Improved outcomes for responders to induction chemotherapy 37 CHAPTER 3 Surgery and pathology The type of surgery depended on the location of the recurrence and involvement of adjacent structures and was performed by experienced surgical oncologists. In accordance with the type of reconstructions, other specialists, such as a urologist or a plastic surgeon, were consulted. When assessed as necessary and feasible, e.g., when there was tumour adherence or no adequate soft tissue margin for a clear resection margin, intraoperative electron beamradiotherapy (IOERT) was administered in a dose of 10–12.5 Gy. Synchronous metastases were treated during the waiting time between (chemo) radiotherapy and surgery or after surgery. Treatment consisted of local resection or otherwise local therapy, including radiofrequency ablation, microwave ablation, or stereotactic radiotherapy. Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C was administered peroperative in case of limited peritoneal metastases. Pathologic specimens were revised by a specialized pathologist. Pathologic response was scored according to the Mandard classification.17 For survival analyses, pathologic response was categorized as ‘complete’ (Mandard 1), ‘good’ (Mandard 2–3), or ‘poor’ response (Mandard 4–5). An R0 resection was defined as a resection without tumour cells in any of the resection margins. An R1 resection was considered a resection with microscopically involved margins, and an R2 resection was considered a gross incomplete resection. Study endpoints Endpoints were pathologic response, resection margin and overall, local recurrence free, metastasis free, and disease free survival, as well as toxicity and complications caused by the treatment regimen. Overall survival (OS) was calculated from the date of start treatment until the date of death from any cause or censored at last follow-up. Local recurrence free survival (LRFS) was calculated from the date of surgery until the date of local recurrence detected by imaging or histology or censored at last follow-up or death. Metastasis free survival (MFS) was calculated from the date of surgery until the date of histologically or radiologically proven distant metastases or censored at last follow-up or death. Disease-free survival (DFS) was calculated from the date of surgery until the date of local recurrence or distant metastases or censored at last follow-up or death. Toxicitywas retrospectively scored according to theCommonToxicityCriteria of theNational Cancer Institute, and complications were scored according to the Clavien– Dindo classification.18,19
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