Bentzen SM, Gupta T, Jacinto AA
… +14 more, Rosenblatt E, Bhasker S, Napoles M, Binia S, Chansilpa Y, Aguiar S, Nagarajan M, Laskar SG, De Marchi P, Goloubeva O, Hopkins K, Zubizarreta E, Agarwal JP, Abdel-Wahab M
Beekman C, Morita S, Neibart S
… +4 more, Duda DG, Paganetti H, Grassberger C, Shih HA
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42315079
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PURPOSE: To investigate the impact of radiotherapy (RT) for brain tumors on circulating lymphocyte populations and understand this from a dosimetric perspective. METHODS: This prospective study enrolled primary brain tum...PURPOSE: To investigate the impact of radiotherapy (RT) for brain tumors on circulating lymphocyte populations and understand this from a dosimetric perspective. METHODS: This prospective study enrolled primary brain tumor patients treated with either photon or proton RT. To specifically study the effect of RT, only patients without concurrent chemotherapy were eligible. For each patient, blood samples were collected before, during and after RT, as well as at the first follow-up, for flow cytometry analysis of blood cells. We used a stochastic model to compute blood dose distributions from treatment plans and patient-specific blood flow simulations. Dose to the lymph nodes in the head and neck region was also assessed. Dose distributions and lymphocyte trends from patients treated with photon versus proton therapy were compared. RESULTS: Thirty-five patients with a median age of 50 were included: 27 patients with benign tumors (mostly meningiomas) and 8 with malignant tumors (mostly gliomas). There were no significant RT-induced changes in either the total lymphocyte count or its subpopulations in this patient cohort. In line with this finding, dosimetric analyses showed that total blood doses were ∼0.1-0.2 Gy and that most lymph nodes in the head-and-neck area are spared. Proton RT was associated to a greater dosimetric sparing of both blood and lymph nodes. CONCLUSION: In this exploratory analysis, we found no evidence that RT alone results in significant changes in peripheral lymphocyte counts in primary brain tumor patients treated to limited intracranial volumes. The lack of apparent RT-induced cytotoxicity is consistent with the limited dose received by either the blood or the regional lymph nodes.
Smith GL, Wu CF, Joyner M
… +32 more, Schlembach PJ, Bloom ES, Reed VK, Graybill J, Anderson C, Lin R, Dragun A, Ceilley E, Garg AK, Freeman A, Diavolitsis V, Mayo L, Bowers J, Neisler K, Reddy J, Ahlawat S, Khan M, Mitchell M, Arzu I, Tsuji SY, DeHaan M, Jain S, Greenwalt J, Rehman S, Zaki M, Wei SJ, Chavez-MacGregor M, Giordano SH, Shen Y, Kaiser KW, Smith BD, OPAL-II Investigators’ Group
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42297155
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PURPOSE: Within a randomized clinical trial comparing partial breast irradiation (PBI) dosing schedules, we sought to determine whether shortening the radiation course would reduce financial toxicity (FT). METHODS AND MA...PURPOSE: Within a randomized clinical trial comparing partial breast irradiation (PBI) dosing schedules, we sought to determine whether shortening the radiation course would reduce financial toxicity (FT). METHODS AND MATERIALS: In a phase 3 trial of 778 women aged ≥40 years who underwent segmental mastectomy for early breast cancer at 12 US cancer centers, patients were randomized 1:1 to external beam PBI using 15-22 fractions (control, n = 385) versus 513 fractions (experimental, n = 393) (NCT03077841). FT was assessed using comprehensive, multi-item instruments and scored using the Economic Strain and Resilience in Cancer measure at baseline, end of radiation treatment (EoT), and 6- and 18-months after radiation on a scale of 0-100 (higher score indicated worse FT). Mixed linear multivariable regression estimated adjusted difference-in-differences between EoT versus baseline FT by treatment arm. Minimal important difference (MID) in Economic Strain and Resilience in Cancer score from baseline to EoT was estimated, anchored on change in patient-reported overall financial situation during that interval. RESULTS: Treatment arms had balanced clinical and sociodemographic characteristics. Median PBI duration was 22 days (IQR, 21-25) for the control arm versus 7 days (IQR, 5-10) for the experimental arm (P < .001). FT measures were completed for 96.1% of baseline and EoT assessments (n = 1496/1556). Adjusted improvement in FT score between baseline to EoT was -2.0 (95% CI, -3.6 to -0.4; P = .02) for the experimental versus control arm. Of 52 individual FT items assessed, 9 favored the experimental arm at EoT (P < .05), whereas none favored the control arm. MID in Economic Strain and Resilience in Cancer score was 2.2 (95% CI, 1.0-3.4). CONCLUSIONS: For patients with early breast cancer eligible for PBI, shortening the radiation duration by an average of 15 days yielded a reduction in end of treatment FT that was less than the MID estimated in this study.
