International Journal Of Radiation Oncology, Biology, Physics[JOURNAL]
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200 papers
Memantine for Prevention of Cognitive Late Effects in Children and Adolescents Receiving Radiation Therapy for Brain Tumors: A Randomized, Controlled, Pilot Trial.
Conklin HM, Khan RB, Ashford JM … +7 more , Owens C, Simmons A, Bosley C, Hsu CW, Pan H, Gajjar A, Merchant TE
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42107784 · Full text
PURPOSE: Children receiving irradiation for brain tumors are at significant risk for cognitive deficits that notably impact quality of life. This is the first randomized, controlled investigation of the feasibility, acce...
PURPOSE: Children receiving irradiation for brain tumors are at significant risk for cognitive deficits that notably impact quality of life. This is the first randomized, controlled investigation of the feasibility, acceptability, and preliminary efficacy of memantine (an N-methyl-D-aspartate receptor antagonist) for reducing cognitive late effects in children and adolescents undergoing radiation therapy. METHODS AND MATERIALS: In a randomized, double-blind, controlled, pilot trial, children and adolescents took memantine (20 mg/d) or placebo for 12 weeks. Adherence was assessed using pill counts, and side effects were monitored using a structured interview. At baseline, 6 weeks (end of radiation therapy), 12 weeks (end of medication), and 1 year, participants completed cognitive assessments. RESULTS: Thirty patients (age, 11.93 ± 2.87 years; 47% male) were included; memantine (n = 16) and placebo (n = 14) groups did not differ in age, sex, race, socioeconomic status, or baseline intelligence quotient (P > .26). Study participation (71%) and medication adherence (88% completed 12 weeks; 97% of medication taken) were high. Side effects were minimal with no difference between memantine and placebo groups in increase in severity from baseline to any medication week (P > .23). At 12 weeks, effect sizes (ESs) indicate the memantine group had better processing speed (Cogstate Identification, ES = .61), academic fluency (Woodcock-Johnson IV Reading Fluency, ES = .45; Math Fluency, ES = .81), and fatigue (Pediatric Quality of Life Inventory [PedsQL] Multidimensional Fatigue Scale, ES = .72), with some benefits persisting 1 year post treatment (eg, Woodcock-Johnson IV Reading Fluency ES = .65; Math Fluency ES = .71). CONCLUSIONS: Study findings from this randomized, controlled trial indicate memantine used as a neuroprotectant during irradiation for children and adolescents with brain tumors is feasible and acceptable, with preliminary evidence for better cognitive outcomes that requires validation in a larger trial.
Deciphering Radiation-Induced Lung Injury: From Therapeutic Challenges to Macrophage-Centered Molecular Mechanisms and Innovative Interventions.
Yuan N, Zhao G, Zhang Q … +2 more , Cao J, Jiao Y
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42107783 · Publisher ↗
Radiation-induced lung injury (RILI) is a life-threatening complication of thoracic radiation therapy for malignancies. It poses 2 challenges in clinical management: the progression from acute radiation pneumonitis to ir...
Radiation-induced lung injury (RILI) is a life-threatening complication of thoracic radiation therapy for malignancies. It poses 2 challenges in clinical management: the progression from acute radiation pneumonitis to irreversible pulmonary fibrosis and the limitations of current therapies, such as glucocorticoids and antifibrotic drugs, because of efficacy constraints and adverse effects. Recent studies have revealed that pulmonary macrophages form a spatiotemporally regulated inflammatory-fibrotic coupling network through phenotypic switching. Specifically, alveolar macrophages exhibit M1 proinflammatory polarization during the acute phase, whereas interstitial macrophages transition to M2 profibrotic phenotypes in the chronic phase. This biphasic alveolar macrophages/interstitial macrophages regulatory mechanism provides critical insights for the selection of therapeutic targets. Using this information, drug delivery systems based on nanotechnology-with surface modifications for targeting and drug release-have the potential to change macrophages and related signals in the body, overcoming current treatment limits. This review methodically elucidates recent breakthroughs in radiation-induced lung injury molecular mechanisms and highlights advances in nanomedicine-driven cell-targeted therapies, to provide theoretical foundations for developing multimodal precision intervention strategies.
Optimizing Transmission FLASH Radiation Therapy for Large-Field Postmastectomy Breast Treatment.
Zafar AJ, Dutta SW, Case MJ … +5 more , Diamond Z, Bohannon D, Jagsi R, Yang X, Zhou J
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42107782 · Publisher ↗
PURPOSE: We investigated the effect of scanning speed, beam configuration, and dose-rate modeling on the FLASH effect in postmastectomy proton transmission beams planning and evaluated the potential of spot scanning path...
PURPOSE: We investigated the effect of scanning speed, beam configuration, and dose-rate modeling on the FLASH effect in postmastectomy proton transmission beams planning and evaluated the potential of spot scanning path optimization for enhancing the FLASH effect. METHODS AND MATERIALS: Five patients with left-sided postmastectomy breast cancer (32 Gy/5 fractions) were retrospectively replanned with single-energy (249 MeV) tangential transmission beams, supplemented by a clinical en face beam for dose homogenization. FLASH evaluation employed 2 models: Krieger's FLASH effectiveness model (FEM) and Folkerts' average dose-rate (ADR) framework. Plans were simulated under conventional pencil beam scanning, split-field, and optimized spot sequences (using genetic algorithm [GA]), with vertical scan speeds varied from 10 to 20 mm/ms. FLASH effect in normal tissues was quantified by the percentage of voxels meeting the threshold (≥4 Gy at ≥40 Gy/s). A dose adjustment factor of 0.67 was applied to voxels meeting FLASH criteria to compute FLASH-weighted dose metrics in normal tissues within the chest wall target, whereas the physical dose to tumor cells remained unchanged. RESULTS: The FLASH effect showed high sensitivity to scanning patterns and model selection. Increasing vertical scan speed from 10 to 20 mm/ms increased the FLASH in clinical target volume (CTV) by 22% (ADR) and 12% (FEM), whereas in skin, it rose from 41.4% to 58.8% (ADR) and 8.4% to 13.1% (FEM). Split-field delivery improved the temporal distance between the vertical columns of the spot scanning pattern, yielding a superior FLASH effect, which is up to a 9.2 Gy reduction in CTV (FLASH-corrected) D with the ADR model. GA-based optimization shortened scan time and provided FLASH comparable with split-field delivery, with a CTV D reduction of 7.87 Gy (ADR GA), with skin D reductions of 2 to 3 Gy. CONCLUSION: This study demonstrates that FLASH outcomes are highly sensitive to scanning trajectory, scan speed, and model selection. Beyond these parameters, optimizing spot delivery using a path minimizer, such as GA, can further improve the dose-rate distribution in healthy voxels across all scenarios.
