共找到 20 条结果
暂无摘要（点击查看详情）
Definitive radiation therapy for cervical cancer results in significant vaginal and sexual toxicity. Prior work has investigated dosimetric predictors of vaginal toxicity; however, sexual health outcomes are lacking. Patients with stage IB to IVA cervical cancer treated with definitive chemoradiation and magnetic resonance-guided brachytherapy were enrolled in a prospective, cross-sectional study. Sexual toxicity was assessed using 2 validated patient-reported outcome measures: Female Sexual Function Index and Female Sexual Distress Scale-Revised. Clinical and treatment data were collected by chart review. Vaginal dosimetry was abstracted from individual treatment plans, including: vaginal D2cm3 (minimum dose to hottest 2 cm3 of vagina), International Commission on Radiation Units and Measurements rectovaginal point (point dose 5 mm posterior to the applicator at the top of vagina), lateral point (point dose 5 mm lateral to the applicator at the top of vagina), point dose at posterior-inferior border of the symphysis (PIBS), and PIBS ± 2 cm (point dose ± 2 cm to PIBS). Vaginal Total Reference Air Kerma assessed dose loading within the vagina. Descriptive statistics summarized the data. Correlations were evaluated using logistic and linear regression analyses. Between August 2018 and April 2022, 73 patients were eligible. Median age was 49 (range, 25-81), median stage was IIB, 58% had vaginal involvement at diagnosis, and 33% had vaginal involvement at brachytherapy. Patients completed patient-reported outcome measures at a median of 19 months (range, 3-63) post treatment. Criteria for sexual dysfunction and distress were met in 73% (Female Sexual Function Index ≤ 26) and 55% (Female Sexual Distress Scale-Revised ≥ 11) of participants, respectively. Cumulative International Commission on Radiation Units and Measurements rectovaginal point dose >65 Gy (odds ratio, 5.04; 95% CI, 1.18-27.99; P = .040) and Vaginal Total Reference Air Kerma (odds ratio, 1.71; 95% CI, 1.04-3.04; P = .045) were associated with increased sexual distress on multivariable analysis. Sexual health following radiation therapy for cervical cancer is a multifactorial issue. This analysis identifies a novel association between brachytherapy dosimetry and sexual toxicity. Further attention to and evaluation of vaginal doses could improve our understanding of sexual health outcomes.
To examine the use of hypofractionation among underserved populations, with a focus on implications for policy. Using a 20% Medicare claims sample, we evaluated the receipt of hypofractionation, a short-course radiotherapy approach, among underserved versus non-underserved populations. Hypofractionation was defined based on cancer/site-specific guidelines and expert review. Underserved groups included racially/ethnically minoritized, rural, and low socioeconomic status patients. 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. This included breast, colorectal, lung, and prostate cancer. Log-binomial regressions were used to assess the association between underserved status and hypofractionation use, adjusting for patient-level, practice-level, and area-level characteristics. We analyzed 6,437 patients, finding 2,200 classified as underserved and 4,237 as not underserved. Overall, 52.5% of patients received hypofractionation and underserved populations were treated at similar rates to their non-underserved counterparts. We noted a few exceptions. Rural prostate cancer patients had a lower likelihood of receiving hypofractionation (RR 0.59, p = 0.005), while rural lung cancer patients had a higher likelihood of receiving hypofractionation (RR 1.14, p = 0.039). Hypofractionation was received at similar rates among underserved and non-underserved populations. Given existing disparities experienced by underserved cancer patients, 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 cancer patients.
