PURPOSE: FLASH radiation therapy (FLASH-RT) can achieve tumor control comparable to conventional dose-rate irradiation (CONV-RT) while reducing radiation damage to normal tissues. However, the physical conditions trigger...PURPOSE: FLASH radiation therapy (FLASH-RT) can achieve tumor control comparable to conventional dose-rate irradiation (CONV-RT) while reducing radiation damage to normal tissues. However, the physical conditions triggering the FLASH sparing effect remain unclear, and mechanisms related to oxidative stress and redox regulation are poorly understood. This study aimed to investigate the physical parameters and redox-related molecular mechanisms responsible for the FLASH effect. METHODS AND MATERIALS: This study uses a murine acute intestinal toxicity model to investigate how beam parameters influence the FLASH sparing effect and tumor control using innovative FLASH-RT and CONV-RT combined irradiation. We integrated kinetic simulations, experimental measurements of oxidative stress and lipid peroxidation, antioxidant interventions, RNA sequencing, nuclear factor E2-related factor 2 (NRF2) knockout mice and molecular analyses to elucidate the involved pathways. RESULTS: The results demonstrate that a substantially reduced FLASH dose can still elicit the sparing effect, provided a total dose threshold is met. Kinetic simulation and experimental validation demonstrate that FLASH-RT enhances peroxyl radical recombination, reducing oxidative stress and lipid peroxidation. Antioxidant interventions further confirm the essential role of free radicals. Molecular profiling revealed that FLASH-RT activates the NRF2 antioxidant pathway while suppressing ERK signaling, thereby enhancing cellular redox defenses, reducing apoptosis, and mitigating radiation-induced tissue injury. CONCLUSIONS: These findings highlight the feasibility of optimizing the FLASH-RT therapeutic window through redox modulation and provide a foundation for developing free radical-targeted strategies to improve its therapeutic efficacy.
Hiya-Kawaguchi U, Endo M, Nakagawa M
… +12 more, Ogawa K, Irie D, Takahashi S, Nagase D, Nakamura M, Shibayama C, Fukuda Y, Kawahara M, Akahane K, Takahashi Y, Mori H, Shirai K
PURPOSE: Bone oligometastases are increasingly recognized as a clinical entity that may benefit from local therapies. Stereotactic body radiation therapy (SBRT) enables the delivery of high-dose, precise irradiation and...PURPOSE: Bone oligometastases are increasingly recognized as a clinical entity that may benefit from local therapies. Stereotactic body radiation therapy (SBRT) enables the delivery of high-dose, precise irradiation and has shown promising results in improving local control (LC) and survival. However, prognostic factors influencing LC after SBRT in patients with bone oligometastases treated with curative metastasis-directed intent remain unclear. METHODS AND MATERIALS: We retrospectively analyzed 58 patients with 68 bone oligometastatic lesions treated with SBRT between March 2021 and December 2023. Radiation therapy protocols were determined according to lesion site, and follow-up imaging was performed every 3 months. Overall survival was evaluated using the Kaplan-Meier method, and LC was assessed using a competing risk model. Prognostic factors for LC were investigated using univariate and exploratory multivariable analyses, with gross tumor volume (GTV) cutoffs determined by receiver operating characteristic analysis using local recurrence as the endpoint. RESULTS: The median follow-up duration was 25 months. The 1- and 2-year overall survival rates were 95% and 80%, respectively. The 1- and 2-year LC rates were 86.1% and 80.3%, respectively. Upon exploratory multivariable analysis, a GTV ≥ 12 cc was identified as an independent predictor of local recurrence (adjusted hazard ratio, 8.77; 95% CI, 1.10-70.2; P = .041). Lesions with GTV ≥ 12 cc had significantly lower LC rates than those with GTV < 12 cc (Gray's test, P = .013). No grade ≥3 treatment-related adverse events were observed. CONCLUSIONS: SBRT for bone oligometastases provides excellent LC and survival with minimal toxicity. Larger tumor volume, as assessed by GTV, was associated with a higher risk of local recurrence in this cohort. Further studies are warranted to validate these findings and to explore volume-adapted treatment strategies.
