Purpose: To assess the safety and long-term outcome of a multimodality treatment consisting of radical surgery, intra-operative radiotherapy (IORT), and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with locally advanced rectal cancer (LARC) or locally recurrent rectal carcinoma (LRRC) and peritoneal metastases (PM). Methods: The present study was a single-center cohort study, including all consecutive patients undergoing this treatment in a tertiary referral center for LARC, LRRC, and PM. Postoperative complications, intensive care stay (ICU stay), and re-admission rates were assessed as well as disease-free survival (DFS) and overall survival (OS). Results: A total of 14 LARC and 16 LRRC patients with PM were included in the study. The median ICU stay was 1 day, and 57% of patients developed a severe postoperative complication. No 90-day mortality was observed. Median DFS was 10.0 months (Interquartile Range 7.1–38.7), and median OS was 31.0 months (Interquartile Range 15.9–144.3). Conclusions: As postoperative complications and survival were in line with treatments that are accepted for LARC or LRRC and PM as separate procedures, we conclude that combined treatment with IORT and CRS-HIPEC should be considered as a treatment option for selected patients with LARC or LRRC and peritoneal metastases in tertiary referral centers.

In patients with resectable colorectal peritoneal metastases, it is unclear whether systemic chemotherapy, in addition to cytoreductive surgery‐hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC), improves overall survival (OS). This systematic review of 12 retrospective studies involving 3721 patients aimed to summarize the available evidence. Contradictory results were found regarding the effectiveness of neoadjuvant, adjuvant, and perioperative systemic therapies on OS, with a high risk of bias. Available evidence remains inconclusive, stressing the need for prospective, randomized trials, like the ongoing Dutch CAIRO6‐trial.

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) offers a localized palliative treatment option for patients with colorectal peritoneal metastases (CPM), often combined with systemic therapy to maximize anti-tumor efficacy. This study on the pharmacokinetics of oxaliplatin-based PIPAC with electrostatic precipitation (ePIPAC-OX) aimed to determine the absolute bioavailability of oxaliplatin in plasma after ePIPAC-OX with reference to systemic therapy and to gain insights for optimizing therapy. Methods: This analysis included patients of the recently published CRC-PIPAC-II study, who received three cycles of oxaliplatin-based systemic therapy and ePIPAC-OX for unresectable CPM. Whole-blood and plasma ultrafiltrate samples were collected at five to six time points after both intravenous oxaliplatin and ePIPAC-OX. Pharmacokinetics were analyzed using population modeling. Absolute bioavailability was calculated as the fraction of the Area under the Curve (AUC0-∞) of the systemic oxaliplatin exposure after intraperitoneal administration over the AUC after intravenous administration, corrected for the dose. Results: The study included 18 patients, mostly treated with capecitabine and oxaliplatin (CAPOX) and bevacizumab (15 patients). The median dose-uncorrected AUC of systemic oxaliplatin and ePIPAC-OX in plasma was 165.2 μg*h/mL and 57.4 μg*h/mL, respectively. The median bioavailability of the total concentration and free fraction of oxaliplatin after ePIPAC-OX were both 48 % (interquartile range [IQR] 42–57 %). Dose reduction due to toxicity was required for eight patients (44 %). All the included patients experienced short-term symptoms of acute sensory neuropathy, with eight cases occurring after ePIPAC-OX. Conclusion: This is the first study to examine the absolute bioavailability of oxaliplatin administered by ePIPAC-OX in humans, using intra-patient data as a control measurement. The systemic bioavailability of oxaliplatin was substantial after ePIPAC-procedures. Therefore, ePIPAC-OX cannot be considered as solely a local treatment. Future research should take this into account for patients treated with both systemic chemotherapy and ePIPAC-OX as bidirectional therapy.