patients who are eligible for an organ preserving approach. The role and accuracy of imaging in the detection of the primary tumour, residual rectal cancer or local recurrence seems vital. Alternative neoadjuvant regimens are currently explored to increase the rate of clinical CRs, which may support organ preserving approaches. This review aims to generate insight into the advances in diagnostics and treatment modalities in all stages of rectal cancer and will highlight future studies that may support further implementation of organ preservation treatment in rectal cancer. [ABSTRACT FROM AUTHOR]

Introduction There is an ongoing controversy surrounding portal vein embolization (PVE) regarding the short-term safety of PVE and long-term oncological benefit. This study aims to compare survival outcomes of patients subjected to major liver resection for colorectal liver metastases (CRLM) with or without PVE. Methods All consecutive patients who underwent major liver resection for CRLM in four high volume liver centres between January 2000 and December 2015 were included. Major liver resection was defined as resection of at least three Couinaud liver segments. To reduce selection bias, propensity score matching was performed for PVE and non-PVE patients with overall and disease-free survival as primary endpoints. For matching, all patients who underwent PVE followed by a major liver resection were selected. Patients were matched to patients who had undergone major liver resection without PVE. Results Of 745 patients undergoing major liver resection for CRLM, 53 patients (7%) underwent PVE before liver resection. In the overall cohorts, PVE patients had inferior DFS and a trend towards inferior OS. A total of 46 PVE patients were matched to 46 non-PVE patients to create comparable cohorts and between these two matched cohorts no differences in DFS (3-year DFS 16% vs 9%, p = 0.776) or OS (5-year OS 14% vs 14%, p = 0.866) were found. Conclusions This retrospective, matched analysis does not suggest a negative impact of PVE on long-term outcomes after liver resection in patients with CRLM. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To retrospectively analyze the outcome of patients with anaplastic thyroid carcinoma (ATC) treated in the Erasmus MC. Material and methods: Seventy-five ATC-patients were treated between 1972 and 2003. Mean age was 68 years. Tumor stage was IVA in 9%, IVB in 51%, and IVC in 40%. Thirty-six patients underwent up-front surgery, with 53% resulting in R0/R1 resection. Before 1988 adjuvant treatment consisted of conventional radiotherapy (RT) and/or chemotherapy (CT). As of 1988, 30 eligible patients were enrolled in a newly designed protocol. This consists of locoregional RT in 46 fractions of 1.1Gy, given twice daily, followed by prophylactic irradiation of the lungs (PLI) in 5 daily fractions of 1.5Gy. During radiation, low-dose Doxorubicine (15mg/m2) is administered weekly and is followed by adjuvant Doxorubicine (50mg/m2) 3-weekly up to a cumulative dose of 550mg/m2. Twenty-five ineligible patients were treated conventionally. Results: Overall median survival was 3months, 1-year OS 9%. Locoregional control was significantly higher in patients who had undergone R0/R1 resection or chemoradiation, with best results for patients who underwent both (complete remission in 89%). However, the survival benefit of patients who reached CR remained borderline (median OS 7months, 1-year OS 32%). Three patients survived for more than 5years; all had undergone R0/R1 surgical resection and chemoradiation. Acute toxicity in the protocol group was significantly higher than in the nonprotocol group, with 46% versus 11% grade 3 pharyngeal and/or esophageal toxicity. Conclusion: Despite the ultimately dismal prognosis of ATC-patients, multimodality treatment significantly improved local control and improved the median survival. [Copyright &y& Elsevier]

Abstract: The sentinel node (SN) procedure in melanoma patients is important for prognostic information, but has no impact on survival. Micrometastases are identified in approximately 20% of the SNs. When a Completion Lymph Node Dissection (CLND) is performed for positive SN, additional non-SN lymph node involvement is also approximately 20%. Several classification criteria have been proposed to identify patients with SNs without a risk for additional nodes or a good prognosis. Micro anatomic analyses of metastatic SNs suggest that patients with sub-micrometastases (<0.1mm) in the SN may be judged as SN negative. Patients with this limited tumor burden in their SN have an excellent prognosis and are highly unlikely to benefit from CLND. New techniques such as ultrasound of the lymph nodal basin can be promising as an alternative for SN biopsy. [Copyright &y& Elsevier]

