Dynamic γ-H2AX response in blood lymphocytes for prediction of radiotherapy induced bladder toxicity in cervical cancer patients

Sep 23, 2026

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Radiotherapy for advanced cervical cancer often causes unintended genitourinary toxicity, particularly bladder damage, yet predicting severe outcomes remains difficult. This prospective study evaluates γ-H2AX focus kinetics in peripheral blood lymphocytes as a surrogate DNA damage response measure. In 43 FIGO stage IIIB patients, γ-H2AX induction and decay after radiotherapy and CT are quantified by flow cytometry, with bladder toxicity graded by RTOG criteria. Persistent 24-hour foci correlate with higher toxicity risk.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

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Background and objectives

Methods

Results

Interpretation and conclusions

Keywords

Indian J Med Res 163, January 2026, pp 11-18 DOI: 10.25259/IJMR_ 1602_2025 Original Article Dynamic γ-H2AX response in blood lymphocytes for prediction of radiotherapy induced bladder toxicity in cervical cancer patients Geofrey John, 1,\# Shubham Ghanekar, 1,\# Donil Dominic,1 Jitendra Ramakant Gawde,2 Tapas Dora,1 Supriya Jayant Chopra,1 & Jayant S. Goda1 Departments of 1Radiation Oncology, and 2Statistics, Tata Memorial Centre, Homi Bhaba National Institute, Mumbai, Maharashtra, India Received June 21, 2025; Accepted October 27, 2025; Published February 28, 2026 Background and objectives: Radiotherapy for advanced cervical cancer (CaCx) often results in unintended genitourinary toxicities, notably bladder damage. Predicting such radiation-induced toxicity remains challenging. γ-H2AX, a marker of DNA double-strand breaks (DSBs), offers promise as a predictive biomarker for radiosensitivity. This study aimed to evaluate γ-H2AX foci kinetics in peripheral blood lymphocytes (PBLs) as a surrogate for DNA damage response and a predictor of bladder toxicity in CaCx patients undergoing pelvic radiotherapy. Methods: In this prospective study, 43 FIGO stage IIIB CaCx patients were enrolled. Stage I (n=31) assessed γ-H2AX induction post-CT simulation (2–6 mGy); Stage II (n=34) evaluated γ-H2AX kinetics across three radiotherapy fractions (FR1, FR13, FR25) during external beam radiotherapy (50 Gy in 25 fractions ± cisplatin). Blood samples were collected at baseline, 1-, 4-, and 24-h post-irradiation. γ-H2AX foci were quantified via flow cytometry. Bladder toxicity was graded usingRadiation Therapy Oncology Group (RTOG) criteria. Results: CT and radiotherapy both induced significant γ-H2AX foci, peaking at 1 h. Patients without bladder toxicity showed higher foci induction and faster decay (1→4h: 48.9% vs. 39.4%; 1→24h: 43.6% vs. 12.8%) across all fractions. Persistent foci at 24 h correlated with increased toxicity risk, indicating deficient DNA repair capacity. Interpretation and conclusions: γ-H2AX foci kinetics effectively reflect in vivo DNA repair efficiency and predict radiation-induced bladder toxicity. This minimally invasive biomarker may guide personalized radiotherapy, enabling early identification of high-risk patients and potential use of radioprotectors or treatment modifications. Keywords γ-H2AX; Bladder toxicity; Cancer cervix; Chemoradiotherapy; CT scan; Peripheral blood lymphocytes Concurrent chemoradiotherapy (CCRT) is the standard treatment for advanced cervical cancer (CaCx), improving survival but often causing significant toxicity to adjacent organs like the bladder, leading to genitourinary toxicity, including haematuria, incontinence, and pain, which can affect up to 80% of patients and compromise treatment adherence and quality of life.1–3 Despite advances in imaging and radiation planning, predicting which patients will experience severe toxicity remains difficult.4,5 Several clinical studies have examined γ-H2AX as a marker of normal tissue sensitivity to radiotherapy, mainly \#Equal contribution in breast, prostate, and head-and-neck cancers, often using single post-treatment time points or small patient 6–10 groups. Markers of individual radiosensitivity could allow treatment to be tailored, maximizing effectiveness while reducing side effects. The DNA damage response (DDR) plays a central role in determining cellular radiosensitivity. Inefficient repair of radiation-induced DNA double-strand breaks (DSBs) leads to persistent damage, inflammation, and long-term toxicity of theirradiated tissue. Individual differences in the DDR capacity may explain why patients receiving the How to cite this article: John G, Ghanekar S, Dominic D, Gawde JR, Dora T, Chopra SJ, et al. Dynamic γ-H2AX response in blood lymphocytes for prediction of radiotherapy induced bladder toxicity in cervical cancer patients. Indian J Med Res. 2026;163:11-18 . DOI: 10.25259/IJMR_ 1602_2025. © 2026 Indian

FAQs

What biomarker was evaluated to predict bladder toxicity?

The study evaluates γ-H2AX focus kinetics in peripheral blood lymphocytes as a surrogate for DNA damage response and radiosensitivity.

How were γ-H2AX foci measured and when were samples collected?

γ-H2AX foci were quantified by flow cytometry, using blood samples collected at baseline and 1, 4, and 24 hours after irradiation.

What relationship was observed between γ-H2AX persistence and bladder toxicity risk?

Patients without bladder toxicity showed higher foci induction and faster decay, while persistent foci at 24 hours correlated with increased toxicity risk, suggesting deficient DNA repair capacity.

Sep 23, 2026

Uploaded by Bintang