The "FLASH effect", a phenomenon in which radiation-induced toxicity is diminished in healthy tissues when treated at ultra-high dose rates, has been demonstrated in several experimental models. We aim to evaluate the impact of split doses, the time interval between splits, and the effect of dose rate variations below and above the 40 Gy/s threshold. Mice received 16 Gy pelvic radiation with a scattering beam or a scanning beam. The conventional dose rate (CONV) was set at 0.5-1 Gy/s, while the FLASH effect was observed at dose rates ranging from 20 to 120 Gy/s. The mice were irradiated with a single dose or with a split-dose regime (1 or 2 splits) with pauses between treatments of either 30 seconds or 2 minutes. The endpoint was survival. The hazard ratio of a single irradiation in FLASH mode vs CONV was 0.31, confirming the presence of the FLASH effect. A split dose with a single 30-second or 2-minute pause reduced overall survival, with hazard ratios of 0.53 and 0.56, respectively. However, survival was still higher compared to CONV. Two 2-minute pauses were not significantly worse than one 2-minute pause. The lowest dose rate at which a FLASH effect was detected was 20 Gy/s; no benefit was observed for dose rates above 60 Gy/s. For the endpoint of 50% survival rate, the FLASH modification factor is 0.91 and 0.96 for irradiations without and with 1 or 2 pauses, respectively. The FLASH effect is attenuated by the introduction of a split-dose regimen. In the clinical implementation of FLASH, the benefit of multiple fields should be weighed against a reduction of the FLASH effect. For our endpoint, the minimum dose rate for FLASH is 20 Gy/s, while an increase from 60 Gy/s to 120 Gy/s is not beneficial.
Radiation therapy exerts direct cytotoxic effects on cancer cells, but also induces immunogenic responses in the tumor microenvironment (TME), eliciting both immune-stimulatory and immune-suppressive dynamics. These effects are influenced by fraction size, fractionation regimen, and timing of radiation therapy-immunotherapy co-administration. In this study, 2 opposing 2-fraction regimens were investigated, in which the same cumulative physical dose was applied to the tumor, but low- and high-dose fractions were administered in opposite order. Using 2 murine tumor models (MC38 and B16F10-Luc) implanted heterotopically, we investigated how dose sequencing affects the immune dynamics interplay in the TME and characterized the TME in response to low (6 Gy) and high (12 Gy) single doses of ionizing radiation and to 2 opposing fractionation regimens (6 + 12 Gy vs 12 + 6 Gy). Furthermore, we assessed the effect of the different radiation therapy regimens on tumor growth and survival and strategically combined the 2-fraction regimens with an immune checkpoint blockade. We demonstrated that the 2 opposing fractionation regimens generated distinct TMEs, depending on the sequence of low- and high-dose fractions. Although the 12 + 6-Gy regimen resulted in a TME enriched with CD8+ T cells with increased effector function, tumors treated with the 6 + 12-Gy regimen exhibited an enhanced proportion of suppressive CD4+ FOXP3+ regulatory T cells, thereby shaping ionizing radiation-induced antitumor immunity. By combining an immune checkpoint blockade with radiation therapy, we effectively counteracted the immune-suppressive effect, predominantly associated with the 6 + 12-Gy regimen. We demonstrated superior tumor control and a strengthened immunologic memory in response to this combinatorial approach and corroborated these findings in a secondary tumor model. The sequence of low and high radiation doses impacts the immunologic response and must be carefully considered for the delivery of heterogeneous fractionation schemes, particularly when combined with immunotherapy.
We performed an individual patient-level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT). A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of ≥79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT. The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8%) were World Health Organization grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2%). Three- and 5-year PFS rates were 62.8% (95% CI, 55.8%-69.0%) and 45.0% (95% CI, 37.3%-52.3%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4% vs 55.6%) and 5-year (65.8% vs 38.8%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9%) versus SD-RT (25 of 189; 13.2%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1% vs SD-RT 3.2%). DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.
Low-dose radiotherapy (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. 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 three-dimensional concept of the Clinical Target Volume (CTV). A standardized CT dataset ("homunculus") was used by all participants to ensure uniform anatomical reference for target volume delineation. 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 three-dimensional 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. This international consensus statement provides practical guidance for a standardized three-dimensional target volume definition in the radiotherapy 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.