Abstract: Objective: Analyse the outcome of pelvic exenteration for gynaecological malignancies in a tertiary referral center. Post-operative in-hospital morbidity, long-term morbidity, disease free and overall survival rates were studied. Study design: Between 1991 and 2004, 42 patients underwent an anterior, total or posterior exenteration for gynaecological malignancies. Follow-up was obtained from patient files; disease free and overall survival were calculated and prognostic factors were studied. Results: A pelvic exenteration was performed in 14 patients for primary and 28 patients for recurrent gynaecological cancers. In-hospital complications occurred in 19 patients (45%) of whom seven patients needed a reoperation (17%). Late complications occurred in 31 patients (75%); 21 reinterventions were performed (50%). Five-year disease free and overall survival was, respectively, 48 and 52%. Age, type of surgery, histology, localisation of the tumour, lateral wall involvement, completeness of resection and primary versus recurrent cancer were not identified as prognostic factors for recurrence or survival. Conclusion: Long-term survival is possible in about 50% of patients after pelvic exenteration for gynaecological cancers, but is associated with significant post-operative morbidity. [Copyright &y& Elsevier]

Background Although synchronous and metachronous metastases are considered as separate entities of metastatic colorectal cancer (mCRC) with different outcomes, its proportion is reported infrequently. We compared inclusion rates and survival of synchronous versus metachronous mCRC in different types of studies investigating initial systemic therapy or surgical treatment of mCRC. Methods We searched PubMed and EMBASE (January 2004 – February 2016) for mCRC studies investigating first-line systemic therapy or surgical treatment of mCRC including information on synchronous versus metachronous metastases. Outcomes were the proportion of synchronous mCRC, and estimated median overall survival (OS) of the total study population. Spearman analysis (r s ) was used to study correlations between outcomes and median year of study enrolment. Results We included 46 articles, reporting data from 23 phase 3 randomised controlled trials (RCTs), twenty cohort and three population-based studies (total: 25,941 patients). Seventeen different definitions for synchronous mCRC were identified. In systemic therapy RCTs, we observed an increased proportion of synchronous mCRC during recent years (r s .77, p < .001). In these trials, estimated median OS slightly improved over time (r s .48, p = .03). No significant inclusion or survival trends were observed in included cohort and population-based studies. Conclusions In recent years, the proportion of patients with synchronous compared with metachronous mCRC enrolled in first-line systemic therapy RCTs increased. Estimated median OS of the total study population in these RCTs slightly increased over time. Many different definitions of synchronous disease were used. Uniform definitions and consistent reporting of the proportion of synchronous versus metachronous metastases could improve cross-study comparisons and interpretation of reported data in all mCRC studies. [ABSTRACT FROM AUTHOR]

Background Tumour necrosis factor-α (TNF) and melphalan based isolated limb perfusion (TM-ILP) is an attractive treatment option for advanced extremity soft tissue sarcomas (STS). This study reports on a 20-year single centre experience and discusses the evolution and changes in methodology since the introduction of TNF in ILP. Patients and methods We performed 306 TM-ILPs in 275 patients with extremity STS. All patients were candidates for amputation or mutilating surgery in order to achieve local control. Clinical response evaluation consisted of clinical examination and magnetic resonance imaging. To evaluate the importance of TNF-dose, treatment results of two periods (1991–2003 high dose (3–4 mg) TNF; 2003–2012 reduced dose (1–2 mg) TNF) were compared. Results During the study period, more femoral perfusions were done instead of iliac perfusions. Reduction of TNF dose and reduction of total ILP time did not lead to different clinical response rates (70% and 69% for periods 1 and 2 respectively) or different local recurrence rates, but was associated with less local toxicity (23% and 14% for periods 1 and 2 respectively). Hospital stay was significantly reduced during the study period. There was an improved pathological response in the high dose TNF group without consequences for clinical outcome. Conclusion TM-ILP remains a very effective treatment modality for limb threatening extremity STS. Moreover, reduction of dose and the growing experience in ILP led to less local toxicity and shorter hospital stay. [ABSTRACT FROM AUTHOR]

