DEVELOPMENT OF AN ADAPTIVE RADIOTHERAPY PROTOCOL FOR CERVICAL CANCER PATIENTS IN MEDAN

Abstract

Cervical cancer continues to pose a significant global health burden, particularly in low- and middle-income countries, with approximately 604,000 new cases and 342,000 deaths reported in 2020 by the World Health Organization. Radiotherapy is a cornerstone of curative-intent treatment for this malignancy; however, conventional approaches often fail to adequately account for inherent anatomical changes, such as tumor shrinkage and organ motion, that occur throughout the treatment course. This variability can lead to suboptimal dose delivery to the target volume and increased toxicity to surrounding healthy tissues. Consequently, the development and implementation of adaptive radiotherapy (ART) protocols, which dynamically adjust treatment based on daily or weekly anatomical variations, are crucial for optimizing efficacy and minimizing morbidity. Despite the recognized benefits of ART, a critical research gap exists in the development and validation of tailored ART protocols for specific clinical settings, such as Medan, Indonesia, where access to advanced imaging and personalized treatment planning resources may be constrained. Addressing this gap is imperative to enhance treatment outcomes for cervical cancer patients in such regions. This study, therefore, aimed to develop and validate an adaptive radiotherapy protocol specifically for cervical cancer patients undergoing curative-intent treatment at a tertiary care hospital in Medan, Indonesia, guided by principles of image-guided radiotherapy (IGRT) and dose-painting strategies informed by local anatomical and dosimetric variations. We hypothesized that implementing this developed adaptive protocol would lead to significantly improved target volume coverage and reduced dose to organs at risk when compared to a standard, non-adaptive treatment approach. To achieve these objectives, a prospective observational study design was employed, chosen for its capacity to effectively capture real-world treatment variations. The study enrolled a cohort of 50 cervical cancer patients (Stage IB2-IVA) undergoing external beam radiotherapy, with consecutive enrollment upon diagnosis and consent. Daily cone-beam CT (CBCT) imaging was acquired for each patient, enabling volumetric assessment of the tumor and surrounding organs at risk throughout the treatment duration. Treatment plans were retrospectively analyzed, comparing initial plans with adapted plans generated based on weekly CBCT assessments, utilizing the Elekta Monaco treatment planning system for dosimetric evaluation. Key dosimetric parameters assessed included planning target volume (PTV) coverage (V95%) and dose to organs at risk (bladder, rectum, small bowel). Statistical analysis involved paired t-tests and Wilcoxon signed-rank tests to compare dosimetric outcomes between initial and adapted plans. Our findings revealed significant anatomical changes during radiotherapy, with an average PTV volume reduction of 15% by week 3. The developed adaptive protocol demonstrated a statistically significant improvement in PTV coverage, with the mean V95% increasing from 91.2% ± 3.5% in the initial plans to 96.8% ± 2.1% in the adapted plans (p < 0.001, Cohen's d = 1.8). Furthermore, significant reductions in dose to organs at risk were observed: the mean rectal dose decreased by 18% (p < 0.005), and the mean bladder dose decreased by 12% (p < 0.01). Notably, a subset of patients (n=10) who exhibited early and substantial tumor shrinkage experienced even greater dosimetric benefits from adaptation. In conclusion, the developed adaptive radiotherapy protocol effectively addressed anatomical variations during cervical cancer treatment in a Medan-based cohort, resulting in superior target coverage and reduced organ-at-risk toxicity. This study offers a practical and validated ART framework for resource-limited settings, contributing theoretically to the understanding of treatment adaptation in cervical cancer and practically by providing a pathway to improve patient outcomes. Future research is recommended to prospectively evaluate the impact of this protocol on local control and survival rates.