Mature Outcomes of 61.2 Gy Concomitant Boost Thoracic Radiation Therapy in Limited-Stage Small Cell Lung Cancer: CALGB 30610 (Alliance)/RTOG 0538.
Bogart JA, Wang X, Masters G … +10 more , Komaki R, Gaspar LE, Heymach J, Dobelbower MC, Kuzma C, Waqar SN, Petty W, Stinchcombe TE, Bradley JD, Vokes E
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42086125 · Full text
PURPOSE: We report mature outcomes of patients with limited-stage small cell lung cancer randomly assigned to the 61.2 Gy concomitant boost (CB) thoracic radiation therapy (TRT) arm of Cancer and Leukemia Group B (CALGB)...
PURPOSE: We report mature outcomes of patients with limited-stage small cell lung cancer randomly assigned to the 61.2 Gy concomitant boost (CB) thoracic radiation therapy (TRT) arm of Cancer and Leukemia Group B (CALGB) 30610/Radiation Therapy Oncology Group (RTOG) 0538. The CB arm was discontinued after planned interim analysis; however, the study provides the largest prospective data set using 61.2 Gy CB TRT. METHODS AND MATERIALS: Eligible patients had limited-stage small cell lung cancer with regional lymph node involvement and Eastern Cooperative Oncology Group performance status 0 to 2. TRT began with either the first or second (of 4 total) cycle of cisplatin-based chemotherapy. Three-dimensional conformal radiation therapy or intensity modulated radiation therapy planning was required. In the initial phase of the trial, patients were randomly assigned with a 1:1:1 allocation to 45 Gy twice daily, 70 Gy once daily, and 61.2 Gy CB TRT. RESULTS: Ninety-three patients were assigned to receive 61.2 Gy CB TRT. After a median follow-up of 115 months for surviving patients, median overall survival and progression-free survival were 32.3 months (95% CI, 20.4-44.8 months) and 15.4 months (95% CI, 10.0-24.0 months), respectively. Five-year overall survival was 28.5% (95% CI, 20.6-39.6). Rates of grade 3 and 4 nonhematologic adverse events were 40.9% and 25%, including 16% dysphagia and 7% severe pulmonary toxicity. CONCLUSIONS: CB TRT outcomes appear similar to contemporaneous trials using 45 Gy twice-daily or high-dose once-daily TRT and compare favorably with prior phase 2 data. Improved outcomes highlight the impact of advances in staging and radiation therapy techniques, although additional factors may have contributed.
Palbociclib Enhances Radiation Therapy Efficacy by Promoting Apoptosis and Immune Modulation in Oral Squamous Cell Carcinoma.
Lee PY, Lee PH, Tu HF … +4 more , Liao TL, Chung YH, Chiang IT, Hsu FT
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42086124 · Publisher ↗
PURPOSE: Radiation therapy (RT) remains a cornerstone in the treatment of oral squamous cell carcinoma (OSCC), though its efficacy is often hindered by resistance mechanisms. Palbociclib, a selective cyclin-dependent kin...
PURPOSE: Radiation therapy (RT) remains a cornerstone in the treatment of oral squamous cell carcinoma (OSCC), though its efficacy is often hindered by resistance mechanisms. Palbociclib, a selective cyclin-dependent kinase 4/6 inhibitor, has shown potential not only in suppressing tumor growth but also in modulating immune responses. METHODS AND MATERIALS: We evaluated the therapeutic synergy of palbociclib combined with RT in OSCC using human squamous cell carcinoma of the oral tongue (SAS) and mouse oral squamous cell carcinoma cell lines (MOC1) and an orthotopic mouse oral cancer cell line-bearing mouse model. In vitro cytotoxicity and radiosensitization were assessed using MTT assay, colony formation, flow cytometry, and apoptotic marker analysis. In vivo efficacy and toxicity were evaluated through tumor growth monitoring, histopathology, and immunohistochemistry. Immune profiling was conducted using flow cytometry and immunohistochemistry to examine innate and adaptive immune responses and immunosuppressive components. RESULTS: Palbociclib significantly enhanced RT-induced cytotoxicity, promoted G1 arrest, and activated both extrinsic and intrinsic apoptotic pathways. In vivo, the combination treatment inhibited tumor growth more effectively than either monotherapy without inducing systemic toxicity. Immune profiling revealed increased infiltration and activation of M1 macrophages, natural killer cells, cytotoxic T cells, and effector memory T cells. Concurrently, palbociclib mitigated RT-induced immunosuppression by reducing M2 macrophages, myeloid-derived suppressor cells, regulatory T cells, and programmed death-ligand 1 expression in tumor and lymphoid tissues. CONCLUSIONS: Palbociclib not only potentiates the direct antitumor effects of RT but also modulates the tumor immune microenvironment, enhancing immunogenicity and reducing suppressive pathways. These findings support the potential of palbociclib as a radiosensitizer and immunomodulatory agent in OSCC treatment.
Outcomes of 5- Versus 10-Fraction Radiation Therapy for Hepatocellular Carcinoma at a Veteran Affairs Hospital.
Qazi JJ, Kumar A, Godfrey D … +4 more , Palta M, Salama JK, Eyler CE, Boyer MJ
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42069261 · Publisher ↗
PURPOSE: To compare outcomes, liver toxicity, and survival between patients with hepatocellular carcinoma treated with hypofractionaed image-guided radiation therapy (HIGRT) delivered in 5 versus 10 fractions within a Ve...
