Perioperative management and anaesthetic considerations in pelvic exenterations using Delphi methodology: Results from the PelvEx Collaborative

Background: The multidisciplinary perioperative and anaesthetic management of patients undergoing pelvic exenteration is essential for good surgical outcomes. No clear guidelines have been established, and there is wide variation in clinical practice internationally. This consensus statement consolidates clinical experience and best practice collectively, and systematically addresses key domains in the perioperative and anaesthetic management. Methods: The modified Delphi methodology was used to achieve consensus from the PelvEx Collaborative. The process included one round of online questionnaire involving controlled feedback and structured participant response, two rounds of editing, and one round of web-based voting. It was held from December 2019 to February 2020. Consensus was defined as more than 80 per cent agreement, whereas less than 80 per cent agreement indicated low consensus. Results: The final consensus document contained 47 voted statements, across six key domains of perioperative and anaesthetic management in pelvic exenteration, comprising preoperative assessment and preparation, anaesthetic considerations, perioperative management, anticipating possible massive haemorrhage, stress response and postoperative critical care, and pain management. Consensus recommendations were developed, based on consensus agreement achieved on 34 statements. Conclusion: The perioperative and anaesthetic management of patients undergoing pelvic exenteration is best accomplished by a dedicated multidisciplinary team with relevant domain expertise in the setting of a specialized tertiary unit. This consensus statement has addressed key domains within the framework of current perioperative and anaesthetic management among patients undergoing pelvic exenteration, with an international perspective, to guide clinical practice, and has outlined areas for future clinical research

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: Study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods: Thismulticentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2- week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged usingMRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8Gy in radiotherapy-naive patients, and 15 × 2.0Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-termoncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion: This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative

At presentation, 15-20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection