Intensity-modulated Radiation Therapy (IMRT) May Reduce Diarrhea With Similar Treatment Efficacy Even In Japanese Treatment Strategy For Cervical Cancers

Abstract

The RTOG 1203 trial showed that IMRT after hysterectomy could reduce acute radiation enteritis (ARE) compared to 3-dimensional conformal radiotherapy (3DCRT). However, it should be investigated whether IMRT could reduce ARE in radical radiotherapy for cervical cancers, considering the inter- and intra-fractional motions of the uterus (5-15 mm) and larger target volume. In Japan, treatment strategy for cervical cancers differs from that of other countries. The intestine is shielded during whole-pelvic irradiation (WPI) and brachytherapy starts earlier. Thus, even in 3DCRT, the ARE incidence can be lower than in other countries. We applied radical IMRT for cervical cancers using tomotherapy and investigated whether the IMRT protocol could reduce ARE and other toxicities. We reviewed patients with cervical cancers treated at 3 institutions that employed the same protocol. In the protocol, patients with UICC 8th stage IB-IVA cervical cancers received radical WPI ± paraaortic irradiation with 45-50.4 Gy delivered at a daily fraction of 1.8 Gy five times a week. Platinum-containing chemotherapy was delivered to ≥ stage III or tumors with ≥ 4 cm in the maximum diameter. After 20-30 Gy of WPI depending on the stage, the rectum, bladder and intestine were shielded and intracavitary brachytherapy (2-4 times at a point A dose of 5-6 Gy) was carried out. In IMRT, a block structure was contoured instead of the center shielding in 3DCRT. The block structure median dose was reduced to ≤ 0.9 Gy/fr. From 2007 to 2011, 3DCRT was used. From 2012, the IMRT protocol was introduced. We compared the IMRT and 3DCRT groups. All patients treated with the protocols were analyzed except patients with: 1) previous history of hysterectomy or radiotherapy and 2) small cell cancer. ARE was defined as the increase in stool of 4–6 times per day over the baseline. In total, 169 patients were treated according to the protocols. Of them, IMRT was delivered to 93 (median age, 63 years) and 3DCRT to 76 (61 years). Chemotherapy was administered to 73 in the IMRT group and 50 in the 3DCRT group (p = 0.08). Lymph node metastases were seen in 44 in the IMRT group and 26 in the 3DCRT group (p = 0.12). The 3-year overall survival and locoregional recurrence rates after IMRT were 84% and 17%, respectively. In the 3DCRT group, these rates were 70% and 20%, respectively. No difference was seen between the 2 groups (p > 0.2). ARE occurred less frequently in the IMRT group than in the 3DCRT group (17/93 vs 24/76, p < 0.05). Grade 3 toxicities were observed in 5 in the IMRT group (rectal bleeding 2, sigmoid colon stenosis 1, bladder tamponade 2) and in 3 in the 3DCRT group (rectal bleeding 1, small intestinal perforation 2) (p = 0.73). There was no ≥ grade 4 toxicity in both groups. Even in the Japanese treatment strategy for cervical cancers, use of IMRT may reduce ARE with similar treatment efficacy.