[Chronic radiation-induced rectal injury after adjuvant radiotherapy for pelvic malignant tumors: report based on a phase 3 randomized clinical trial].

Radiotherapy is one of the standard treatments for pelvic malignant tumors. However, researches associated with intestinal radiation injury and the quality of life (QoL) of patients receiving radiotherapy were lacking in the past. This study aims to analyze the occurrence of radiation-induced rectal injury after adjuvant radiotherapy for pelvic malignant tumors and call for more attention on this issne. A retrospectively observational study was conducted. Case data of cervical cancer patients from the database of STARS phase 3 randomized clinical trial (NCT00806117) in Sun Yat-sen University Cancer Center were analyzed. A total of 848 cervical cancer patients who received adjuvant radiation following hysterectomy and pelvic lymphadenectomy in Sun Yat-sen University Cancer Center from February 2008 to August 2015 were recruited. The pelvic radiation dosage was 1.8 Gy/day or 2.0 Gy/day, five times every week, and the total dosage was 40-50 Gy. Among 848 patients, 563 patients received radiation six weeks after surgery, of whom 282 received adjuvant radiation alone and 281 received concurrent chemoradiotherapy (weekly cisplatin); other 285 patients received sequential chemoradiotherapy (paclitaxel and cisplatin). Acute adverse events, chronic radiation damage of rectum, and QoL were collected and analyed. The digestive tract symptoms and QoL were evaluated based on EORTC QLQ-C30 questionnaires at one week after surgery (M0), during adjuvant therapy period (M1), and at 12 months and 24 months after the completion of treatments (M12 and M24), respectively. Higher scores in the functional catalog and overall quality of life indicated better quality of life, while higher scores in the symptom catalog indicated severe symptoms and worse QoL. Chronic radiation rectal injury was defined as digestive symptoms that were not improved within three months after radiotherapy. Grading standard of acute adverse events and chronic radiation rectal injury was according to the gastrointestinal part of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE Version 4.0). The mean total radiation dosage of 848 patients was (47.8±4.6) Gy. During adjuvant therapy, the common symptoms of acute intestinal dysfunction were nausea (46.0%, 390/848), vomiting (33.8%, 287/848), constipation (16.3%, 138/848) and abdominal pain (10.3%, 87/848). At M12 and M24, the number of 0 QLQ-C30 questionnaires collected was 346 and 250, respectively. QLQ-C30 questionnaires showed that the scores of nausea or vomiting, appetite decrease, diarrhea, constipation, etc. were improved obviously at M12 or M24 compared with those at M0 or during M1 (all <0.05). As the extension of the follow-up time, the score of the overall QoL of patients gradually increased [M0: 59.7 (0.0-100.0); M1: 63.1 (0.0-100.0); M12: 75.2 (0.0-100.0); M24: 94.1 (20.0-120.0); H=253.800, <0.001]. Twelve months after the completion of treatments, the incidence of chronic radiation rectal injury was 9.8% (34/346), mainly presenting as abdominal pain, constipation, stool blood, diarrhea, mostly at level 1 to 2 toxicity (33/34, 97.1%). One patient (0.3%) developed frequent diarrhea (>8 times/d), which was level 3 toxicity. Twenty-four months after all treatments, the incidence of chronic radiation rectal injury was 9.6% (24/250), which was not decreased significantly compared to that in the previous period (χ(2)=0.008, =0.927). The symotoms of one patient with level 3 toxicity was not relieved. The common symptoms of patients with pelvic maligant tumors during postoperative adjuvant radiotherapy include nausea, vomiting, constipation, abdominal pain and diarrhea. These symptoms are alleviated obviously at 12 and 24 months after adjuvant radiotherapy, and the QoL is significantly improved. However, a few patients may develop chronic radiation rectal injury which is not improved for years or even decades, and deserves attention in clinical practice.