A Pilot Study of Moderately Hypo-Fractionated Whole Pelvic Radiotherapy with Concurrent Chemotherapy and Image-Guided High Dose Rate Brachytherapy for Locally Advanced Cervical Carcinoma

Purpose/Objective(s)

The standard treatment of locally advanced cervical carcinoma (LACC) is whole pelvic radiotherapy (WPRT) with concurrent cisplatin and intracavitary brachytherapy (ICBT). EBRT is typically delivered to a dose of 45-50.4 Gray at 1.8-2 Gray per fraction. While moderate hypofractionation (H-EBRT) have been practiced, prospective evidence is limited. We evaluated the role of H-EBRT in terms of toxicities and clinical outcome in LACC.

Materials/Methods

50 patients of squamous cell carcinoma of cervix were recruited in this prospective interventional trial between December 2018-December 2021 (CTRI/2018/11/016415). Patients were treated with WPRT 40 Gray in 16 fractions over 3.5 weeks with boost to pelvic lymph nodes 10 Gray in 4 fractions with 3-DCRT and concurrent cisplatin weekly 40 mg/m² followed by image guided high dose rate ICBT 7Gray in 4 fractions. Cumulative EQD2 (equivalent dose at 2 Gray per fraction) for high-risk clinical target volume and organs at risk were derived. Acute and late toxicities were recorded as per CTCAE version 4.0 and RTOG criteria respectively. Disease free survival (DFS) and overall survival (OS) were estimated by Kaplan Meier method

Results

Patient characteristics are summarized in Table 1. All patients completed intended course of treatment. 6 patients received nodal boost. Median number of concurrent chemotherapy cycles were 4 (range 3-5). Median (range) cumulative EQD2 for HR-CTV, rectum, bladder and sigmoid were 80.15 (68-104.9), 65.91 (51.1-75.18), 82.05 (58.58-94.96) and 55.96 (46.5-86.76) respectively. Acute ≥ Grade 2 and ≥ Grade 3 gastrointestinal (GI), genitourinary (GU), anemia, leucopenia, and thrombocytopenia were seen in 20 (40%) and 10 (20%), 5 (10%) and 3 (6%), 10 (20%) and 3 (6%), 15 (30%), and 4 (8%), 6 (12%), and 3 (6%), respectively. Late grade 2 and grade 3 GI toxicity was seen in 6 (12%) and 2 (4%) patients and late grade 2 GU toxicity were observed in 3 (6%) patients. Three patients had developed recurrence at the time of last follow-up and all three died from disease. Estimated 2- and 3-year overall survival was 94.9% and 90.6% respectively and 2- and 3-year DFS was 92.7% and 92.7% respectively.

Conclusion

Moderately hypo-fractionated WPRT is well tolerated with acceptable acute and late toxicity profiles and yielded excellent clinical outcome. This schedule would lead to lesser overall treatment time, increased compliance and also be resource sparing and cost effective. Longer follow up would yield more data on late toxicity. Randomized study comparing this schedule with conventional fractionated schedule is warranted.