Int J Radiat Oncol Biol Phys
· 2026 May · PMID 42000362
·
Publisher ↗
Stereotactic body radiation therapy (SBRT) is an emerging therapeutic modality in modern oncology, offering highly conformal, ablative radiation in a few fractions. However, implementing SBRT in limited-resource settings...Stereotactic body radiation therapy (SBRT) is an emerging therapeutic modality in modern oncology, offering highly conformal, ablative radiation in a few fractions. However, implementing SBRT in limited-resource settings presents substantial challenges. This editorial describes the current SBRT landscape in the Philippines, a large lower-middle-income country in Southeast Asia with a rising cancer burden but constrained radiation therapy capacity. Of the 62 radiation therapy centers nationwide, only 14 (25%) have SBRT-capable technology, all privately operated and largely concentrated in the National Capital Region. SBRT remains markedly underutilized because of limitations in infrastructure, trained personnel, and patient access. As SBRT capacity continues to expand, we highlight the importance of establishing sustainable, comprehensive SBRT programs that incorporate robust clinical and technical quality assurance and outline practical strategies relevant to limited-resource settings, including streamlined workflows, hub-and-spoke care models, collaborative partnerships, strengthened data infrastructure, and equitable financing mechanisms. The commitment of dedicated practitioners and leadership from the national professional society will be essential to expanding safe, high-quality SBRT access in the Philippines.
PURPOSE: To introduce a novel cognition-sparing stereotactic radiosurgery (SRS) planning framework that limits dose to the cognitive connectome (10 bilateral white matter tracts, the corpus callosum, and the hippocampi)...PURPOSE: To introduce a novel cognition-sparing stereotactic radiosurgery (SRS) planning framework that limits dose to the cognitive connectome (10 bilateral white matter tracts, the corpus callosum, and the hippocampi) and to demonstrate its capability to preferentially spare the cognitive domains of memory, language, executive function, attention, and fine motor control. METHODS AND MATERIALS: Three cases representing the spectrum of intracranial disease treated with SRS (intact metastases, postoperative cavity, and arteriovenous malformation) and presenting competing domain-specific priorities based on lesion location were selected from the phase 2 cognition-sparing SRS (COG-SRS) trial. The cognitive connectome was autosegmented using AtlasTrack (white matter tracts) and FreeSurfer/FastSurfer (hippocampi) and registered to the computed tomography simulation scan. For each case, a standard plan, 4-6 domain-optimized plans, and an all-domain composite plan were generated using noncoplanar volumetric modulated arc therapy. All plans were required to meet target coverage and conventional organ-at-risk constraints. Dose to domain-specific structures and plan quality metrics were compared to quantify achievable dose sparing and dosimetric trade-offs. RESULTS: Domain-optimized plans consistently reduced dose to structures supporting the prioritized domain, with expected cross-domain trade-offs. The all-domain composite plan produced the most balanced reductions across eloquent structures. When lesions abutted cognition-critical structures, D reductions were limited. However, substantial D reductions were still achieved. All plans maintained standard target coverage, with generally small differences in plan quality indices relative to standard planning. Plan complexity varied across domain-specific optimizations, reflected by differences in monitor units. CONCLUSIONS: Cognition-sparing SRS that limits dose to the widely distributed cognitive connectome while maintaining target coverage is feasible and allows for a domain-tunable approach applicable across common SRS indications. This flexibility supports a patient-centered paradigm, in which cognitive priorities are incorporated through shared decision-making. Using standard magnetic resonance imaging sequences and automated segmentation, the technique is readily translatable, and an open-access website (www.cogsrs.com) has been created to facilitate dissemination.