PURPOSE: To compare outcomes, liver toxicity, and survival between patients with hepatocellular carcinoma treated with hypofractionaed image-guided radiation therapy (HIGRT) delivered in 5 versus 10 fractions within a Veterans Affairs (VA) population. METHODS AND MATERIALS: A retrospective review was performed of patients with unresectable or medically inoperable hepatocellular carcinoma treated with HIGRT at the Durham VA Medical Center between 2013 and 2024. Patients treated with palliative intent or lacking follow-up were excluded. The standard regimen was 50 Gy in 5 fractions; 50 Gy in 10 fractions was used when organ-at-risk constraints precluded 5-fraction delivery. Demographic, clinical, and dosimetric data were extracted from the VA National Corporate Data Warehouse. Outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Among 147 patients (median age, 67 years), 96 received 50 Gy in 5 fractions and 51 received 50 Gy in 10 fractions. Most patients had cirrhosis (93.9%) and Child-Pugh class A liver function (82.3%). Tumors were larger in the 10-fraction cohort (median, 35 cm vs 14 cm; P < .001). Treatment was well tolerated, with only 1 grade 3 event and no grade ≥4 toxicity. The cumulative grade ≥2 toxicity was similar between regimens (hazard ratio, 1.59; P = .25). Worsening of Child-Pugh score by ≥2 points occurred more frequently with 10 fractions (hazard ratio 2.15; P < .01), but this was associated only with higher mean liver dose in a multivariate model. Two-year local control was 90.7% for 5 fractions and 82.4% for 10 fractions; this difference was not significant after adjusting for tumor size. Median overall survival was 2.8 years, shorter in the 10-fraction cohort due to poorer baseline characteristics. CONCLUSIONS: Both 50 Gy in 5 and 10 fractions achieved excellent local control and minimal toxicity. The 10-fraction regimen is a safe, effective alternative when normal tissue constraints preclude 5-fraction HIGRT.
Glycoprotein Nonmetastatic B⁺ Myeloid-Derived Suppressor Cells Mediate Radiation-Induced Immune Suppression in Prostate Cancer and Are Targetable to Improve Systemic Control.
Mulvaney O, Chung JS, Kobayashi M … +6 more , Somatilaka BG, Pop LM, Zhang F, Cruz PD, Ariizumi K, Hannan R
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42069260 · Publisher ↗
PURPOSE: Stereotactic body radiation therapy (SBRT) provides excellent local control for localized prostate cancer (PC); however, systemic relapse remains the primary cause of death in high-risk patients, underscoring th...
PURPOSE: Stereotactic body radiation therapy (SBRT) provides excellent local control for localized prostate cancer (PC); however, systemic relapse remains the primary cause of death in high-risk patients, underscoring the need to understand and therapeutically address radiation-induced immune suppression. Here, we identify a previously unrecognized myeloid checkpoint pathway driven by glycoprotein nonmetastatic B (GPNMB⁺) myeloid-derived suppressor cells (MDSCs) as a dominant systemic response to clinical SBRT and demonstrate a tractable strategy to counter it. METHODS AND MATERIALS: We used paired peripheral blood samples from patients treated with SBRT to measure systemic MDSCs by flow cytometry, followed by ex vivo functional assays with patients' peripheral blood mononuclear cells. For further characterization, we used a syngeneic PC RM-9 tumor model. quantitative polymerase chain reaction and luciferase assays determined the mechanism observed. RESULTS: We observed a selective and reproducible expansion of GPNMB⁺ MDSCs accompanied by enhanced T-cell suppression. GPNMB blockade in patients' peripheral blood mononuclear cells rapidly and consistently restored T-cell activity, directly supporting the clinical feasibility of targeting this pathway. Likewise, in tumor-bearing mice, radiation upregulated GPNMB on MDSCs and its ligand syndecan-4 on tumor-infiltrating T cells. Therapeutically, combining anti-GPNMB antibody with radiation significantly improved local tumor control and reduced metastatic burden compared with radiation alone and outperformed programmed death-ligand 1 blockade. Transcriptomic and mechanistic analyses identified melanocyte-inducing transcription factor as a key regulator of radiation-induced GPNMB expression. CONCLUSIONS: Together, these findings define an actionable radiation therapy→ MDSC → GPNMB myeloid checkpoint that suppresses T-cell immunity in PC and demonstrate that targeting this pathway reverses radiation-induced immune suppression across human and murine systems. This work establishes a strong translational rationale for integrating MDSC-targeted therapy with SBRT to improve systemic control in localized high-risk PC.
Use of Hypofractionation Among Underserved Populations Undergoing Radiation Therapy for Cancer: Implications for Policy.
Murray NZ, Sokeye J, Horns JJ … +4 more , Chipman J, Gill H, Johnson S, O'Neil B
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42061522 · Publisher ↗
PURPOSE: To examine the use of hypofractionation among underserved populations, with a focus on implications for policy. METHODS AND MATERIALS: Using a 20% Medicare claims sample, we evaluated the receipt of hypofraction...
PURPOSE: To examine the use of hypofractionation among underserved populations, with a focus on implications for policy. METHODS AND MATERIALS: Using a 20% Medicare claims sample, we evaluated the receipt of hypofractionation, a short-course radiation therapy approach, among underserved versus nonunderserved populations. Hypofractionation was defined based on cancer/site-specific guidelines and expert review. Underserved groups included racially/ethnically minoritized, rural, and patients with low socioeconomic status. We included 4 cancer types that represent the majority of new cancer diagnoses and for which there is the highest level of support for hypofractionation. These included breast, colorectal, lung, and prostate cancer. Log-binomial regression models were used to assess the association between underserved status and hypofractionation use, adjusting for patient-level, practice-level, and area-level characteristics. RESULTS: We analyzed 6437 patients and found that 2200 were classified as underserved and 4237 as not underserved. Overall, 52.5% of patients received hypofractionation, and underserved populations were treated at similar rates to their nonunderserved counterparts. We noted a few exceptions. Rural patients with prostate cancer had a lower likelihood of receiving hypofractionation (relative risk, 0.59; P = .005), whereas rural patients with lung cancer had a higher likelihood of receiving hypofractionation (relative risk, 1.14; P = .039). CONCLUSIONS: Hypofractionation was received at similar rates among underserved and nonunderserved populations. Given existing disparities experienced by underserved patients with cancer, greater use of hypofractionation may contribute to more equitable outcomes. Implementation of policies that facilitate-rather than discourage-the use of hypofractionation, may reduce disparities experienced by underserved patients with cancer.
Temporal analysis of prostate Magnetic Resonance Linac data.
Koopmans PJ, Monshouwer R, Findhammer J … +3 more , Smeenk RJ, Verheij M, van der Bijl E
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42061521 · Publisher ↗
PURPOSE: There is a strong desire to exploit daily magnetic resonance_linac (MRL) imaging for biomarker extraction and outcome prediction. Current prediction models are based on pretreatment and follow-up scans. If MRL d...
PURPOSE: There is a strong desire to exploit daily magnetic resonance_linac (MRL) imaging for biomarker extraction and outcome prediction. Current prediction models are based on pretreatment and follow-up scans. If MRL data are to provide additional value, this would need to originate from the dynamic nature of MRL intratreatment signals. Demonstrating the existence of such dynamics and how to discover them is the purpose of this work. METHODS AND MATERIALS: We analyzed T-weighted (Tw) and diffusion MRL data of prostate cancer patients undergoing hypofractionated radiation treatment. Next to standard mask-based analyses, we introduce exploratory analyses using classic functional magnetic resonance imaging (fMRI) neuroimaging techniques, designed to determine both the existence and spatial location of temporal signal changes. Finally, we link dose deposition to the slope of observed Tw signal changes in pelvic bone tissue, chosen for its wide range of dose values received (0-26 Gy; 0-47 Gy EQD2). RESULTS: Mask-based analyses of the magnetic resonance imaging data of all fractions reveal Tw signal decreases for prostate tissue, whereas the gross tumor volume signal stays more constant throughout the treatment. The diffusion coefficient of the prostate gland remains constant, whereas the gross tumor volume shows an increase. Prostate volume increases by 10% in the first week, after which it slowly decreases again. The fMRI-inspired analysis shows prostate Tw signal change to be confined to the peripheral zone. Furthermore, it revealed signal changes in the rectum, bladder, pelvic and femoral bones, the zona orbicularis, and the penis (despite the latter only accumulating 3 Gy). The dose-effect relationship of pelvic bone shows a clear discontinuity with a sharp transition from 0% to 1.5% signal change per fraction within a very short dose interval between 0 and 1 Gy (0.55 Gy EQD2). CONCLUSIONS: Exploratory fMRI-inspired analyses were able to demonstrate many temporal, nonlinear trends in MRL data. This is promising for future biomarker research once MRL outcome data become more prevalent. The pelvic bone response shows signs of dose-threshold behavior with a sudden dose-response starting at 1 Gy.
One Year After a Cyberattack: Lessons Learned and Dosimetric Analysis of Contingency Radiotherapy Plans.
Cases C, Latorre-Musoll A, Candela-Juan C … +8 more , Valduvieco I, Antelo G, Moreno-López S, Herreros A, Serrano-Rueda S, Navarro-Palomas P, Saez J, Mollà M
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42043360 · Publisher ↗
PURPOSE: Cyberattacks on health care institutions pose significant risks to patient care, particularly in radiotherapy departments, which are heavily reliant on digital systems. This study examines the impact of a ransom...
PURPOSE: Cyberattacks on health care institutions pose significant risks to patient care, particularly in radiotherapy departments, which are heavily reliant on digital systems. This study examines the impact of a ransomware attack on our hospital and evaluates the effectiveness of the contingency measures implemented to resume radiotherapy treatments. METHODS AND MATERIALS: Following the cyberattack, our radiotherapy department faced a complete shutdown. After an initial estimate considering a shutdown of several weeks, a contingency plan was executed, including manual patient data retrieval and collaboration with a backup hospital. Contingency plans were prepared and delivered within hours, despite a partial lack of information. These plans allowed some patients to restart treatment 3 days after the attack. A dosimetric analysis was performed for the contingency plans, including various pathologies, mainly glioblastoma, head and neck cancers, and lung cancer. We compared the original and contingency plans in terms of dose coverage to the clinical target volume, biological effective dose, and their clinical impact as assessed at the 1‑year follow‑up after the cyberattack. RESULTS: Treatments resumed within 12 days at our hospital. Patients with glioblastoma showed good target coverage because of generous margins, resulting in favorable outcomes. In head and neck cases, the lack of detailed imaging led to significant target volume misses, suggesting that more conservative initial treatments could have been beneficial. Lung cases demonstrated accurate peripheral lesion targeting but faced challenges in central lesions because of the absence of positron emission tomography information. In most cases, the approach of using a contingency plan, even with limited information, led to a higher biological effective dose than would have been achieved if treatment had been stopped until full recovery at our hospital. CONCLUSIONS: The study highlights the critical importance of robust contingency planning in radiotherapy departments, emphasizing the need for backup systems and tailored approaches based on tumor location and available diagnostic information. These lessons emphasize that preparedness for digital disruptions should not focus exclusively on information and technology infrastructure.
Outcomes of Stage IVA Cervical Cancer Treated with Radiation Therapy: A Systematic Review and Meta-Analysis.
Saini SK, Srivastava S, Goel A … +1 more , Sharma DN
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42034194 · Publisher ↗
FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We perfo...
FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We performed a systematic review and meta-analysis to evaluate survival outcomes, treatment-related morbidity, and prognostic factors in patients with stage IVA cervical cancer treated with definitive radiotherapy. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42024602426), PubMed, Embase, and Web of Science were searched through February 2025. Eleven studies comprising 492 patients met eligibility criteria. Pooled random-effects analyses demonstrated 2-, 3-, and 5-year disease-free survival rates of 41.5% (95% CI, 28.1-55.0), 34.2% (95% CI, 21.1-47.3), and 30.9% (95% CI, 16.0-45.8), respectively. Corresponding overall survival rates were 56.0% (95% CI, 46.2-65.9), 45.9% (95% CI, 35.9-55.9), and 34.8% (95% CI, 26.4-43.3). Weighted median disease-free survival and overall survival were 15.6 and 33.6 months, respectively. The pooled incidence of vesicovaginal or rectovaginal fistula was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 below 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy were consistently associated with improved outcomes. Despite curative-intent treatment, long-term survival remains poor and treatment-related morbidity substantial. Durable pelvic control remains the principal therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy appears essential for optimal outcomes, while future stage IVA-specific studies incorporating image-guided adaptive brachytherapy, advanced radiotherapy techniques, and systemic treatment intensification are needed to improve survival and reduce treatment-related morbidity.
Aly as a Key Regulator of DNA Repair and Immune Evasion in Esophageal Squamous Cell Carcinoma Radioresistance.
Ding S, Liang H, Wang J … +8 more , Zhu H, Li X, Zong Q, Ma X, Lu X, Sun Z, Li W, Luo J
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42034193 · Publisher ↗
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is frequently refractory to radiation therapy, in part because of inefficient DNA damage repair and an immunosuppressive tumor microenvironment. We investigated whether...
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is frequently refractory to radiation therapy, in part because of inefficient DNA damage repair and an immunosuppressive tumor microenvironment. We investigated whether ALYREF (Aly) coordinates radioresistance and immune evasion in ESCC. METHODS AND MATERIALS: Aly expression and its clinical associations were analyzed in the Cancer Genome Atlas (TCGA) cohorts and validated by immunohistochemistry in an independent ESCC cohort. Aly was genetically silenced or overexpressed in ESCC cell lines, followed by irradiation and subsequent assessment of clonogenic survival, reactive oxygen species (ROS) production, and apoptosis. Multi-omics analyses and mechanistic studies (protein interaction modeling, immunofluorescence, and DNA damage readouts) were performed to define pathways linking Aly to radioresponse and immune contexture. RESULTS: Aly was overexpressed in ESCC and associated with adverse clinical outcomes. Aly depletion suppressed ESCC growth and enhanced radiosensitivity, characterized by increased radiation-induced reactive oxygen species and apoptosis, as well as reduced clonogenic survival. Aly's loss was accompanied by changes consistent with impaired resolution of DNA double-strand break repair and activation of inflammatory signaling. Mechanistically, Aly engaged REV7-associated nuclear programs and Hsp70-linked cytoprotective signaling, thereby supporting DNA damage tolerance and survival after irradiation, and was correlated with an immunosuppressive contexture. CONCLUSIONS: Aly functions as a dual regulator of ESCC radioresistance by integrating DNA repair capacity and immune suppression. Targeting Aly may represent a strategy to radiosensitize ESCC and potentially improve responses to combined radiation therapy-immunotherapy.
Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.
Wisdom AJ, Temple H, Cui Y … +5 more , Del Vecchio CT, Kim T, White FM, Floyd SR, Spranger S
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42031225 · Full text
Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite aggressive multimodal therapy, including maximal safe resection, radiation therapy, and temozolomide chemotherapy, median...
Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite aggressive multimodal therapy, including maximal safe resection, radiation therapy, and temozolomide chemotherapy, median survival remains approximately 16 months, and nearly all tumors recur. Over the past 2 decades, numerous therapies that demonstrated promise in preclinical studies have failed to improve outcomes in randomized clinical trials, underscoring the therapeutic resistance that defines this disease. This resistance arises from the convergence of tumor-intrinsic mechanisms, microenvironmental constraints, and limitations of current preclinical models. In this review, we synthesize advances in understanding the molecular, cellular, and anatomic determinants of resistance to radiation therapy, chemotherapy, targeted therapies, and immunotherapies in adult GBM. We highlight how extensive intra- and intertumoral heterogeneity, transcriptional plasticity, and adaptive reprogramming enable tumor cells to evade cytotoxic stress. Key resistance mechanisms include activation of DNA damage response pathways, exploitation of hypoxic niches, therapy-induced mesenchymal transitions, and evasion of immune surveillance through impaired antigen presentation and a profoundly immunosuppressive tumor microenvironment. We further discuss how GBM exploits the unique immunologic features of the central nervous system, including the blood-brain barrier, limited antigen burden, and tolerogenic myeloid populations, to blunt the efficacy of immunotherapies. A major focus of this review is the role of preclinical models in shaping our understanding of therapeutic resistance. We critically evaluate established cell lines, patient-derived xenografts, syngeneic models, and genetically engineered mouse models, emphasizing both their strengths and their inability to fully recapitulate defining features of human GBM. Finally, we outline emerging strategies to overcome resistance, including rational combination therapies, adaptive trial designs, improved biomarker-driven stratification, and integrative modeling approaches. Together, these insights provide a framework for translating mechanistic understanding into more effective, durable therapies for glioblastoma.
Three-Dimensional Radiation Therapy Target Volume Definitions for Osteoarthritis-Consensus Statement of the International Benign Target Volume Group.
Steike DR, Seegenschmiedt MH, Shaffer R … +18 more , Weissmann T, Kriz J, Pascher F, Thole AM, Linke F, Wimmer C, Colin G, Montero A, Álvarez Rodríguez B, Hernanz de Lucas R, Sotoca A, Gomez Ordonez S, Cellini F, Reinartz G, Barron D, Koneru BN, Trombetta M, Eich HT
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42031224 · Publisher ↗
PURPOSE: Low-dose radiation therapy (LDRT) is a minimally invasive treatment option for pain management in selected patients with osteoarthritis (OA). However, standardized and internationally accepted target volume defi...