The epidemiology of colorectal cancer (CRC) has changed rapidly over the years. The aim of this study was to assess the trends in incidence, treatment, and relative survival (RS) of patients diagnosed with CRC in the Netherlands between 2000 and 2021. 2 75667 patients diagnosed with CRC between 2000 and 2021 were included from the Netherlands Cancer Registry. Analyses were stratified for disease extent (localised: T1-3N0M0; regional: T4N0M0/T1-4N1-2M0; distant: T1-4N0-2M1) and localisation (colon; rectum). Trends were assessed with joinpoint regression. CRC incidence increased until the mid-2010s but decreased strongly thereafter to rates comparable with the early 2000s. Amongst other trend changes, local excision rates increased for patients with localised colon (2021: 13.6 %) and rectal cancer (2021: 34.9 %). Moreover, primary tumour resection became less common in patients with distant colon (2000–2021: 60.9–12.5 %) or rectal cancer (2000–2021: 47.8–6.9 %), while local treatment of metastases rates increased. Five-year RS improved continuously for localised and regional colon (97.7 % and 72.0 % in 2017, respectively) and rectal cancer (95.2 % and 76.3 % in 2017, respectively). The rate of anti-cancer treatments decreased in distant colon (2010–2021: 80.3 % to 67.2 %; p < 0.001) and rectal cancer (2011–2021: 86.0 % to 77.0 %; p < 0.001). The improvement of five-year RS stagnated for distant colon (2010–2017: 11.2 % to 11.9 %; average percentage of change [APC]: 2.1, 95 % confidence interval [CI]: −7.6, 4.7) and rectal cancer (2009–2017: 12.7 % to 15.6 %; APC: 1.4, 95 % CI: −19.1, 5.5). Major changes in the incidence and treatment of CRC between 2000 and 2021 were identified and quantified. Five-year RS increased continuously for patients with localised and regional CRC, but stagnated for patients with distant CRC, likely caused by decreased rates of anti-cancer treatment in this group. • Clinical practice for colorectal cancer (CRC) has changed vastly in recent years. • The incidence of CRC has decreased rapidly since population screening. • Rates of anti-cancer treatment decreased for distant CRC since approximately 2010. • Relative survival increased for localised and regional CRC during the study. • For distant CRC, relative survival did not increase since approximately 2010. [ABSTRACT FROM AUTHOR]

Previous studies showed that the incidence of early-onset colorectal cancer (EO-CRC, diagnosis <50 years) is rising in Western countries. Additionally, young patients present with more advanced disease. Integrated nationwide assessment of epidemiologically and clinically relevant trends would provide more insight into this specific group of patients with CRC. We aimed to provide an analysis of trends in age- and stage-specific incidence, characteristics, treatment and relative survival of patients with EO-CRC in the Netherlands and compare these with 50- to 59-year-old patients. Data from 1989 to 2018 were retrieved from the Netherlands Cancer Registry. Non-standardised age-specific incidence rates were calculated, and trends were assessed using Joinpoint regression. Treatment and 5-year relative survival trends were provided and compared between EO-CRC and 50- to 59-year-old patients. The EO-CRC incidence annually increased with 0.7–2.1% over the last decades. CRC incidence for the 50- to 59-year-old population annually increased with 0.8–1.7% until 2006 and showed a major increase in incidence after the introduction of nationwide screening in 2014. Stage III and Stage IV CRC primarily increased across the studied age groups, while Stage I and Stage II CRC did not. Patients with EO-CRC received multimodal treatment more often than 50- to 59-year-old patients, but differences were minor. Relative survival increased over time and showed little differences between EO-CRC and 50- to 59-year-old patients. Only few epidemiological and clinical differences were found between EO-CRC and 50- to 59-year-old patients; hence, the urge for a specific approach of EO-CRC in screening and treatment guidelines might be tempered. • Early-onset colorectal cancer (EO-CRC) incidence increased in the Netherlands with 0.7–2.1% over the last decades. • This increase in incidence was highly comparable to the 50- to 59-year-old population. • EO-CRC treatment and relative survival differed slightly from 50- to 59-year-old patients with CRC. • The urge for a specific approach of EO-CRC in guidelines might be tempered. [ABSTRACT FROM AUTHOR]