Pelvic radiotherapy is commonly incorporated in the treatment of locally-advanced rectal cancer to reduce the risk of locoregional recurrence, but can be associated with substantial acute toxicity and long-term morbidity. However, treatment may be personalized for selective use of radiotherapy in a subset of patients identified to be at low to intermediate risk of locoregional recurrence following resection. This multi-specialty-led committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and colorectal surgery. Using the Population, Intervention, Comparator, Outcome, Timing and Study Design (PICOTS) framework, evidence regarding treatment outcomes was assessed using Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Eligible studies included prospective and retrospective (n ≥ 50) studies published between 1/1/2005 - 6/24/2025 from Embase, Medline and PubMed databases. Study type and quality were assessed. Well-established RAND corportaion/University of California Los Angeles (RAND-UCLA) consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options. Of the 110 articles identified using the search strategy, 35 were selected that met all inclusion criteria. Of the 35 references used as evidence, 35 are categorized as therapeutic including 14 well-designed studies (Phase II randomized and Phase III), 12 moderately well-designed studies that account for most common biases (matched cohort and Phase II studies), 7 studies with design limitations (retrospective reviews), and 3 meta-analyses. Variant cases were developed as examples to illustrate practical applications of consensus recommendations for when RT can be safely omitted. A treatment algorithm is also provided to assist with treatment decisions when considering selective use of pelvic RT.
Definitive stereotactic body radiation therapy (SBRT) for inoperable pancreatic ductal adenocarcinoma (PDAC) is often delivered with a nonablative dose to gross tumor alone despite high rates of locoregional failure (LRF). The purpose of this study was to characterize patterns of failure after definitive ablative SBRT and evaluate the impact of clinical target volume (CTV) design. We performed a retrospective cohort study of nonmetastatic PDAC treated with definitive ablative SBRT on a 0.35 Tesla MR-Linac between 2018-2024. Patients who had surgery were excluded. The median prescribed gross tumor volume and CTV doses were 50 Gy and 33 Gy in 5 fractions, respectively. CTV coverage evolved from no CTV or limited perivascular coverage to larger anatomically derived volumes eventually including the "triangle volume." The first diagnostic scan showing LRF was registered to the simulation scan on which the recurrence was contoured. LRFs were classified as in-field, marginal, or out-of-field. Among 121 consecutive patients, 87.6% received induction chemotherapy, and 92.6% were treated with a CTV. Median follow-up after SBRT was 12.0 months. LRF occurred in 17 patients (14.0%) at a median of 14.3 months and no LRF was observed in patients treated to the "triangle volume." In-field failures were rare (2.5%) as were marginal (6.6%) and out-of-field (5.0%) failures. LRF involved the primary tumor (n = 5; 29.4%), paraaortic lymph nodes (n = 4; 23.5%), porta hepatis (n = 4; 23.5%), superior mesenteric artery (n = 3; 17.6%), or celiac artery (n = 1; 5.9%). Larger CTV size was associated with a nonstatistically significant increase in acute grade 1 to 2 nausea. This is the first study to characterize patterns of LRF following induction chemotherapy and definitive ablative SBRT for inoperable PDAC. Our findings suggest that routine use of an anatomically derived CTV should be considered including the "triangle volume."
Clinical control of oral squamous cell carcinoma (OSCC) is constrained by heterogeneous radiosensitivity driven by divergent DNA damage response programs. The architecture and functional contribution of alternative end joining (Alt-EJ), an error-prone DNA double-strand break (DSB) repair pathway frequently upregulated in cancer, to radiation resistance remains poorly defined. We profiled microRNAs in radioresistant OSCC clones and performed multiomic integration across an institutional OSCC cohort, an external OSCC cohort from the Gene Expression Omnibus, The Cancer Genome Atlas pan-cancer tumors, and cell lines characterized by Sanger Genomics of Drug Sensitivity in Cancer to infer DNA damage response characteristics, genomic scar features, drug sensitivity, and radiation therapy outcomes. DSB repair capacity and pathway usage were validated using functional assays, including Alt-EJ reporters and droplet digital PCR quantification of microhomology-mediated repair events. Core Alt-EJ effectors such as PARP1 and POLQ were perturbed genetically and pharmacologically. Therapeutic efficacy of PARP or POLQ inhibition with or without irradiation was tested in a syngeneic OSCC model, followed by bulk tumor transcriptomics to assess pathway engagement. Upregulation of miR-21-5p was not only selectively detected in radioresistant OSCC, but also modulated radiosensitivity in vitro and in vivo, and was associated with inferior postradiation therapy survival. A calibrated miR-21-5p target-gene signature tracked Alt-EJ activity across patient and mouse tumors and cancer cell lines, correlated with microhomology-mediated indels and broader genomic scarring, and predicted sensitivity to clinically available PARP inhibitors. Functionally, enforced miR-21-5p expression increased Alt-EJ usage and accelerated DSB repair, whereas inhibition or depletion of key Alt-EJ effectors reduced repair efficiency and restored radiosensitivity. In vivo, Alt-EJ targeting with PARP or POLQ inhibitor abrogated miR-21-5p-driven radiation resistance; transcriptomic profiling supported suppression of Alt-EJ programs as the operative mechanism. These findings establish a mechanistic link between miR-21-5p activity and Alt-EJ dependence, provide a clinically deployable signature to identify Alt-EJ-dependent OSCC, and support rational combinations of Alt-EJ targeting agents with radiation therapy to overcome treatment failure and advance precision radiation oncology.