PURPOSE: Low-dose radiation therapy (LDRT) is a minimally invasive treatment option for pain management in selected patients with osteoarthritis (OA). However, standardized and internationally accepted target volume definitions are still lacking. METHODS AND MATERIALS: An international expert consortium of 15 institutions from Europe and the United States conducted a Delphi consensus process to define joint-specific target volumes based on the 3-dimensional (3D) concept of the clinical target volume (CTV). A standardized computed tomography data set ("homunculus") was used by all participants to ensure uniform anatomical reference for target volume delineation. RESULTS: Target volume definition includes inflammatory and OA-specific pathological features such as joint effusion, cysts, and subchondral sclerosis. The CTV encompasses the joint capsule and varies in its cranio-caudal extent among individual patients. Using joint-specific isocenter definitions-such as the midpoint between the femoral condyles for the knee joint-the 3D boundaries of the CTV can be determined. This approach enables anatomically precise delineation of the target volume, ensuring inclusion of inflammation-relevant structures while excluding uninvolved bone and soft tissue. CONCLUSIONS: This international consensus statement provides practical guidance for a standardized 3D target volume definition in the radiation therapy of OA. Accurate knowledge of joint anatomy and pathology, combined with precise target volume delineation and careful consideration of the clinical context, such as symptom distribution and the pattern of joint involvement, may support more consistent LDRT treatment planning for OA. These target volume definitions also provide a structured basis for future clinical studies and further clinical validation.
Deep Learning Blood Dosimetry Predicts Severe Lymphopenia and Survival After Craniospinal Irradiation.
Kim N, Seo SH, Chang JS … +6 more , Moon SG, Kang S, Park SY, Lim DH, Shin J, Kim JS
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42031223 · Publisher ↗
PURPOSE: Craniospinal irradiation (CSI) is a standard treatment for pediatric brain tumors and is increasingly used for leptomeningeal metastases. Although effective, CSI often causes radiation-induced severe lymphopenia...
PURPOSE: Craniospinal irradiation (CSI) is a standard treatment for pediatric brain tumors and is increasingly used for leptomeningeal metastases. Although effective, CSI often causes radiation-induced severe lymphopenia (RISL), which is associated with poor outcomes across various cancer types. We developed and validated a novel platform for personalized dosimetry of circulating blood cells (CBCs) and assessed its predictive value for RISL. METHODS AND MATERIALS: We combined a prospective pediatric CSI registry (initiated April 2018; n = 48) and retrospectively collected patients (January 2010-November 2024; n = 168). RISL was defined as grade 4 lymphopenia (<200/µL) during or within 1 week after CSI. The platform integrated deep learning-based whole-body segmentation, individualized blood volume modeling (HEDOS), patient-specific hemodynamics (cardiac output), and treatment delivery parameters to estimate CBC dose-volume histograms, which quantify the cumulative radiation dose distribution to circulating blood during CSI. CBC dose metrics were analyzed using LASSO, Random Forest, and XGBoost models, with and without cross-validation and Synthetic Minority Over-sampling Technique, to identify RISL predictors. RESULTS: Among 216 patients (median age 12 years; range, 2-68), proton beam therapy was used in 163 (75.5%). RISL occurred in 92 patients (42.6%). Among various CBC dosimetric parameters, CBC D5% consistently emerged as the most important predictor of RISL across all machine learning models. Stratification by CBC D5% with 3.0 GyE effectively differentiated overall survival and event-free survival outcomes (all P < .05). CONCLUSIONS: The current deep learning-based personalized blood dosimetry platform enables personalized CBC dosimetry during CSI. CBC D5% is associated with the development of RISL and survival outcomes. Personalized blood dosimetry may serve as a potential tool to identify patients at high risk for RISL, which may inform future efforts to optimize CSI planning.
FLASH Radiotherapy Mitigates Radiation-Induced Lymphopenia and Prevents Immunosuppression via Chk1-STAT3 Axis Modulation in a Preclinical Thoracic Irradiation Model.
Tao RH, Liu K, Aguilar E … +9 more , Wang M, Aggarwal S, Neill D, Velasquez B, Beddar S, Koong AC, Mohan R, Schüler E, Lin SH
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42031222 · Publisher ↗
PURPOSE: Radiation-induced lymphopenia is a frequent side effect of conventional radiation therapy (CONV RT), due to the high radiosensitivity of circulating lymphocytes. Ultra-high dose rate "FLASH" RT may preferentiall...
PURPOSE: Radiation-induced lymphopenia is a frequent side effect of conventional radiation therapy (CONV RT), due to the high radiosensitivity of circulating lymphocytes. Ultra-high dose rate "FLASH" RT may preferentially spare normal tissue while maintaining tumor control. This study evaluates the impact of single-fraction and multifraction thoracic FLASH RT on lymphocyte preservation, apoptosis, and immunosuppressive signaling in mice. METHODS AND MATERIALS: We compared the immunological impact of thoracic FLASH RT and CONV RT in C57BL/6 mice using single-fraction (17 Gy) and multifraction (2 Gy × 5) regimens using the Mobetron (IntraOp). Longitudinal blood sampling was performed at multiple time points postirradiation through facial vein bleed with flow cytometry analysis for CD4+, CD8+, CD19+, and NK cells to assess lymphocyte counts, apoptotic lymphocytes through Annexin V staining, and immune suppression by examining regulatory T cells and PD-1/PD-L1 expression. Mechanistic studies included immunofluorescence and Western blot analyses of splenic tissues to evaluate Chk1 and STAT3 signaling pathways. RESULTS: In single-fraction RT, FLASH significantly reduced lung and heart fibrosis (P <.0001) at 28 weeks post-RT. The FLASH effect was also seen acutely on circulating immune cells, with significantly reduced lymphocyte apoptosis and accelerated recovery of CD4⁺, CD8⁺, CD3⁺, NK, and B cell populations compared to CONV RT in both single-fraction and multifraction regimens. Conversely, CONV RT induced long-lasting increases in regulatory T cells and sustained PD-1 and PD-L1 expression on T- and B-cells at 2- and 5-months postirradiation in both fractionation regimens. Within the spleen, we also found CONV RT induced sustained activation of the Chk1-STAT3 pathway in CD45+ immune cells, which correlates with increased PD-1/PD-L1 expression. CONCLUSIONS: FLASH RT mitigates radiation-induced lymphopenia, reduces lymphocyte apoptosis, and prevents long-term immunosuppression by reduced activation of the Chk1-STAT3 pathway. These findings suggest FLASH RT may confer immunological advantages over CONV RT to enhance therapeutic efficacy.