Li X, Wu Y, Zhang Y
… +5 more, Ge M, Zou S, Zhang R, Zhou S, Wang J
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42288290
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PURPOSE: The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in lung cancer patients remains uncertain. The goal of this study was to conduc...PURPOSE: The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in lung cancer patients remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. MATERIALS AND METHODS: A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. RESULTS: A total of 80 studies including 21,645 patients were analyzed. Of these, 25 studies reported cardiac events, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: 1) LAD V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses were significantly associated with ischemic events. 2) Multiple CS parameters were associated with different arrhythmia subtypes. 3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion.4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. 5)We also identified several threshold with potential predictive values, such as LAD V15<10% for MACE, LPV V55 <2% and RPV V10 < 54% for atrial fibrillation (AF), RA V60<0.03cc for non-AF supraventricular tachyarrhythmia (SVT), and LMA V10≥1cc for bradyarrhythmia. CONCLUSION: This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42288289
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INTRODUCTION: Brainstem necrosis is a rare but serious toxicity following radiotherapy for pediatric brain tumors. In proton therapy (PT), concerns have emerged around elevated linear energy transfer (LET) and the relati...INTRODUCTION: Brainstem necrosis is a rare but serious toxicity following radiotherapy for pediatric brain tumors. In proton therapy (PT), concerns have emerged around elevated linear energy transfer (LET) and the relative biological effectiveness (RBE) in relation to normal tissue damage. While previous studies have largely focused on asymptomatic image changes in adults, we investigated voxel-wise correlations between dose, LET, and symptomatic brainstem necrosis in a pediatric case-control cohort. MATERIALS AND METHOD: From a cohort of exactly 1200 central nervous system (CNS) tumor patients treated with double scattering proton therapy between 2006 and 2023, 48 patients were included in a case-control cohort. Twelve of these patients had developed brainstem necrosis following PT and 36 were matched controls (1:3 case-control ratio). Necrotic volumes were contoured on magnetic resonance images (MRI) and related to LET and RBE-weighted dose distributions from Monte Carlo simulations. Mixed effect modelling was used to investigate potential correlations between dose, LET and necrosis at voxel-level while accounting for intergroup heterogeneities. Further, a recently published prediction model for MRI contrast enhancement in posterior fossa tumor patients was utilized to evaluate whether its parameters demonstrated predictive value within our cohort. To control for dose, voxel matching was also performed between necrotic and healthy voxels to investigate LET, and LET-weighted doses were calculated and compared. RESULTS: Mean dose in necrotic brainstem voxels was 54.1 Gy(RBE) [range: 17.7-58.7 Gy(RBE)] compared to 42.6 Gy(RBE) [0.0-63.1 Gy(RBE)] in healthy voxels. Mean LET in necrotic brainstem voxels with dose over 54 Gy(RBE) was 2.9 keV/µm [2.2-5.0 keV/µm] in necrotic voxels and 2.7 keV/µm [1.9-5.0 keV/µm] in healthy voxels. Mixed effect modelling revealed a significant positive interaction between dose and LET, indicating that elevated LET was associated with an increased probability of necrosis in high-dose regions. However, notable intergroup heterogeneities were observed, with more pronounced LET-related trends in specific case-control pairs. Dose matching similarly only found higher LET in the necrotic voxels of a subset of the case-control groups. The prediction model estimated higher probability of contrast-enhancement in the necrotic voxels, primarily driven by dose and most necrotic voxels being located in the brainstem pons. LET-weighted dose was significantly elevated in necrotic voxels compared to healthy voxels. CONCLUSION: Brainstem necrosis was primarily driven by dose, with elevated LET contributing to increased risk in high-dose regions. Nevertheless, considerable intergroup heterogeneity was observed, and dose-matched analyses did not support a uniform LET effect.
