Successful downstaging of high rectal and recto-sigmoid cancer by neo-adjuvant chemo-radiotherapy

Abstract

Purpose: The benefit of neoadjuvant therapy for tumours above the peritoneal reflection is not clear. The purpose of this study is to demonstrate the feasibility and downstaging of treating locally advanced tumours from high rectum to distal sigmoid with preoperative chemoradiotherapy (CRT).

Methods and materials: Seventeen patients with high rectal, rectosigmoid or distal sigmoid tumours above the peritoneal reflection received neoadjuvant CRT, selected on MRI findings indicating T4 disease or threatened circumferential resection margin. All patients were administered neoadjuvant chemotherapy, with Oxaliplatin or Mitomycin C and a Fluoropyrimidine. The pelvis received long-course CT-planned conformal RT, 45 Gy in 25 fractions, with a boost of 5.4-9 Gy in 3-5 fractions. Thirteen patients were treated with concomitant oral or intravenous Fluoropyrimidine chemotherapy.

Results: Median follow-up was 37 months. Overall survival was 82.35% (95% Confidence Interval (CI) 54.7-93.9) and disease free survival 81.25% (95% CI 52.5-93.5). Only 1 patient suffered loco-regional relapse. Chemotherapy regimens were well tolerated, though some patients required dose reductions. Nine patients (52.9%) lowered pathologic disease AJCC stage, i.e. 'downstaged'. Six patients (35.3%) achieved complete pathological response. Clear margins were attained in all but 1 patient. Three patients were converted from cT4 to ypT3. No patient required a gap during CRT. One patient suffered a grade III acute toxicity, but no grade IV (RTOG). There were 3 grade III and 3 grade IV late toxicities (LENT-SOMA).

Conclusions: Locally advanced high rectal and recto-sigmoid tumours may be treated with pre-operative CRT with acceptable toxicity, impressive down-staging, and clear surgical margins.

Keywords: chemoradiotherapy; chemotherapy; downstaging; radiotherapy; total mesorectal excision.

Figure 1

Axial and Sagittal phase I planning CT showing planning target volume (thick line) and 95% isodose (thin line). Note a higher than standard superior border to cover primary disease with a 3 cm margin.

Figure 2

Axial and Sagittal phase II planning CT showing planning target volume (thick line) and 95% isodose (thin line). Note a 2 cm margin around the gross tumour volume (including nodal disease in the mesorectum), with anterior sacrum included.

Figure 3

Patient 1: Sagittal T2 weighted fast spin echo (TR3900 TE 120) MRI scans of a) pre-chemoradiotherapy, showing a large rectal tumour (open arrow) almost entirely above the peritoneal reflection (arrow), and b) marked tumour regression and downsizing 4 weeks post-chemoradiotherapy, with areas of low signal intensity indicating fibrosis (open arrow).

Figure 4

Patient 1: Coronal oblique imaging axial to Recto—Sigmoid, T2 weighted fast spin echo (TR4000 TE 120) MRI scans demonstrating: evidence of Recto-Sigmoid adenocarcinoma downstaging with neoadjuvant chemoradiotherapy. a) Annular tumour invading extensively into the mesorectum, with a threatened circumferential surgical margin (arrow) and tumour also appears to have perforated through the peritoneal reflection (open arrow). Preoperative chemoradiotherapy was administered. b) Scans 4 weeks following completion of therapy. There has been remarkable tumour regression, with low signal intensity indicating fibrosis (arrow) and margins no longer appear threatened. There is fibrosis (low signal intensity) at the peritoneal reflection. c) Surgical specimen confirms fibrosis (arrows). This was an R0 resection.

Figure 5

Patient 2: Sagittal T2 weighted fast spin echo (TR3900 TE 120) MRI scans of a) pre-chemoradiotherapy, showing a large rectal tumour (open arrow) arising entirely above the peritoneal reflection (arrowed) into the sigmoid colon, almost to the level of S1/2, and b) considerable tumour regression and downsizing 4 weeks post-chemoradiotherapy, with extensive low signal intensity indicating fibrosis (open arrow), consistent with a radiological complete response.

Figure 6

Patient 2: Oblique axial T2 weighted fast spin echo (TR4000 TE 120) MRI scans demonstrating evidence of Recto-Sigmoid adenocarcinoma downstaging with neoadjuvant chemoradiotherapy. a) Near circumferential tumour abuts (arrowed) the peritoneal surface and fibroid uterus. Preoperative chemoradiotherapy was delivered. b) Scans 4 weeks following completion of therapy. There has been very considerable tumour regression, with extensive low signal intensity indicating fibrosis (arrowed). Appearances are in keeping with a radiological complete response. c) Surgical specimen confirms fibrosis (arrowed) and was a pathological complete response.