Could increasing the dose of radiation following preoperative chemoradiation for advanced rectal cancer improve surgical outcomes? Clatterbridge experience with HDR brachytherapy boost: Preliminary results
Authors: Sun Myint A. , Lee C. , Wong H. , Haylock B. 
Published: March 2020

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Introduction: Preoperative radiotherapy has been shown to improve local control in advanced rectal carcinoma compared to surgery alone. Recent large randomised trials have confirmed that chemoradiotherapy (CRT) was better than radiotherapy alone. This pilot study was designed to increase the radiation dose by using High dose rate (HDR) brachytherapy boost following preoperative CRT to evaluate whether this strategy improve surgical outcomes, without increase in toxicity. Methods: Since, October 2004 we have used the new Nucletron rectal HDR applicator for brachytherapy boost in 12 patients following pre-op CRT. The patients were staged by CT and MRI Scans. All had locally advanced disease either bulky low T2 or T3 with threatened CRM and multiple suspicious lymph nodes. They were offered preoperative chemoradiotherapy using either 5FU infusion 1G/m2 day 1–4 (wk 1+5) or oral Capecitabine 825mg/m2 Mon-Fri for 5 weeks together with CT planned external beam RT 45Gy in 25 fraction over 5 weeks. Those downstaged on repeat MRI scan were offered additional HDR Boost 10Gy directly to the tumour followed by surgery 6–8 weeks later. Results: Evaluation was done on the first 12 patients. Eleven males and 1 female. Median age 68 (range50–80 years). PS 0–1. Clinical stages at presentation were cT2 in two patients and cT3 in 10 patients. No suspicious lymph nodes in 2 and cN1 in 10 patients. Eleven patients had chemoradiotherapy and one had radiotherapy alone. All patients completed treatment without interruptions. Anterior resection was carried out in 6 patients and 6 had APR. All patients had RO resection (100%) compared to 60–80% with conventional preoperative chemoradiotherapy using 5FU ± Irinotecan or Oxaliplatin regimes. Pathological complete remission pCR was achieved in 6 patients (50%) compared to 12–30% with conventional CRT. There was no increase in G3–4 toxicity from HDR boost and no delay in wound healing or anastamotic leakages. Discussion: Pre operative chemoradiotherapy using 5FU regimes had shown improvement in local control compared to radiotherapy alone but so far, none of the trials showed survival benefit. Newer novel agent such as Irinotecan or Oxaliplatin has been used in addition to 5FU or capecitabine for the pre operative chemoradiotherapy regimes in an attempt to improve surgical out comes. However, there were increased in radiation related G3–4 complications up to 30%. This study has shown that Increasing the dose of radiation by HDR Brachytherapy boost appears to improve the RO resection rates compared to conventional CRT and also increased in pCR rates. The follow up is still too short to evaluate whether there is improvement in DFS but based on previous CRT studies, the local control rate is predicted to improve further without added toxicity. We plan to extend this study to compare this strategy in a randomised phase 3 trial with conventional chemoradiotherapy in patients who are not fit for more intensive chemoradiotherapy using triplet regimes. This approach is suitable for elderly or medically compromised patients who are not fit for intensive chemoradiotherapy with newer agents.

No significant financial relationships to disclose.