Consolidative Camrelizumab Following Definitive Concurrent Chemoradiation Therapy With Involved-Field Irradiation in Locally Advanced Esophageal Squamous Cell Carcinoma: A Single-Arm Phase 2 Trial.
Cheng Y, Wang J, Lv X … +9 more , Liu Q, Wu Y, Liu Y, Zhao L, Pang Q, Zhao S, Cao F, Jiao W, Wang J
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42031221 · Publisher ↗
PURPOSE: Definitive concurrent chemoradiation therapy (dCCRT) is considered the standard treatment for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). However, approximately half of the patients...
PURPOSE: Definitive concurrent chemoradiation therapy (dCCRT) is considered the standard treatment for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). However, approximately half of the patients still experience local recurrence or distant metastasis. The CheckMate 577 trial, a phase III randomized clinical trial evaluating adjuvant nivolumab after neoadjuvant chemoradiotherapy and surgery, demonstrated that adjuvant nivolumab significantly improves disease-free survival in patients with resected esophageal or gastroesophageal junction cancer after neoadjuvant chemoradiation therapy. However, the role of consolidation immunotherapy in locally advanced unresectable esophageal cancer remains unclear. Camrelizumab, an anti-programmed death receptor 1 antibody, has shown antitumor activity in advanced or metastatic ESCC. We conducted a clinical trial to evaluate the efficacy of camrelizumab consolidation therapy in patients with unresectable, locally advanced ESCC following dCCRT. METHODS AND MATERIALS: This single-arm, phase 2 trial was conducted at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Eligible patients were aged 18 to 75 years with histopathologically confirmed, locally advanced (T1bN+M0, T2-4N0-2M0, or supraclavicular lymph node metastasis) unresectable or medically inoperable ESCC, who had not experienced disease progression after completing dCCRT. Patients received camrelizumab consolidation therapy (200 mg intravenously, day 1, every 2 weeks) for 12 months. After 12 months, patients could independently choose to continue immunotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included disease control rate, objective response rate, duration of response, overall survival (OS), and safety. RESULTS: Between April 2020 and November 2023, 43 patients were screened, 35 were enrolled, and 32 were included in the analysis. As of the data cutoff date (July 25, 2025), 12 patients had experienced disease progression, and 10 patients had died. The disease control rate was 59.4% (19 of 32). Neither the median PFS nor the median OS was reached. The 1-year, 2-year, and 3-year PFS rates were 81.3%, 62.5%, and 62.5%, respectively. The 1-year, 2-year, and 3-year OS rates were 96.9%, 77.7%, and 63.0%, respectively. Regarding safety, most adverse events (AEs) were grade 1 or 2. The most common AEs were anemia (68.8%), leukopenia (50.0%), and reactive cutaneous capillary endothelial proliferation (43.8%). Grade 3 AEs included leukopenia (12.5%) and thrombocytopenia (3.1%). No treatment-related deaths occurred. The incidence of pneumonitis in the cohort was 31.3%; all cases were grade 1 or 2, with no grade ≥3 pneumonitis observed. CONCLUSIONS: Consolidation camrelizumab following dCCRT with involved-field irradiation demonstrates promising efficacy and manageable toxicity in patients with unresectable locally advanced ESCC.
Development and Application of a Simplified Mathematical Model for the Estimation of Tumor Dose of Non-Small Cell Lung Cancer in BNCT.
Kao CF, Sheu RJ, Peir JJ … +5 more , Wu YH, Chen YW, Hu YW, Jen WC, Lee JC
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42025810 · Publisher ↗
PURPOSE: Lung cancer has exhibited a sustained increase in both incidence and mortality rates in recent years. This study aimed to develop and apply a simplified mathematical model for estimating tumor dose in boron neut...
PURPOSE: Lung cancer has exhibited a sustained increase in both incidence and mortality rates in recent years. This study aimed to develop and apply a simplified mathematical model for estimating tumor dose in boron neutron capture therapy for non-small cell lung cancer, to facilitate clinical treatment planning. METHODS AND MATERIALS: We analyzed the effects of 6 key parameters on dose distribution based on experimental data and established a simplified mathematical model to estimate tumor dose. The model was validated in selected patients with lung cancer under both fixed and random irradiation conditions. Patients were categorized according to whether dose limits of critical organs were exceeded, and the model's accuracy was further assessed in these subgroups. In addition, the surface-to-tumor center distance was defined to evaluate its correlation with the minimum prescribed dose for a single SBRT fraction. The study also investigated the effects of respiratory motion and setup errors on dose accuracy. RESULTS: The simplified mathematical model achieved estimated dose errors of 4.0% ± 2.8% under fixed irradiation and 4.4% ± 3.2% under random irradiation. For patients categorized based on critical organ dose limits, estimated errors were 9.3% ± 12.2% and 4.6% ± 9.8%, respectively. These results demonstrated the model's high accuracy. Analysis of surface-to-tumor center distance values revealed that 6.66 cm may serve as a threshold for patient selection to ensure the minimum prescribed dose. Respiratory motion introduced a dose estimation error within ±10%, and each 5-mm setup error caused <1% deviation, indicating that these effects are negligible. CONCLUSIONS: The proposed simplified mathematical model offered accurate and efficient tumor dose estimation for patients with non-small cell lung cancer undergoing boron neutron capture therapy. It served as a valuable reference in clinical practice, enabling physicians to rapidly assess tumor dose using medical imaging data, thus improving the efficiency and precision of treatment planning.
Does Pencil Beam Scanning Proton Therapy Impart a Higher Risk of Capsular Contracture Compared With Intensity Modulated Photon Radiation Therapy in the Postmastectomy Reconstruction Setting?