The aim of this nationwide cohort study was to examine the course of symptoms and trajectories of health-related quality of life (HR-QoL) and psychological distress during follow-up and to identify vulnerable patients. Patients with pathological stage I–III colorectal cancer (CRC) between 2013 and 2018 were included. Baseline characteristics were collected from the Netherlands Cancer Registry, and patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30/CR29, Hospital Anxiety and Depression Scale and low anterior resection syndrome (LARS) questionnaires at the baseline and subsequently at 3, 6, 12, 18 and 24 months. Latent class growth and multinomial logistic regression analyses were performed to outline 24-month trajectories in HR-QoL and distress and to identify predictive factors. : A total of 1535 patients with colon cancer or rectal cancer were included. Trajectory analysis of HR-QoL identified three patient classes: high HR-QoL (62.7%), improving HR-QoL (29.0%) and low HR-QoL (8.3%). The following patient groups were identified with having low distress (64.0%), moderate distress (26.9%) and high distress (9.1%). Around 13% of the total cohort had either persistent low HR-QoL or high psychological distress throughout follow-up. Patients belonging to this vulnerable group were significantly more likely to be female, to be younger aged, to have lower education, to have disease stage II–III or to have major LARS. Although most patients treated for stage I–III CRC fared well, a small but significant proportion of around 13% did not recover during follow-up and reported low HR-QoL and/or high psychological distress levels throughout. This study's findings should be taken into account when organising and selecting patients for tailored follow-up. • The number of patients with colorectal cancer (CRC) requiring follow-up increased. • Quality of life (QoL) and distress among recently diagnosed patients with CRC are unclear. • Most patients with stage I–III CRC did well and reported high QoL and low distress. • Trajectory analysis revealed vulnerable patient groups and identified predictive factors. • Patient-reported outcome measures should be used when personalising CRC follow-up. [ABSTRACT FROM AUTHOR]

To describe the incidence, treatment and survival of patients with rare types of rectal malignancies in the Netherlands. Data of patients with rectal malignancies diagnosed in the Netherlands between 1989 and 2018 were retrieved from the Netherlands Cancer Registry and grouped according to the RARECARE cancer list. Age-standardised incidence rates were calculated using the European Standard Rate. The Joinpoint Regression Program was used for analysing trends and joinpoints and for the estimation of annual percentage changes (APCs). Patient characteristics, treatment details and relative survival (RS) were reported for different histological types of rectal malignancies and compared between different time periods. RS was assessed using Kaplan-Meier analysis and log-rank test. A total of 88,299 cases of rectal malignancies were included of which 2125 (2.5%) were categorised as rare histological subtypes. The incidence of rectal neuro-endocrine tumours (NET) (APC: 6.2%, 95% confidence interval [CI]: 5.4%; 7.1%), rectal sarcoma (APC: 5.8%, 95% CI: 2.9%; 8.7%) and rectal adenocarcinoma (APC 1.0%, 95% CI: 0.26%; 1.8%) increased. Prognosis was best in patients with rectal NET (5-year RS: 72.4%, 95% CI: 70.1%; 74.7%) and worst in patients with rectal melanoma (5-year RS: 8.9%, 95% CI: 5.1%; 15.7%). RS has improved in patients with rectal adenocarcinoma, rectal sarcoma and rectal lymphoma in 2008–2018 (p-values p < 0.001, p = 0.023 and p = 0.029). Significant increases in incidence were observed for different types of rectal malignancies. Differences in incidence, treatment and survival found in this study could be useful to make clinicians aware of specific diseases. • Rare histological subtypes only account for 2.5% of all rectal malignancies. • Increasing incidence was found in rectal NET, sarcoma and adenocarcinoma. • Therapeutic approaches for rectal cancer are different between specific diseases. • Prognosis of patients with rare types of rectal cancer varies from excellent to poor. • Clinicians should be aware of different histological types of rectal cancer. [ABSTRACT FROM AUTHOR]