Martin CJ, Gros S, Kron T
… +5 more, Wood T, Vassileva J, Fourie H, Djukelic M, Small JW
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42288288
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Realisation of the full potential of external beam radiation therapy requires accurate targeting, which in turn depends on frequent imaging of patients immediately prior to or during treatment. These verification images...Realisation of the full potential of external beam radiation therapy requires accurate targeting, which in turn depends on frequent imaging of patients immediately prior to or during treatment. These verification images may expose normal tissues surrounding the tumour to additional radiation. Although imaging doses are substantially lower than therapeutic doses, irradiated volumes are larger and repeated exposure carries a non-negligible risk of inducing second primary cancers in adjacent tissues and other late effects, particularly in younger patients with longer life expectancies. Cone beam computed tomography (CBCT) with kilovoltage systems mounted on linear accelerators is the modality used most widely for verification in image guided radiotherapy (IGRT). In contrast to diagnostic radiology, where imaging parameters are adjusted routinely to optimise radiological protection for individual patients, radiotherapy departments often use vendors' supplied default protocols with limited optimisation. As imaging is often performed at every fraction, there is considerable scope for further optimisation of radiological protection. However, information about doses from CBCT imaging, which is a prerequisite, is frequently not available. In diagnostic radiology, imaging dose management is supported by routine surveys of standardized dose indices and the use of diagnostic reference levels (DRLs) for benchmarking practice. This paper reviews the methods used in diagnostic radiology and considers how a similar approach might be applied to patient imaging doses in radiotherapy. It identifies appropriate dose quantities such as the Cone Beam Dose Index (CBDI) and wide beam Computed Tomography Dose Index (CTDI) that might be used for surveying and benchmarking imaging dose levels. It sets out actions that will be needed to initiate optimisation to balance image quality requirements against patient doses and discusses the next phase of setting up radiotherapy specific dose reference levels. Establishing such reference levels can raise awareness, support systematic imaging dose reduction, and improve the safety and effectiveness of IGRT.
Damian-Jacobo EA, Chi X, Ludmir EB
… +5 more, Chino F, Lin R, Koay EJ, Lee A, Wu SY
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42276425
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PURPOSE: Advanced radiation oncology techniques such as proton therapy allow more precise treatment delivery, with improved toxicity profiles; however, insurance coverage is variable. In addition to direct treatment-rela...PURPOSE: Advanced radiation oncology techniques such as proton therapy allow more precise treatment delivery, with improved toxicity profiles; however, insurance coverage is variable. In addition to direct treatment-related costs, radiation treatment contributes to the financial toxicity of cancer treatment through indirect costs such as lodging, lost wages, and travel. GoFundMe is a leading crowdfunding platform, with one-third of donations supporting health care costs. We sought to identify characteristics of proton crowdfunding campaigns that met their fundraising goal. METHODS AND MATERIALS: GoFundMe was queried for fundraisers with keywords such as proton therapy, proton radiation from February 2024 to March 2025. Details, such as treatment site, patient demographic characteristics, and use of funds, were abstracted from the campaign website. Campaigns were considered fulfilled if they met 100% of the goal. RESULTS: Six hundred ninety-nine campaigns were included in this analysis, with a median fundraising goal of $20,000 (IQR, $10,000-$40,000) and a median amount raised of $7790 (IQR, $3470-$15,418). The most common malignancies noted in campaigns were of the central nervous system (45%, 313/699), followed by head and neck (16%, 108/699). Twenty-two percent of campaigns (150/699) noted that proton therapy was not covered by insurance, which was associated with a greater likelihood of being fully funded (P = .023). Campaigns with links to additional information (hospital where proton therapy would be delivered, and external sites with information about the malignancy being treated) were also more likely to be fully funded (P = .021). On univariate analysis, pediatric beneficiaries and lack of insurance coverage for proton therapy were associated with funds raised (P ≤ .001 for both). CONCLUSIONS: Crowdfunding may be a financial safety net for patients with cancer. The success of crowdfunding campaigns may be influenced by patient demographics, insurance coverage, and donor engagement.
