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Over the last decades, Brachytherapy (BT) with or without supplemental External Beam Radiotherapy (EBRT) has demonstrated excellent effectiveness in localized advanced pelvic cancers, especially in patients with prostate and cervical malignancies. In recent years, quality of life after BT has become a concerning issue among physicians and patients for selecting the optimal treatment modality. Although brachytherapy allows for rapid dose falloff, the rectal wall still receives high doses of radiation due to the proximity to the tumor. Literatures show 5-7% of the patients complain of grade II or higher rectal toxicities. Better knowledge of the dose-toxicity relationship is essential for safe dose escalation to minimize rectal toxicity without impairing therapeutic benefit. This study was aimed to abstract and evaluate the studies which have developed a prediction model for rectal toxicity after BT in patients with pelvic cancer.

To identify relevant studies since 1995, MEDLINE was searched on August 31, 2021 using the terms related to “pelvic cancer sites”, “rectal toxicity”, “prediction model”, and “brachytherapy”. Two independent reviewers screened the citations. The papers were excluded if only a subset of patients received BT, entering/removing predictors were not reported, or mixed outcomes were used as the primary endpoint. Risk of bias associated with methodological conduct was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST).

Forty-three prediction models featuring 117 distinct predictors (Figure 1) were published between 1998 and 2019. A total of 20 (47%) and 21 (49%) models were developed for prostate and cervical cancers, respectively. One study included elderly rectal cancer patients and one study developed a model for patients with different gynecological cancers. Rectal toxicity varied significantly between studies (3%-39% for prostate and 7%-47% for cervical cancers). Thirty-nine (91%) of the studies performed combined EBRT and BT and 11 (52%) studies included the gynecology cancer patients with the history of chemotherapy. Radiation Therapy Oncology Group (RTOG) and Common Terminology Criteria for Adverse Events (CTCAE) were used in 61% and 19% of the studies as the outcome measuring standard. Regression, support vector machine, and neural network were used in 40 (93%), 2 (5%), and 1 (2%) studies, respectively. Only five studies (12%) reported the area under the receiver operating characteristic curve (0.58-0.91). All studies were judged to be at high risk of bias mainly due to methods of analysis (Figure 2).

The currently available models appear to be of suboptimal quality and therefore caution should be considered for using these models in clinical practice. Future model development studies should adhere to methodological guidelines because unreliable models could misguide clinical decision making. The identified predictors in this study can be used as the potential predictors in future models.