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A prolonged time interval between chemoradiation and total mesorectal excision (TME) may render more rectal cancer patients eligible for organ-sparing approaches but may also cause more pelvic fibrosis and surgical morbidity. We estimated the effect of time interval on postoperative complications and other surgical outcomes in rectal cancer patients. This is a population-based cohort study using data of the Dutch Colorectal Audit. Rectal cancer patients treated with chemoradiation followed by TME after an interval of 3–20 weeks were selected (n = 6,268). Time interval from completion of chemoradiation to TME was categorized into 3–6, 7–8, 9–10, 11–12 and 13–20 weeks. Outcomes included postoperative complication (any, and stratified by medical and surgical complications), reintervention, intraoperative complication, incomplete resection, positive circumferential margin (CRM) and pathological complete response (pCR). The interval of 7–8 weeks was the reference group. Prolonged time intervals were not associated with a higher risk of a postoperative complication (any, surgical or medical), reintervention, and incomplete resection. Intraoperative complications were however more common after 11–12 weeks than after 7–8 weeks (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.20–2.69). The interval of 9–10 weeks was associated with less CRM positive resections, and 9–10 and 13–20 weeks with more pCR (relative to 7–8 weeks, OR = 0.74, 95%CI = 0.56–0.98; OR = 1.28, 95%CI = 1.04–1.58; and OR = 1.33, 95%CI = 1.04–1.71, respectively). Compared with 7–8 weeks, longer time intervals up to 13–20 weeks between chemoradiation and TME are not associated with more postoperative complications or more positive resection margins. Accordingly, prolonging the interval aiming for organ-sparing treatment is safe. [ABSTRACT FROM AUTHOR]

Introduction Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands. Methods In the population based Netherlands Cancer Registry, clinical stage III rectal cancer patients, diagnosed between 2008 and 2014, who underwent CRT or SCTR-delay were selected. pCR (ypT0N0), near pCR (ypT0-1N0), and tumor and nodal downstaging were compared between the treatment groups using multivariable logistic regression analysis. Results 386 patients underwent SCRT-delay and 3659 patients underwent CRT. The pCR-rate in the SCRT-delay group was significantly lower compared to the CRT-group (6.4% vs. 16.2%, p < 0.001). After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, SCRT-delay patients were significantly less likely to reach pCR (adjusted odds ratio 0.3, 95%CI 0.2–0.5). Also, near-pCR (ypT0–1N0) as well as tumor and nodal downstaging was observed less often in the SCRT-delay group. Conclusion Compared to patients treated with neoadjuvant CRT, those receiving SCRT and delayed surgery are less likely to develop pCR. Novel neoadjuvant treatment strategies for patients not fit enough for CRT are needed to increase their eligibility for organ-sparing treatments. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy has been advised for high-risk stage II and III colon cancer since 2004. After the IDEA study showed no clinically relevant difference in outcome, reduction of adjuvant CAPOX duration from 6 to 3 months was rapidly adopted in the Dutch treatment guideline in 2017. This study investigates the real-world impact of the guideline change on overall survival (OS) and patient-reported outcomes (PROs). Patients with high-risk stage II (pT4 +) and III (pN+) colon cancer were selected from the Netherlands Cancer Registry, based on surgical resection and adjuvant CAPOX before (2015–2016) versus after (2018–2019) the guideline change. Both groups were compared on OS, using multivariable Cox regression, and on PROs. Patients treated before (n = 2330) and after (n = 2108) the guideline change showed similar OS (HR 1.02; 95 %CI [0.89–1.16]), also in high-risk stage III (pT4/N2, HR 1.06 [0.89–1.26]). After the guideline change, 90 % of patients were treated for 3 months with no inferior OS to those still receiving 6 months (HR 0.89 [0.66–1.20]). PROs 2 years after CAPOX completion, available for a subset of patients, suggest a lower neuropathy (n = 366; 26.2 [21.3–31.1] to 16.5 [14.4–18.6]) and better quality of life (n = 396; 80.9 [78.6–83.2] to 83.9 [82.8–84.9]), but no significant difference in workability (n = 120; 31.5 [27.9–35.1]) to 35.3 [33.8–36.7]), with reduction from 6 to 3 months of CAPOX. This real-world study confirmed that shorter adjuvant CAPOX did not compromise OS and may improve PROs, complementing the IDEA study and supporting 3 months of adjuvant CAPOX in daily clinical practice. • Guideline change from 6 to 3 months of adjuvant CAPOX resembled a natural experiment. • Real-world overall survival before and after the guideline change was comparable. • Even in high-risk stage III colon cancer, survival was not worse after 3 months CAPOX. • Long-term neurotoxicity was lower and quality of life was better after 3 months CAPOX. [ABSTRACT FROM AUTHOR]

Purpose: Pathologic complete tumor response after chemoradiation in patients with locally advanced rectal cancer (LARC) is associated with a favorable prognosis and allows organ-sparing treatment strategies. In the RECTAL-BOOST trial, we aimed to investigate the effect of an external radiation boost to the tumor before chemoradiation on pathologic or sustained clinical complete tumor response in LARC.Methods and Materials: This multicenter, nonblinded, phase 2 randomized controlled trial followed the trials-within-cohorts design, which is a pragmatic trial design allowing cohort participants to be randomized for an experimental intervention. Patients in the intervention group are offered the intervention (and can either accept or refuse this), whereas patients in the control group are not notified about the randomization. Participants of a colorectal cancer cohort referred for chemoradiation of LARC to either of 2 radiation therapy centers were eligible. Patients were randomized to no boost or an external radiation boost (5 × 3 Gy) without concurrent chemotherapy, directly followed by standard pelvic chemoradiation (25 × 2 Gy with concurrent capecitabine). The primary outcome was pathologic complete response (ie, ypT0N0) in patients with planned surgery at 12 weeks, or, as surrogate for pathologic complete response, a 2-year sustained clinical complete response for patients treated with an organ preservation strategy. Analyses were intention to treat. The study was registered with ClinicalTrials.gov, number NCT01951521.Results: Between September 2014 and July 2018, 128 patients were randomized. Fifty-one of the 64 (79.7%) patients in the intervention group accepted and received a boost. Compared with the control group, fewer patients in the intervention group had a cT4 stage and a low rectal tumor (31.3% vs 17.2% and 56.3% vs 45.3%, respectively), and more patients had a cN2 stage (59.4% vs 70.3%, respectively). Rate of pathologic or sustained clinical complete tumor response was similar between the groups: 23 of 64 (35.9%; 95% confidence interval [CI], 24.3-48.9) in the intervention group versus 24 of 64 (37.5%; 95% CI, 25.7-50.5) in the control group (odds ratio [OR] = 0.94; 95% CI, 0.46-1.92). Near-complete or complete tumor regression was more common in the intervention group (34 of 49; 69.4%) than in the control group (24 of 53; 45.3%; (OR = 2.74, 95% CI 1.21-6.18). Grade ≥3 acute toxicity was comparable: 6 of 64 (9.4%) in the intervention group versus 5 of 64 (7.8%) in the control group (OR = 1.22; 95% CI, 0.35-4.22).Conclusions: Dose escalation with an external radiation therapy boost to the tumor before neoadjuvant chemoradiation did not increase the pathologic or sustained clinical complete tumor response rate in LARC. [ABSTRACT FROM AUTHOR]