PURPOSE: Palliative radiation therapy (RT) is widely used for symptom control across diverse clinical settings. In routine practice, however, post-treatment evaluation may not be consistently documented. We examined real...PURPOSE: Palliative radiation therapy (RT) is widely used for symptom control across diverse clinical settings. In routine practice, however, post-treatment evaluation may not be consistently documented. We examined real-world patterns of response documentation after palliative RT and identified episodes that were clinically evaluable but not formally evaluated. METHODS AND MATERIALS: We retrospectively reviewed 309 treatment episodes of palliative RT delivered between September 2018 and March 2019. Clinical records were examined to determine whether radiation oncologist-authored documentation was present within 16 weeks after RT. Follow-up duration was compared between radiation oncologists and non- radiation oncology providers. Episodes were classified as evaluated, nonevaluable (death or loss to follow-up within 60 days), or evaluable but not evaluated (EBNE; survival beyond 60 days with continued institutional follow-up but no radiation oncologist-authored documentation within 16 weeks). RESULTS: Among 309 treatment episodes (median age, 64.5 years), radiation oncologist-authored documentation was observed in 199 episodes (64.4%). Follow-up duration ranged from 0 to 413 days (median, 75 days) for radiation oncologists and from 0 to 418 days (median, 110.5 days) for non-radiation oncology providers (log-rank P < .0001). Forty-seven episodes (15.2%) were classified as nonevaluable. Among the remaining 262 evaluable episodes, 63 (24.0% of evaluable; 20.4% of total) had no radiation oncologist-authored documentation within 16 weeks despite survival beyond 60 days and were categorized as EBNE. EBNE occurred across treatment sites, including bone and brain indications. CONCLUSIONS: A substantial proportion of clinically evaluable palliative RT episodes lacked radiation oncologist-authored documentation. The EBNE framework offers a reproducible method to separate documentation-based nonevaluation from clinical infeasibility, improving transparency in the interpretation of real-world palliative RT outcomes.
Lukens JN, Riina MD, Weinstein G
… +25 more, MacDuffie E, Ramkissoon A, Baron J, Berger M, Messing I, Gentile M, Maxwell R, Ojerholm E, Swisher-McClure S, Santos AG, Porier K, Basu D, Brody R, Cannady S, Carey R, Chalian A, Newman J, Rajasekaran K, Rassekh C, Shanti R, Cohen RB, Singh A, Sun L, Montone K, Lin A
PURPOSE: We conducted a phase 2 clinical trial reducing both dose and volume of adjuvant radiation in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We also examined wh...PURPOSE: We conducted a phase 2 clinical trial reducing both dose and volume of adjuvant radiation in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We also examined whether postoperative circulating tumor DNA (ctDNA) was prognostic for outcomes. METHODS AND MATERIALS: Eligible patients had pT0 to pT3 pN0 to pN1 HPV-associated OPSCC (American Joint Committee on Cancer 8th edition) treated with primary transoral robotic surgery and neck dissection. Adjuvant radiation therapy (RT) was delivered in 25 fractions over 5 weeks. We reduced RT volumes in 2 ways: the primary oropharyngeal resection bed was omitted in select patients (pT1-T2 tumors with negative margins and no lymphovascular invasion or perineural invasion), and the contralateral neck targets were reduced to mirror the pathologically involved ipsilateral nodal levels. We also reduced RT doses: 50 Gy was given to primary resection beds requiring treatment and to ipsilateral neck levels with pathologically positive nodes; 45 Gy was delivered to other at-risk ipsilateral nodal regions and the contralateral neck. Concurrent chemotherapy was prescribed for positive margins and extranodal extension, although optionally omitted when extranodal extension was ≤1 mm. Baseline HPV ctDNA was collected after surgery and measured at 3 subsequent timepoints. RESULTS: We enrolled 150 patients between October 2018 and June 2022. One patient withdrew, leaving 149 patients treated per protocol. At a median follow-up of 48 months (IQR, 38-59 months), no patients developed local recurrence while 2 experienced regional recurrences. The estimated 5-year locoregional control (LRC) rate was 98.0% (95% CI, 95.3%-100%). Both regional recurrences were successfully salvaged. Ten patients (6.7%) developed distant metastases, and 3 (2.0%) died of disease. At 24 months post-RT, the median MD Anderson Symptom Inventory for head and neck cancer scores were dysphagia-2, xerostomia-2, and interference with work-0. For 79 patients with available blood samples, detectable postoperative HPV ctDNA was associated with subsequent metastatic disease but not LRC. CONCLUSIONS: Now with mature follow-up, our adjuvant RT strategy with reduced doses and volumes maintained high LRC with favorable toxicity in selected patients with HPV-associated OPSCC.