Session Item

The treatment of locally recurrent rectal cancer (LRRC) is challenging as excessive surgery is often needed to obtain radical resection. Neoadjuvant radiotherapy (RT) has been introduced to improve rates of radical surgery. However, patients with LRRC have often received RT as a part of the primary treatment strategy. Pelvic re-irradiation (re-RT) has proven feasible mainly in retrospective series, but it may increase the risk of acute and late toxicities. We conducted the first prospective study to evaluate re-RT with modern hyperfractionated intensity-modulated radiation therapy (IMRT) in previously irradiated LRRC patients. The primary endpoint was a radical resection (R0) rate of 50 %, and secondary endpoints included recurrence-free survival (RFS), overall survival (OS), and toxicity.

Previously irradiated patients with potentially resectable LRRC were included in a prospective, multicentre, phase II trial from 2015 to 2019. Re-RT was delivered with hyperfractionated, accelerated IMRT using 40.8 Gy in 1.2 Gy twice daily guided by cone-beam CT ± concomitant capecitabine 825 mg/m2 BID. Primary RT plans supported re-RT planning according to the ALARA principle for normal tissue. Re-evaluation of resectability was performed 4-6 weeks after re-RT, surgery was performed within 3 weeks when feasible. Toxicity was graded according to NCI-CTCAE (version 4.0) acute (during RT), post-RT (from the end of RT to surgery), and post-OP (within 6 months from surgery).

Sixteen patients were included (median age: 68 years, male: 9, female: 7, performance status 0-1: 93.8 %). Median primary RT dose was 50 Gy, (range 25-60 Gy). Median re-treatment interval was 3.74 years (95 %CI: 2.73-4.73).  Median re-RT dose was 40.8 Gy (range, 37.2-45). After re-RT 68.8 % (n=11) patients underwent surgery. R0 was obtained in 27.3 % (n=3/11), R1 in 64 % (n=7/11), and R2 in 9.1% (1/11). Of the remaining, one had a complete response (CR) and proceeded to a wait and watch approach, and four proceeded to palliative treatment due to liver metastasis (n=1) or progression of the local tumour with no surgical offer at re-evaluation (n=3). The highest reported acute haematologic toxicity was grade 2 anaemia (n=2). Post-RT grade ≥ 3 toxicity was reported for three patients (subileus, dysphagia, and urinary tract infection), and post-OP ≥ grade 3 toxicity was reported for two patients (wound infection and pelvic abscess). At a median follow-up of 54 months, the median RFS was 15.8 months (95 % CI, 9.2-23.2). Median OS from the first fraction of re-RT was 47 months, with a 1, 3, and 5-year survival rate of 81.3 %, 56.3 %, and 25.7 %, respectively. The median OS in patients with CR/R0/R1 was 51 months compared to 12 months for R2/non-resected patients.

Neo-adjuvant hyperfractionated re-irradiation of LRRC is feasible. Due to the manageable acute toxicity dose escalation could be pursued within clinical trials to enhance oncological outcomes.