Quality of Life Analysis of a Phase II Randomized Controlled Trial Comparing 3D-Conformal Radiotherapy (3D-CRT) and Intensity Modulated Radiotherapy (IMRT) in Locally Advanced Rectal Cancer (TRI-LARC)

Abstract

<h3>Purpose/Objective(s)</h3> The aim of the study was to compare the use of 3D-CRT and IMRT in pre-operative long course chemo-radiotherapy for locally advanced rectal cancer. We herein evaluate the impact of the two treatment modalities on quality of life (QOL), a secondary objective of the study. <h3>Materials/Methods</h3> 94 patients with rectal adenocarcinoma were enrolled in a prospective randomized phase II trial across three institutions between 2014 and 2020. Eligible patients had stage T3-4, N(any) or circumferential resection margin at risk with no evidence of metastatic disease. All patients were prescribed 50.4Gy in 28 fractions with concomitant 5-fluorouracil or capecitabine. Patients were randomly assigned (1:1) to 3D-CRT and IMRT planning techniques. QOL was assessed using the EORTC QLQ C30 and QLQ CR29 questionnaires at baseline, during the final week of radiotherapy and at six and twelve months after radiotherapy. A paired sample t test was used to compare differences in QOL from baseline to each follow-up. One-way between-group analyses of covariance (ANCOVA) were conducted to compare the effect of the trial arms on each QOL score. <h3>Results</h3> At a median follow-up of 14 months, the trial was terminated early due to failure to establish efficacy in the primary outcome, acute gastrointestinal toxicity. The median age was 59 years and 72/94 (77%) were male. 86/94 (91%) patients completed the baseline and at least one other QOL assessments. QOL data at one year was available in 55/94(58%). At baseline, there was no difference in QOL scores between trial arms. Overall, emotional functioning had improved at six months but physical, cognitive, role and social functioning had declined. At six months, there was a significant improvement in constipation, blood and mucous in stool, bloating, urinary frequency, buttock pain and anxiety scores compared to baseline. There was a significant deterioration in dyspnea, fatigue, nausea/vomiting, taste, hair loss, erectile dysfunction, body image and global health scores from baseline to 6-month follow-up. After adjusting for pre-intervention score, the IMRT arm had better physical functioning (p=0.038) and role functioning (p=0.014) during the final week of radiotherapy compared to the 3DCRT arm. The end of radiotherapy embarrassment score, for those without a stoma, was significantly worse in the IMRT arm (p=0.032). There was no other significant difference in QOL scores between the two arms, at either the final week of radiotherapy or at 6 months, after adjustment for pre-intervention scores. The limitations of the study include its early termination, the potential for type 1 error and the possible influence of other factors on QOL data such as chemotherapy and postoperative complications. <h3>Conclusion</h3> There are limited QOL benefits of IMRT compared to 3D-CRT in the neoadjuvant setting for rectal cancer.