Teng YC, Cao Y, Zhu X
… +12 more, Huo L, Hong J, Lin X, Lai Y, Zhou P, Bian Y, Chen J, Zhong W, Ping J, Lin Q, Pan J, Liu YH
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42276424
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PURPOSE: To evaluate whether mucosal boron heterogeneity measured using fluoro-boronophenylalanine positron emission tomography (F-BPA PET) improves the prediction of oral mucositis in boron neutron capture therapy (BNCT...PURPOSE: To evaluate whether mucosal boron heterogeneity measured using fluoro-boronophenylalanine positron emission tomography (F-BPA PET) improves the prediction of oral mucositis in boron neutron capture therapy (BNCT), and to establish an imaging-guided framework for normal tissue complication probability (NTCP) modeling. METHODS AND MATERIALS: This retrospective study analyzed 45 BNCT treatment sessions for head and neck cancer. Pre-treatment F-BPA PET was used to quantify PET-derived mucosal uptake and to derive an uptake-defined mucosal region using a tissue-to-blood ratio (TBR) threshold of 1.8. Four mucosal dose-calculation workflows were compared: (1) the Finnish workflow and (2) the Japanese workflow-both delineating mucosa anatomically and assuming uniform boron concentration implemented via a fixed TBR; (3) anatomical mucosa and (4) uptake-defined mucosa with heterogeneous boron distribution derived from PET-derived uptake heterogeneity. Biological (Gy-equivalent) and physical (Gy) subvolume dose metrics, including dose to the hottest 0.05 cubic centimeters (D), were evaluated for correlation with mucositis severity, discrimination of grade ≥ 2 toxicity, and suitability for NTCP modeling. RESULTS: F-BPA PET demonstrated pronounced functional heterogeneity across the mucosa. Among all evaluated metrics, only the uptake-defined biological D showed a significant monotonic association with toxicity and fulfilled all NTCP validity criteria, yielding the highest discriminative performance (area under the curve 0.765 ± 0.025) and physiologically plausible TD-TD thresholds (4.85-12.84 Gy-equivalent). In contrast, Finnish and Japanese anatomical maximum-dose metrics, based on uniform-boron assumptions, showed no meaningful correlation with clinical outcomes. CONCLUSIONS: Functional PET imaging reveals clinically important mucosal heterogeneity that influences BNCT toxicity. The uptake-defined biological D demonstrated superior prediction of oral mucositis and may provide a promising hypothesis-generating framework for developing patient-specific mucosal dose constraints, pending prospective validation.