Zerey MM, Gal O, Feenstra NA … +7 more , Fagundes M, Rodrigues MM, Medina MA, Hodgson LC, Gutierrez AN, Wroe AJ, Panoff J
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42009110 · Publisher ↗
BACKGROUND: Postmastectomy radiation therapy (PMRT) may cause adverse events in the reconstruction setting. Proton-based PMRT is increasingly used and has been shown to improve cardiac and pulmonary dosimetry. Data on th...
BACKGROUND: Postmastectomy radiation therapy (PMRT) may cause adverse events in the reconstruction setting. Proton-based PMRT is increasingly used and has been shown to improve cardiac and pulmonary dosimetry. Data on the risk of capsular contracture (CC) with proton versus photon PMRT remain scarce. We compared the CC rate of the largest cohort of patients undergoing reconstruction after pencil beam scanning proton PMRT reported to date with an intensity modulated radiation therapy photon cohort, hypothesizing that the proton cohort would have a higher rate of CC. METHODS AND MATERIALS: An institutional review board -approved retrospective study was conducted on patients with breast cancer who underwent subpectoral 2-stage tissue expander/implant (TE/I) or direct-to-implant (DTI) breast reconstruction and received either pencil beam scanning proton or intensity modulated radiation therapy photon PMRT between January 2017 and December 2023 at 2 centers within a single institution. All patients undergoing TE/I had the TE irradiated. CC rates were estimated using the Kaplan-Meier method. Cox proportional hazards analysis, denoted as hazard ratios (HRs) with 95% CIs, was used to assess variables potentially associated with the outcome, and a binary logistic regression model was used to verify the results. RESULTS: The study cohort comprised 175 patients (89 proton; 86 photon). The median age was 49 years (range, 24-78), 63% were Hispanic. Patient demographics were well balanced between the groups, except in tumor laterality (P < .001) and reconstruction type (TE/I vs DTI; P < .001). The median follow-up was 42 and 47 months for the proton and photon groups, respectively. In a multivariable analysis, DTI patients had a significantly higher risk of CC compared with TE/I patients (HR, 3.0; 95% CI, 1.7-5.5; P < .001). Proton patients had a higher risk of developing CC compared with the photon group in univariate analysis (HR, 2.3; 95% CI, 1.26-4.30; P = .007), although this effect did not reach statistical significance in the multivariable model (HR, 1.76; 95% CI, 0.93-3.32; P = .083). The 2-year CC rate for patients treated with protons and DTI (n = 36), photons and DTI (n = 15), protons and TE/I (n = 53), and photons and TE/I (n = 71) was 50%, 35%, 23%, 12%, respectively (P < .001). No other factors were significantly associated with CC development. CONCLUSION: In this contemporary large proton versus photon PMRT cohort, patients treated with proton showed a trend toward an increased risk of CC. Patients undergoing DTI who were treated with protons had the highest risk of CC (50%). Careful consideration of reconstruction and radiation therapy modalities, assessing CC risk, and also involving patient input, is important for treatment selection.
UNICURE-HD: A Multicentric Retrospective Cohort Study of Single-Insertion Image-Guided high-Dose-Rate Brachytherapy for Locally Advanced Cervical Cancer in the Context of Limited Brachytherapy Access in France.
Houdou L, Bruand M, Laroze S … +8 more , Annede P, Meynard C, Monnier L, Encaoua J, Quintin K, Mavrikios A, Gardavaud F, Chargari C
Int J Radiat Oncol Biol Phys · 2026 Apr · PMID 42009109 · Publisher ↗
PURPOSE: To assess the feasibility, early outcomes, and toxicity of single-implant image-guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer in a multicenter French cohort; a pragmatic strategy to...
PURPOSE: To assess the feasibility, early outcomes, and toxicity of single-implant image-guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer in a multicenter French cohort; a pragmatic strategy to address limited and uneven access to utero-vaginal IGABT while preserving disease control and treatment safety. METHODS AND MATERIALS: We retrospectively analyzed 363 consecutive patients (Fédération Internationale de Gynécologie Obstétrique 2009 IB-IVA) treated with concurrent chemoradiation consisting of pelvic ± paraortic intensity modulated radiation therapy /volumetric modulated arc therapy (45 Gy in 25 fractions) with nodal boost to involved lymph nodes when indicated, followed by 1 applicator insertion delivering 4 high-dose-rate fractions. Planning was magnetic resonance imaging (MRI) guided with the applicator in place when available, otherwise computed tomography-guided with rigid fusion to an MRI performed a few days before. Composite doses were converted to equivalent doses per 2 Gy fractions, as per the linear-quadratic model. Outcomes (local control [LC], nodal and distant control, overall survival, and disease-free survival) were estimated by Kaplan-Meier from the end of radiation therapy. Late toxicity was graded according to the NCI-CTCAE version 5.0, with severe events defined as grade >= 3. RESULTS: T2b was the predominant T stage (59.5%), with nodal involvement in 47.9% of patients. The median overall treatment time (OTT) was 56 days (interquartile range, 50-61). Median D90-CTV (minimum dose delivered to 90% of the high-risk clinical target volume) was 85.9 Gy (IQR, 80.4-91.6 Gy). At a median follow-up of 20.2 months (range, 1.6-121 months), the Kaplan-Meier-estimated 3-year LC rate was 83.1% (95% CI, 76.4-88.0). At 36 months, LC was higher with MRI-centered than computed tomography-MRI fusion planning (93.5% [85.7-97.2] vs 78.5% [70.4-84.6]) on unadjusted Kaplan-Meier. LC rates were 94% for patients with an OTT <50 days, 89% for those with an OTT of 50 to 55 days, and 81% for patients with an OTT >55 days. Overall, grade ≥3 toxicity events occurred in 14.0% of the cohort. CONCLUSIONS: In this multicenter real-world cohort, LC was high overall, particularly among patients treated with MRI-centered, applicator-in-place brachytherapy planning. Single-implant high-dose-rate IGABT for locally advanced cervical cancer was feasible, providing outcomes broadly consistent with historical multi-insertion series in terms of side effects. Longer follow-up and expanded accrual will refine durability and prognostic analyses.
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