• Several factors were associated with 25(OH)D 3 levels in colorectal cancer patients. • Colorectal cancer treatment was the strongest determinant of 25(OH)D 3 levels. • Chemotherapy was associated with decreasing 25(OH)D 3 levels over time. • Vitamin D supplement use was associated with increasing 25(OH)D 3 levels over time. Vitamin D metabolites, including 25-hydroxyvitamin D 3 (25(OH)D 3), may inhibit colorectal cancer (CRC) progression. Here we investigated cross-sectional and longitudinal associations of demographic, lifestyle and clinical characteristics with 25(OH)D 3 serum concentrations in CRC patients at diagnosis and six months later. In 1201 newly-diagnosed stage I-III CRC patients, 25(OH)D 3 levels were analysed twice. Multivariable linear regression was used to assess demographic, lifestyle and clinical determinants of 25(OH)D 3 levels at diagnosis and six months later. Linear mixed models were used to assess characteristics associated with changes in 25(OH)D 3 levels over time. Results of our study showed that vitamin D intake from diet or supplements, use of calcium supplements, BMI and disease stage were associated with 25(OH)D 3 levels at both time points. Six months after diagnosis, gender and having received chemo- and/or radiotherapy were also associated with 25(OH)D 3 levels. A stronger decrease in 25(OH)D 3 levels was observed in patients who underwent chemotherapy, compared to surgery only (β-6.9 nmol/L 95 %CI -9.8; -4.0). Levels of 25(OH)D 3 levels increased in patients using vitamin D supplements compared to non-users (β 4.0 nmol/L 95 %CI 1.2; 6.8). In conclusion, vitamin D supplement use and treatment appear to be important determinants of 25(OH)D 3 levels during the first six months after CRC diagnosis, although the difference in 25(OH)D 3 levels was minor. ClinicalTrials.gov Identifier: NCT03191110 [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the association between pelvic radiation therapy (RT) and the development of rectal cancer as a second primary cancer. Data on patients treated for a primary pelvic cancer between 1989 and 2007 were retrieved from the population-based Netherlands Cancer Registry. Patients treated for more than one pelvic cancer were excluded. To estimate the cumulative incidence of rectal cancer, Fine and Gray's competing risk model was used with death as a competing event. Survival was calculated using multivariable Cox regression. A total of 192,658 patients were included, of which 62,630 patients were treated with RT for their pelvic cancer. Primary tumours were located in the prostate (50.1%), bladder (19.2%), endometrium (13.9%), ovaries (10.0%), cervix (6.4%) and vagina (0.4%). At a median interval of 6 years (range 0–24), 1369 patients developed a rectal cancer. Overall, the risk for rectal cancer was increased in patients who underwent RT for the previous pelvic cancer (subhazard ratio [SHR]: 1.72, 95% confidence interval [CI]: 1.55–1.91). Analysis for each tumour location specifically showed an increased risk in patients who received RT for prostate (SHR: 1.89, 95% CI: 1.66–2.16) or endometrial cancer (SHR: 1.50, 95% CI: 1.13–2.00). A protective effect of RT was observed for patients with bladder cancer (SHR 0.67, 95% CI: 0.47–0.94). There was no survival difference between patients with rectal cancer with or without previous RT (hazard ratio: 0.94, 95% CI: 0.79–1.11). Patients who received RT for a previous pelvic cancer were at increased risk for rectal cancer. The risk was modest and pronounced in patients receiving RT for prostate and endometrial cancer. • Overall, patients receiving pelvic radiation were at increased risk for rectal cancer. • Rectal cancer risk was increased after RT for prostate and endometrial cancer. • No increased risk after RT for bladder, ovarian, cervical and vaginal cancer. • Survival did not differ between patients with rectal cancer with or without previous RT. [ABSTRACT FROM AUTHOR]