Jollota SP, Dragojevic S, Remmes NB
… +10 more, Radtke JL, Singh J, DeWerd LA, Sawakuchi GO, Reis MTF, Pandey MK, Lou Z, Mutter RW, Khan AU, Callaghan CM
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42269790
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PURPOSE: To expand preclinical efforts aimed at understanding the unique radiobiology of high linear energy transfer alpha particles and their implications for cancer therapy, robust, accessible, and high-throughput in v...PURPOSE: To expand preclinical efforts aimed at understanding the unique radiobiology of high linear energy transfer alpha particles and their implications for cancer therapy, robust, accessible, and high-throughput in vitro alpha irradiation platforms are needed. Such platforms must be extensively characterized and validated to ensure rigor and reproducibility. Here, we describe the construction and dosimetric characterization of a benchtop in vitro alpha irradiation platform using an americium 241 (Am) source. METHODS AND MATERIALS: A square foil with embedded Am was used as the alpha source (activity 3.3785 mCi). The source was secured in the roof of a custom housing incorporating a 3-dimensional printed microcapillary array collimator to exclude large-angle alpha particles, thereby narrowing the energy spectrum and improving homogeneity. A movable shelf accommodates cells grown on glass slides at variable distances from the source. Dosimetric characterization included direct measurement of dose homogeneity, source self-attenuation, energy spectra, absorbed dose, and dose rate. RESULTS: The Am source, when used in conjunction with the microcapillary array, provided a spatially uniform and geometrically stable irradiation field. The mylar entrance window resulted in predictable shifting and broadening of the alpha particle energy spectra. Absorbed dose and dose-rate measurements (5.815-7.721 mGy/s) demonstrated the feasibility of controlled in vitro alpha particle irradiation studies. CONCLUSIONS: We established a turnkey, low-cost in vitro alpha irradiation platform suitable for high-throughput preclinical studies. The homogeneity, alpha particle energy spectra, absorbed dose, and dose rate were characterized and validated through direct measurements. Given the approximately 432-year half-life of Am, this platform will provide stable and reliable dose rates for decades, facilitating long-term radiobiological investigations.
Gergelis KR, Afzal A, Mullikin TC
… +11 more, Harmsen WS, Remmes NB, Tseung HSWC, Shiraishi S, Barnes J, Elbanna M, Garda AE, Park SS, Corbin KS, Mutter RW, Shumway DA
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42269789
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PURPOSE: We sought to compare target coverage, skin dose, physician-assessed adverse events, and patient-reported skin outcomes in a large cohort of patients receiving postmastectomy intensity modulated proton therapy (I...PURPOSE: We sought to compare target coverage, skin dose, physician-assessed adverse events, and patient-reported skin outcomes in a large cohort of patients receiving postmastectomy intensity modulated proton therapy (IMPT) or photon radiation therapy (XRT). METHODS AND MATERIALS: Women with unilateral, noninflammatory breast cancer treated with postmastectomy radiation therapy using IMPT or XRT to 50 Gy relative biological effectiveness (RBE) were included. Skin planning objectives for both modalities prioritized ≥90% of the skin volume receiving >90% of the prescription dose, which is expected to control microscopic disease, while maintaining dose homogeneity. IMPT planning objectives limited the dose to 1 cc of skin to ≤105% of the prescription dose, with an ideal constraint of ≤96%. Target and skin dosimetry were evaluated. Acute Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 dermatitis and skin-specific patient-reported outcomes using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) were compared between modalities. RESULTS: Among 176 women (93 IMPT, 83 XRT), the median skin D0.01cc, D1cc, and D10cc were higher in XRT plans than in IMPT plans, although the differences were all less than 3%. Acute grade ≥2 dermatitis occurred in 47% (IMPT) and 48% (XRT) and was not associated with treatment modality (P = .91). Grade 3 dermatitis occurred in 3% (IMPT) and 7% (XRT) (P = .22), with no grade 4 events. At 12 months post-RT, XRT patients reported more skin color changes than IMPT patients (26% vs 6%, P = .04), the only significantly different patient-reported skin outcome. CONCLUSIONS: Patient and provider-reported adverse skin events were mild and comparable between IMPT and XRT. These findings highlight the importance of skin constraints for IMPT planning to titrate an optimal skin dose.