Palliative radiotherapy (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. 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, non-evaluable (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). 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 < 0.0001). Forty-seven episodes (15.2%) were classified as non-evaluable. 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. 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 non-evaluation from clinical infeasibility, improving transparency in the interpretation of real-world palliative RT outcomes.
the CYGNUS study aims to assess both toxicity and efficacy of stereotactic body radiotherapy (SBRT) performed as salvage approach for pelvic nodal metachronous oligorecurrent (PNMOR) hormone-sensitive prostate cancer (PCa), in previously irradiated territory. Inclusion criteria were histologically history of proven PCa, locally treated with a radical intent and a biochemical relapse as defined by the European Association of Urology guidelines. All patients had a radiological suspicion of PNMOR, defined as a recurrence occurring in pelvic nodal areas with up to 5 suspect lymph nodes. Reirradiation was defined according to the ESTRO-EORTC consensus on re-irradiation as an irradiation with a geometrical overlap with a previous course of RT. A total of 155 re-irradiation among 150 patients relapsing on 192 nodal sites were retrospectively included, from 13 French centers. The majority of patients (80.7%) received radical prostatectomy as primary treatment. After a median follow-up of 30.5 months, late grade 2 and grade 3 GI and GU toxicity occurred in 1.9%, 0% and 7.1% and 2.6% of the cases, respectively. The 2-year radiological progression-free survival (rPFS) reached respectively 44.6% (95% CI: 36.2% - 55%).. The 2-year androgen deprivation therapy-free survival (ADT-FS) reached 52.6% (95% CI: 42% - 65.9%). Previous ADT prescription was predictive in multivariable analysis of both rPFS (HR:2.02, 95%CI: 1.25-3.26, p=0.004) and ADT-FS (HR:2.49, 95%CI: 1.28-4.72, p=0.006). A PSA doubling time <5months correlated with a shorter ADT-FS (AUC 0.629, p= 0.014). The CYGNUS retrospective study suggests that reirradiation with SBRT for PNMOR is associated with a low rate of toxicity. However, further data with plan summation and longer follow-up are needed to confirm these findings.
