Sep 29

SS 41 - Optimizing Radiation Therapy in Gynecologic Cancers: Fractionation, Targeting, and Toxicity Reduction

324 - Hypofractionated IMRT and Weekly Cisplatin in Patients with Stage IIB and IIIB-C1 Cervix Cancer: A Phase I/II Study - The HYPOTHESIS Trial

03:55pm - 04:05pm ET

Room 162

Presenter(s)

Heloisa de Andrade Carvalho, MD, PhD - University of São Paulo, Sao Paulo, Sao Paulo

H. D. A. Carvalho¹, E. Santos², S. R. Stuart³, M. Perna⁴, J. J. Mansure⁵, J. Alfieri⁶, and L. Souhami⁴; ¹Hospital das Clinicas da Faculdade de Medicina - University of São Paulo, Brazil, Sao Paulo, Brazil, ²Liga Norte Riograndense Contra o Câncer, Natal, Rio Grande, Brazil, ³Instituto Brasileiro de Controle do Cancer, São Paulo, Brazil, ⁴McGill University Health Centre, Montreal, QC, Canada, ⁵McGill University Health Centre, Montreal-Ouest, QC, Canada, ⁶McGill University Health Center, Montreal, QC, Canada

Purpose/Objective(s):

Cervical cancer remains a serious public health problem worldwide and is the most frequent cause of cancer-related death among women in developing countries. Standard treatment for locally advanced cervix cancer consists of external beam radiotherapy (EBRT), combined with weekly cisplatin, conventionally delivered over 25 to 30 daily fractions. For patients from low- and middle-income countries, these daily visits may represent a significant financial burden. We report preliminary results of a prospective Phase1/2 study of hypofractionated EBRT plus high dose-rate brachytherapy (HDRB) with weekly cisplatin for patients (pts) with stage IIB and IIIB-C1 disease.

Materials/Methods:

Patients with histologically proven, newly diagnosed. cervical cancer, stage IIB or IIIB-C1 entered this study. All pts underwent full staging with blood test, abdominopelvic CT scan and pelvic MRI. Primary endpoints were feasibility and toxicity, pelvic control rate and patterns of failure. EBRT was delivered using IMRT/VMAT to a dose of 40.5 Gy in 15 fractions, given concomitantly with weekly cisplatin (40 mg/m²) followed by 24 Gy in 3 fractions of image-guided HDRB, delivered to the CTV-HR. We used Fleming’s one-sample multiple testing procedure to calculate a final sample size of 37 patients to detect a pelvic disease control rate of 60%.

Results: A total of 39 patients entered the study. Five patients were considered ineligible: 2 withdrew consent. 1 had para-aortic disease, and 2 had a concurrent malignancy. A total of 34 eligible patients, with a median age of 45 years (range: 27-90), were analyzed in January 2026: 19 stage IIB, 9 stage IIIB, and 6 stage IIIC1. At a median follow-up of 18 months (range: 6-35), 28 patients remain disease-free. Four patients died at 6- (2 patients), 7- and 9-months post therapy. Analysis of patterns of failure revealed that 4 patients failed only locally (stage IIB and IIIC1), 1 failed only distantly (stage IIIB) and 1 failed locally and distantly (stage IIIB) corresponding to a pelvic disease control rate of 85%. Only one patient (90-year-old) was unable to complete her EBRT due to grade 4 diarrhea. Except for one patient who had a grade 3 diarrhea, all others tolerated EBRT well with temporary = grade 2diarrhea. There has been no documented late toxicity. The 2-year overall survival probability is 82%.

Conclusion:

Our study shows that hypofractionated EBRT in locally advanced cervix cancer is feasible, relatively well tolerated and seems to provide adequate local disease control. Preliminary results are encouraging with valuable shortening of overall treatment time, offering advantages in healthcare resource utilization and patient convenience. Longer follow-up time is required to fully evaluate oncological outcomes.