Previous studies have shown that older patients benefited less than younger patients from surgical treatment for colorectal cancer (CRC). However, CRC care has advanced over time, and it is time to assess whether the difference in postoperative mortality between older and younger CRC patients is still present. Patients with primary stage I-III CRC diagnosed between 2005 and 2016 were selected from the Netherlands Cancer Registry (N = 111,778). Trends in postoperative mortality and 1-year postoperative relative survival (RS) were analysed, stratified according to age (<75 versus ≥75 years) and tumour location (colon versus rectum). One-year postoperative RS was analysed to correct for background mortality in the older population. Between 2005 and 2016, 30-day postoperative mortality showed a stronger decrease for older patients (from 10.0% to 4.0% for colon cancer [p < 0.001] and from 8.3% to 2.7% for rectal cancer [p < 0.001]) compared with younger patients (from 2.0% to 0.9% for colon cancer [p < 0.001] and from 1.4% to 0.7% for rectal cancer [p = 0.01]). Between 2005 and 2016, also 1-year RS increased more for older patients (from 84.8% to 94.6% for colon cancer and from 86.1% to 97.2% for rectal cancer) compared with younger patients (from 94.0% to 97.8% for colon cancer and from 96.3% to 98.8% for rectal cancer). Between 2005 and 2016, differences in postoperative mortality between older and younger CRC patients decreased. One-year postoperative RS was almost equal for older and younger patients in 2015–2016. This information is crucial for shared decision-making on surgical treatment. • Differences in mortality between older and younger CRC patients decreased. • One-year relative survival became nearly equal for older and younger patients. • Previous literature is no longer representative of the current clinical practice. [ABSTRACT FROM AUTHOR]

Background Hepatic resection and ablative treatments, such as RFA are available treatment options for liver tumors. Advantages and disadvantages of these treatment options in patients with colorectal liver metastases need further evaluation. The purpose of this study was to systematically evaluate the role of radiofrequency ablation (RFA) compared to surgery in the curative treatment of patients with colorectal liver metastases (CRLM). Methods A systematic search was performed from MEDLINE, EMBASE and the Cochrane Library for studies directly comparing RFA with resection for CRLM, after which variables were evaluated. Results RFA had significantly lower complication rates (OR = 0.44, 95% CI = 0.26–0.75, P = 0.002) compared to resection. However, RFA showed a higher rate of any recurrence (OR = 1.66, 95% CI = 1.15–2.40, P = 0.007), local recurrence (OR = 9.56, 95% CI = 6.85–13.35, P = 0.001), intrahepatic recurrence (OR = 1.96, 95% CI = 1.34–2.87, P = 0.001) and extrahepatic recurrence (OR = 1.21, 95% CI = 0.90–1.63, P = 0.22). Also, 5-year disease-free survival (OR = 2.20, 95% CI = 1.28–3.79, P = 0.005) and overall survival (OR = 2.35, 95% CI = 1.49–3.69, P = 0.001) were significantly lower in patients treated with RFA. Conclusions RFA showed a significantly lower rate of complications, but also a lower survival and a higher rate of recurrence as compared to surgical resection. All the included studies were subject to possible patient selection bias and therefore randomized clinical trials are needed to accurately evaluate these treatment modalities. [ABSTRACT FROM AUTHOR]

Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM. [Copyright &y& Elsevier]

