Objective: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. Summary of Background Data: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives.Methods: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. Results: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay ]. The impact of individual complications on unplanned readmission was smaller than 11%. Conclusion: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying.

Introduction: Since current studies on locally advanced pancreatic cancer (LAPC) mainly report from single, high-volume centers, it is unclear if outcomes can be translated to daily clinical practice. This study provides treatment strategies and clinical outcomes within a multicenter cohort of unselected patients with LAPC. Materials and methods: Consecutive patients with LAPC according to Dutch Pancreatic Cancer Group criteria, were prospectively included in 14 centers from April 2015 until December 2017. A centralized expert panel reviewed response according to RECIST v1.1 and potential surgical resectability. Primary outcome was median overall survival (mOS), stratified for primary treatment strategy. Results: Overall, 422 patients were included, of whom 77% (n ¼ 326) received chemotherapy. The majority started with FOLFIRINOX (77%, 252/326) with a median of six cycles (IQR 4e10). Gemcitabine monotherapy was given to 13% (41/326) of patients and nab-paclitaxel/gemcitabine to 10% (33/326), with a median of two (IQR 3e5) and three (IQR 3e5) cycles respectively. The mOS of the entire cohort was 10 months (95%CI 9e11). In patients treated with FOLFIRINOX, gemcitabine monotherapy, or nab-paclitaxel/ gemcitabine, mOS was 14 (95%CI 13e15), 9 (95%CI 8e10), and 9 months (95%CI 8e10), respectively. A resection was performed in 13% (32/252) of patients after FOLFIRINOX, resulting in a mOS of 23 months (95%CI 12e34). Conclusion: This multicenter unselected cohort of patients with LAPC resulted in a 14 month mOS and a 13% resection rate after FOLFIRINOX. These data put previous results in perspective, enable us to inform patients with more accurate survival numbers and will support decision-making in clinical practice.

This study assessed the margins needed to cover tumor intrafraction motion during an MRguided radiotherapy (MRgRT) dose-escalation strategy in intermediate risk rectal cancer. Methods: Fifteen patients with rectal cancer were treated with neoadjuvant short-course radiotherapy, 5x5 Gy, according to an online adaptive workflow on a 1.5 T MR-linac. Per patient, 26 3D T2 weighted MRIs were made; one reference scan preceding treatment and five scans per treatment fraction. The primary tumor was delineated on each scan as gross tumor volume (GTV). Target coverage margins were assessed by isotropically expanding the reference GTV until more than 95% of the voxels of the sequential GTVs were covered. A margin with a coverage probability threshold of 90% was defined as adequate. Intra-and interfraction margins to cope with the movement of the GTV in the period between scans were calculated to indicate the target volume margins. Furthermore, the margin needed to cover GTV movement was calculated for different time intervals. Results: The required margins to cover inter-and intrafraction GTV motion were 17 mm and 6 mm, respectively. Analysis based on time intervals between scans showed smaller margins were needed for adequate GTV coverage as time intervals became shorter, with a 4 mm margin required for a procedure of 15 min or less. Conclusion:The shorter the treatment time, the smaller the margins needed to cover for the GTV movement during an online adaptive MRgRT dose-escalation strategy for intermediate risk rectal cancer. When time intervals between replanning and the end of dose delivery could be reduced to 15 min, a 4 mm margin would allow adequate target coverage.

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Aim A prolonged interval (>4 weeks) between short‐course radiotherapy (25 Gy in five fractions) (SCRT‐delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient‐reported bowel dysfunction and physician‐reported radiation‐induced toxicity for 8 weeks following SCRT‐delay. Method Patients who were referred for SCRT‐delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient‐reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician‐reported radiation‐induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. Results Fifty‐one patients were included; 31 (61%) were men and the median age was 67 years (range 44–91). Patient‐reported bowel dysfunction and physician‐reported radiation‐induced toxicity peaked at weeks 1–2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT‐delay. Grade 3 radiation‐induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4–5 radiation‐induced toxicity occurred. Conclusion During SCRT‐delay, almost every patient experiences temporary mild–moderate radiation‐induced toxicity and major LARS, but life‐threatening toxicity is rare. SCRT‐delay is a safe alternative to SCRT‐direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.

Background Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4–8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database. Methods Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)–) N0 M0 and T1–3(MRF–) N1 M0) treated with either SCRT-delay (4–12 weeks) or SCRT-direct surgery in 2018–2021 were selected from a Dutch national colorectal cancer database. Confounders were adjusted for using inverse probability of treatment weighting (IPTW). The primary endpoint was the 90-day postoperative complication rate. Secondary endpoints included the pCR rate. Endpoints were compared using log-binomial and Poisson regression. Results Some 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable after SCRT-direct surgery and SCRT-delay (40.1 versus 42.3 per cent; risk ratio (RR) 1.1, 95 per cent c.i. 0.9 to 1.3). A pCR occurred more often after SCRT-delay than SCRT-direct surgery (10.7 versus 0.4 per cent; RR 39, 11 to 139). Conclusion There was no difference in surgical complication rates between SCRT-delay and SCRT-direct, but SCRT-delay was associated with more patients having a pCR.

Background In minimally invasive surgery of the sigmoid colon and rectum a retractor sponge has been introduced as an alternative to the Trendelenburg position. This randomized clinical trial (RCT) compared postoperative duration of hospital stay and perioperative outcomes in patients with sigmoid or rectal cancer undergoing sponge-assisted versus Trendelenburg position surgery. Methods The SPONGE trial is a single-centre RCT nested within the Dutch nationwide prospective observational cohort of patients with colorectal cancer, and follows the Trials within Cohorts (TwiCs) design. Patients with sigmoid or rectal cancer undergoing elective laparoscopic or robotic surgery were randomized to either sponge-assisted or Trendelenburg surgery on a 1:1 basis using block randomization. Duration of postoperative hospital stay was the primary outcome and was compared using the Mann–Whitney U test. Secondary endpoints included the proportion of complications, readmissions, or mortality versus the χ2 test in intention-to-treat and per-protocol analyses. This trial was not blinded for patients in the intervention arm or physicians. Results Between November 2015 and June 2021, 82 patients were randomized to sponge-assisted surgery and 81 to Trendelenburg surgery. After post-randomization exclusion, 150 patients remained for analyses (75 patients per arm). There was no statistically significant difference in median duration of hospital stay (5 days versus 4 days, respectively; P = 0.06), 30-day postoperative complications (30 per cent versus 31 per cent; P = 1.00), readmission rate (8 per cent versus 15 per cent; P = 0.30), or mortality (0 per cent versus 1 per cent, P = 1.00). The per-protocol analysis showed similar results. No adverse device events were seen. Conclusion Sponge-assisted laparoscopic/robotic surgery does not reduce the duration of hospital stay, or perioperative morbidity or mortality. Trial registration NCT02574013 (http://www.clinicaltrials.gov)