**7. Treatment‐related adverse events**

Late bladder, gastrointestinal, and vaginal toxicities have been reported by previous studies. In the Retro-EMBRACE study [17], five‐year Grade 3–5 toxicity in the bladder, gastrointestinal tract, and vagina among 610 patients affected 5, 7, and 5%, respectively. Ribeiro et al. also reported Grade 3–4 late rectal, urinary, sigmoid, and vaginal morbidity rates were 5, 6, 2, and 5%, respectively, in their long-term treatment outcome study [16]. They also identified a correlation between rectal D2cm3 > 65 Gy and Grade > 3 late morbidity. Among patients treated at Kobe University Hospital, Grade 3 rectal toxicity occurred in two (4%) patients. No Grade 3 or greater late bladder and vaginal toxicities have occurred to date.

Acute toxicities are rarely reported in published studies. According to our experience, hematological toxicity is the most frequent, especially in patients treated with concurrent chemoradiotherapy (CCRT). Among the 50 patients treated at Kobe University Hospital, Grade 3 or greater acute hematologic toxicity occurred in 36 (72%) patients. Procedure-related complications should also be reported. In the early period, mild pressure ulcers around the buttocks occurred in five patients. Respiratory suppression occurred in one patient who received intravenous sedation. In addition, interstitial needles may cause severe complications. The most common is bleeding. It is sometimes difficult to manage extravaginal bleeding caused by laceration of the vaginal wall. It is also important to be aware of possible intraabdominal bleeding. This may be caused by injury to the uterine arteries. Performing CT immediately after removal of the applicators may be useful for the early detection of intraabdominal bleeding.

In summary, according to the results from previous studies and our experience, Grade ≥3 late treatment-related toxicity occurs in approximately 5% of patients. Acute severe hematologic toxicity frequently occurs in patients treated with CCRT. The role of the CS technique performed for the protection of OAR from higher doses should be discussed from the aspect of toxicity. Monitoring is essential for procedure-related complications. Interstitial needles can cause severe complications. It is necessary to improve procedures, including needle implantation, to prevent complications.
