Chapter 8 146 Asmall group of LRRCpatients have not received radiotherapy for their primary tumour and the tumour cells in the recurrence have not developed radioresistancy. The general consensus is that these radiotherapy naive LRRC patients can be treated as primary advanced rectal cancer patients with full course chemoradiation before surgical resection. In these patients the highest clear resection margin rates and best 5-year survival rates can be obtained. Unfortunately, most LRRC patients are not radiotherapy naive and cannot receive full course chemoradiation. The debate how to treat these patients either by upfront surgery or re-irradiation with a boost and combined with systemic treatment has not been decided. Reirradiation Mohiuddin was the first to investigate the efficacy and safety of re-irradiation in LRRC patients who were not radiotherapy naive. In 1993 he published a phase 1-2 study establishing that a 30-40 Gy hypo-fractionated was safe and effective.5 His long term results of re-irradiation with 30 Gy and supplementary boost of 6 Gy did show a tumour response was present in up to 50 percent of patients, both in curative as palliative setting. A median survival of 44 months versus 14 months was found for resected and unresected patients after re-irradiation respectively.6 In a multicentre phase 2 study, Valentini showed a response rate of 48 percent and even pathological complete response rate of 8.5 percent after re-irradiation and resection, without grade 4 toxicity.7 In the Catharina Hospital Eindhoven (CHE) a LRRC programme was started in 1994 and in 1997 re-irradiation became the standard. In 2008 first results showed that that reirradiation with a supplementary intraoperative electron beam boost (IOERT) resulted in significant better survival compared to the first group of patients who were not reirradiated.8 It was also clear that the improved outcome was directly related to the higher clear resection margin rate. After reirradiation the clear resection margin rate was 65 percent for reirradiated versus 29 percent for non-reirradiated patients. In an update of the CHE data in 2014 no survival difference between the reirradiation and full course chemoradiation group of LRRC patients was observed. More importantly, no difference in pre- and postoperative complication rate was found.9 In a large cohort study of the pooled data of the CHE and Mayo Clinics Rochester of 565 patients with LRRC these findings were confirmed. However, one concerning point remained: despite overall survival comparable to patients who could undergo full course of chemoradiation, the local re-recurrence rate was still higher than in radiotherapy naive patients.10 Since, several systematic reviews of reirradiation in LRRC patients concluded that reirradiation is feasible, safe and effective to increase the clear resection margin rate, which is the single most important factor to improve overall survival in these challenging patients.11,12 In a recent study fromtheMilanNational Cancer Institute, comparing upfront surgery with reirradiation, an improved disease-free survival rate
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