Zakharia A, Kabarriti R, Bodner WR
… +5 more, Mehta KJ, Halmos B, Kalnicki S, Garg M, Ohri N
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42269788
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Wearable activity monitors provide objective assessment of physical activity, yet long-term data following curative-intent chemoradiotherapy remain limited. We enrolled 17 cancer survivors a mean of 5.4 years (range, 4.2...Wearable activity monitors provide objective assessment of physical activity, yet long-term data following curative-intent chemoradiotherapy remain limited. We enrolled 17 cancer survivors a mean of 5.4 years (range, 4.2-7.3) after chemoradiotherapy and compared wearable-derived step count averages at baseline and long-term follow-up. Fourteen participants (82%) had lower step counts at follow-up compared with baseline, with a median relative decline of -43% (IQR, -65% to -23%), corresponding to a median annualized rate of -12% per year. No patient- or disease-related characteristics were significantly associated with activity change in the full cohort. In the lung cancer subset (n=9), higher mean heart radiotherapy dose was associated with greater activity decline (coefficient -2.7 per Gy; p=0.034). Physical activity remains substantially reduced among long-term cancer survivors following curative-intent chemoradiotherapy, and conventional clinical factors showed limited ability to predict this decline.
Ku GY, Winter K, Ilson D
… +12 more, Adusumilli PS, Nishimura M, Yock AD, Mehta RJ, Biran T, Frakes JM, Wu A, Miller ED, Klempner SJ, Moughan J, Hong TS, Williams TM
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42269787
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INTRODUCTION: Definitive chemoradiation (CRT) is standard for patients with medically inoperable esophageal cancer. OBP-301 is a modified adenovirus that adds a human telomerase reverse transcriptase gene promoter, repli...INTRODUCTION: Definitive chemoradiation (CRT) is standard for patients with medically inoperable esophageal cancer. OBP-301 is a modified adenovirus that adds a human telomerase reverse transcriptase gene promoter, replicating only in tumor cells to cause lysis. METHODS: In this phase 1 study, OBP-301 was added to carboplatin/paclitaxel and RT (50.4 Gy). Patients received intra-tumoral OBP-301 via endoscopy 3 days prior to and then at Days 12 and 26 of RT. The primary endpoint was protocol-defined dose-limiting toxicity (DLT). Secondary endpoints included clinical complete response (cCR) rate, number alive and alive without progression at 1 year. RESULTS: From June 2020 to July 2024, 15 evaluable patients were enrolled. Fourteen patients (93%) received all planned OBP-301 injections and 50.4 Gy RT. No DLTs were observed. The most common treatment-related grade 3/4 toxicities were neutropenia (40%) and lymphopenia (33%). Two patients died prior to restaging: 1 patient developed grade 5 respiratory failure 6 weeks after CRT (suspected RT pneumonitis), while a second patient had unrecognized airway involvement at baseline, which led to a tracheoesophageal fistula during Week 3 of CRT. The cCR rate for patients undergoing restaging (n=13) was 100% (95% CI: 77, 100), and 87% (95% CI: 62, 96) for all 15 patients. At 1 year, 9 (60%) out of 15 patients are still alive and 8 (53%) are alive without progression. CONCLUSIONS: OBP-301 administration before and during CRT is feasible and safe, resulting in a very promising cCR rate. A randomized study is being planned to further evaluate safety and efficacy.