Abstract: Background: A noticeable proportion of colorectal cancer (CRC) patients are diagnosed with synchronous CRC. Large population-based studies on the incidence, risk factors and prognosis of synchronous CRC are, however, scarce, and are needed for better determination of risks of synchronous CRC in patients diagnosed with colonic neoplasia. Methods: All newly diagnosed CRC between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands, and studied for synchronous CRC. Results: Of the 13,683 patients diagnosed with CRC, 534 patients (3.9%) were diagnosed with synchronous CRC. The risk of having synchronous CRC was significantly higher in men (OR 1.54, 95% CI 1.29–1.84) and in patients aged >70years (OR 1.83, 95% CI 1.39–2.40). Synchronous CRC patients had a significantly higher risk of distant metastases (OR 1.69, 95% CI 1.27–2.26). In 34% (184/534) the two tumours were located in different surgical segments. Five-year relative survival of synchronous CRC was similar to patients with solitary CRC after multivariate adjustment for the presence of distant metastases. Conclusion: One out of 25 patients diagnosed with CRC presents with synchronous CRC. In the multivariate analysis, survival of patients with synchronous CRC was similar to patients with solitary CRC, when corrected for the presence of distant metastases at first presentation. One third of the synchronous CRC were located in different surgical segments, which stresses the importance of performing total colon examination preferably prior to surgery. [Copyright &y& Elsevier]

Abstract: A total of 11 patients with recurrent rectal cancer who had been previously irradiated were treated with preoperative reirradiation (median dose 30Gy), surgery and IORT. This treatment was related with high morbidity, a short pain-free survival (5 months) and poor local control (27% after 3 years), although some patients have long-term distant control and survival. [Copyright &y& Elsevier]

Objectives: To analyze the clinical features, prognostic factors, and survival of male patients with primary mucosal melanoma on the glans penis, meatus, fossa navicularis, and distal urethra. Methods: We analyzed the clinical features, prognostic factors, and survival of 66 male patients with primary mucosal melanoma on the glans penis, meatus, fossa navicularis, and distal urethra diagnosed over the past 25 years. Data from our series of 19 patients were combined with those of 47 patients reported in the literature. Results: The overall 2 and 5-year survival rates were 63% and 31%, respectively. All patients with nodal and/or distant metastases at presentation died within 2 years. Presence of ulceration, tumor depth of 3.5 mm or more, and tumor diameter greater than 15 mm had a significantly adverse effect on prognosis. Conclusions: The prognosis of primary mucosal penile melanoma is not worse than that for cutaneous melanoma with comparable tumor thickness. Treatment should be similar to that for cutaneous melanoma, with wide radical excision and sentinel node biopsy in clinically lymph node-negative patients. [Copyright &y& Elsevier]

Purpose: To evaluate the initial results of predicting lymph node metastasis in rectal cancer patients detected in-vivo with USPIO-enhanced MRI at 3 T compared on a node-to-node basis with histopathology.Methods: Ten rectal cancer patients of all clinical stages were prospectively included for an in-vivo 0.85 mm3 isotropic 3D MRI after infusion of Ferumoxtran-10. The surgical specimens were examined ex-vivo with an 0.29 mm3 isotropic MRI examination. Two radiologists evaluated in-vivo MR images with a classification scheme to predict lymph node status. Ex-vivo MRI was used for MR-guided pathology and served as a key link between in-vivo MRI and final histopathology for the node-to-node analysis.Results: 138 lymph nodes were detected by reader 1 and 255 by reader 2 (p = 0.005) on in-vivo MRI with a median size of 2.6 and 2.4 mm, respectively. Lymph nodes were classified with substantial inter-reader agreement (κ = 0.73). Node-to-node comparison was possible for 55 lymph nodes (median size 3.2 mm; range 1.2-12.3), of which 6 were metastatic on pathology. Low true-positive rates (3/26, 11 % for both readers) and high true negative rates were achieved (14/17, 82 %; 19/22, 86 %). Pathological re-evaluations of 20 lymph nodes with high signal intensity on USPIO-enhanced MRI without lymph node metastases (false positives) did not reveal tumor metastasis but showed benign lymph node tissue with reactive follicles.Conclusions: High resolution MRI visualizes a large number of mesorectal lymph nodes. USPIO-enhanced MRI was not accurate for characterizing small benign versus small tumoral lymph nodes in rectal cancer patients. Suspicious nodes on in-vivo MRI occur as inflammatory as well as metastatic nodes. [ABSTRACT FROM AUTHOR]