Zhu X, Zhao L, Zhang S
… +7 more, Guo H, Jiang N, Zhang H, Jiang F, Ding N, Ren B, Li M
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42264097
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PURPOSE: Chemoradiation therapy is standard for unresectable stage III non-small cell lung cancer (NSCLC). This phase 1b study assessed the safety and surgical conversion of neoadjuvant low-dose stereotactic body radiati...PURPOSE: Chemoradiation therapy is standard for unresectable stage III non-small cell lung cancer (NSCLC). This phase 1b study assessed the safety and surgical conversion of neoadjuvant low-dose stereotactic body radiation therapy (SBRT)-based radiation therapy followed by pembrolizumab and chemotherapy in patients with potentially resectable stage III NSCLC. METHODS AND MATERIALS: Patients deemed potentially resectable by the multidisciplinary team received neoadjuvant low-dose SBRT-based radiation therapy to the primary tumor (24 Gy for peripheral lesions and 12 Gy for central lesions) delivered in 3 fractions. Selective planning target volumes were applied to spare critical structures and optimize surgical safety. Two cycles of 100-mg pembrolizumab plus platinum-based chemotherapy followed. Surgical feasibility was evaluated by the second multidisciplinary team 4 to 6 weeks after neoadjuvant therapy. The primary endpoint was safety; secondary endpoints included pathological complete response, progression-free survival, and overall survival. RESULTS: Seventeen patients received neoadjuvant therapy, with no dose-limiting toxicities observed. Across the overall treatment course, grade 3 to 5 treatment-related adverse events were reported in 5 patients (29.4%), most commonly grade 3 leukopenia (2 patients, 11.8%), and included 1 grade 5 surgical event due to fatal pulmonary artery hemorrhage. Objective responses were noted in 16 patients (94.1%). Surgery was successfully conducted in 11 patients (64.7%), with 10 (90.9%) achieving R0 resection. Six patients (54.5%) achieved pathological complete response. At a median follow-up of 22.8 months (95% CI, 18.9-26.7), the median progression-free survival was 29.0 months (95% CI, 18.1-39.9), and median overall survival was 37.9 months (95%CI, 21.9-53.9). CONCLUSIONS: Neoadjuvant low-dose SBRT-based radiation therapy followed by pembrolizumab and chemotherapy is tolerable and demonstrates promising rates of surgical conversion and pathological response in patients with potentially resectable stage III NSCLC.
Reichl S, Kirisits C, Lindegaard JC
… +7 more, Mahantshetty U, Schmid M, Pötter R, Jürgenliemk-Schulz IM, Wulff C, Sturdza A, Petric P
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42264096
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BACKGROUND: Gynecological reirradiation using brachytherapy (GRIB) represents an important salvage therapy for loco-regionally recurrent gynecologic cancers in previously irradiated patients. This systematic review aimed...BACKGROUND: Gynecological reirradiation using brachytherapy (GRIB) represents an important salvage therapy for loco-regionally recurrent gynecologic cancers in previously irradiated patients. This systematic review aimed to evaluate current evidence on GRIB with a focus on reporting practices, identify literature gaps, and propose a framework to optimize future GRIB reporting. METHODS: A systematic literature search was conducted in PubMed/MEDLINE according to PRISMA guidelines from January 1990 to September 2025. Full English-language publications addressing GRIB were included, excluding case reports, guidelines, reviews, adjuvant GRIB studies, and duplicate publications. Two independent reviewers screened 161 records, with supplementary citation screening identifying additional publications. Reporting patterns were extracted using a template based on the ESTRO/EORTC consensus statement on reirradiation. RESULTS: A total of 50 original publications, including 1978 patients (71% underwent reirradiation), were analyzed. Most studies were retrospective (92%) with small sample sizes (mean: 28.2 patients). Modern GRIB techniques demonstrate encouraging local control (35%-87% at 1 year, 26%-59% at 5 years) and overall survival rates (52%-83% at 1 year, 34%-54% at 5 years), although accompanied by grade 3 or 4 late toxicity rates ranging from 0% to 33%. Significant heterogeneity existed across tumor types, treatment protocols, and reporting practices. Critical parameters, including treatment intent, target aims, organ-at-risk constraints, and quality-of-life outcomes, were inconsistently or incompletely reported. Radiobiological uncertainties and dose-summation challenges further complicate the interpretation of published results. CONCLUSIONS: GRIB is a reasonable salvage option for selected recurrent gynecologic tumors. Despite advances in image-guided adaptive brachytherapy, the interpretation of available GRIB literature remains challenging because of inconsistent reporting practices, small sample sizes, and heterogeneous treatment protocols. Multi-institutional prospective protocols with standardized reporting, development of dose-summation models, and research addressing radiobiological aspects are essential to generate reliable evidence for guiding future clinical practice.