The inconsistent delineation style of clinical target volume (CTV) in postoperative pelvic radiotherapy of endometrial carcinoma across different centers is challenging for deep learning-based segmentation due to different definitions of internal target areas. This study aims to develop an effective method to address multi-institutional variations in CTV delineation, even under the constraints of scarce data availability. A total of 207 simulated CT cases from endometrial cancer patients across five centers were retrospectively collected. Within each center, the data were divided into support, query, and test sets. Each center was sequentially designated as the target center for fine-tuning and testing, while the remaining four centers were used for model training to validate the superiority of the proposed method. In addition, 26 cases from an external center were used exclusively for fine-tuning and testing. Radiomics features were extracted to analyze the differences in CTV delineation and image among the centers. A Random Forest Classifier (RFC) was trained to identify the most important radiomics features. Using these features as guidance, a Model-Agnostic Meta-Learning (MAML) strategy was applied to pre-train a 3D U-Net model (MAML-r), which was subsequently fine-tuned on each target center's data. The performance of the proposed MAML-r method was compared against direct 3D U-Net training and transfer learning approaches. Evaluation metrics included the Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD95), and Average Symmetric Surface Distance (ASSD), supplemented by qualitative assessment from clinical experts using a four-point scoring system. The 8 most important features were identified from a total of 107 radiomics features, which showed significant differences across centers (p < 0.01). The MAML-r model yielded meaningful results, achieving a DSC a mean DSC of 0.818 ± 0.058, a mean HD95 of 9.314 ± 3.648 mm, and a mean ASSD of 2.772 ± 1.090 mm. It also earned an average blinded expert evaluation score of 3.24, significantly outperforming all other models. Notably, improved performance was observed on the external test cohort, with corresponding values of 0.886 ± 0.012, 5.203 ± 1.435 mm, and 1.512 ± 0.334 mm, respectively. Furthermore, the MAML-r model achieved the shortest CTV modification time of 3.8±1.2 minutes. Given the variations in CTV contouring styles across different centers with limited samples, the MAML-r model demonstrates superior performance and adaptability compared to other models. This study introduces a novel radiomics-guided MAML framework for few-shot, multi-centric CTV segmentation tasks in postoperative pelvic radiotherapy for endometrial carcinoma, significantly mitigating performance degradation caused by inter-institutional delineation style variations and data scarcity. The proposed approach thus offers a promising solution to these persistent clinical challenges.
There is a strong desire to exploit daily MR-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. We analysed T2-weighted and diffusion MRL data of prostate cancer patients undergoing hypofractionated radiation treatment. Next to standard mask-based analyses, we introduce exploratory analyses using classic 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 T2w signal changes in pelvic bone tissue, chosen for its wide range of dose values received (0-26 Gy; 0-47 Gy EQD2). Mask-based analyses of the MRI data of all fractions reveal T2w signal decreases for prostate tissue whereas the GTV signal stays more constant throughout the treatment. The diffusion coefficient of the prostate gland remains constant while the GTV shows an increase. Prostate volume increases by 10% in the first week after which it slowly decreases again. The fMRI-inspired analysis shows prostate T2w 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 0-1 Gy (0.55 Gy EQD2). Exploratory fMRI-inspired analyses were able to demonstrate many temporal, non-linear 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 behaviour with a sudden dose-response starting at 1 Gy.
Radiation-induced lymphopenia (RIL) 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 multi-fraction thoracic FLASH RT on lymphocyte preservation, apoptosis, and immunosuppressive signaling in mice. We compared the immunological impact of thoracic FLASH RT and CONV RT in C57BL/6 mice using single-fraction (17 Gy) and multi-fraction (2 Gy × 5) regimens using the Mobetron (IntraOp). Longitudinal blood sampling was performed at multiple time-points post-irradiation 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 (Tregs) and PD-1/PD-L1 expression. Mechanistic studies included immunofluorescence and Western blot analyses of splenic tissues to evaluate Chk1 and STAT3 signaling pathways. In single-fraction RT, FLASH significantly reduced lung and heart fibrosis (p < 0.0001) 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 multi-fraction regimens. Conversely, CONV RT induced long-lasting increases in Tregs and sustained PD-1 and PD-L1 expression on T- and B-cells at 2- and 5-months post-irradiation 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. FLASH RT mitigates RIL, 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.
Stereotactic body radiation therapy (SBRT) provides excellent local control for localized prostate cancer (PC); however, systemic relapse remains the primary cause of mortality 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 GPNMB⁺ myeloid-derived suppressor cells (MDSCs) as a dominant systemic response to clinical SBRT and demonstrate a tractable strategy to counter it. 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 patient PBMCs. For further characterization, we used a syngeneic PC RM-9 tumor model. RT-PCR and luciferase assays determined the mechanism observed. We observed a selective and reproducible expansion of GPNMB⁺ MDSCs accompanied by enhanced T-cell suppression. GPNMB blockade in patient's PBMCs 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 SDC4 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 PD-L1 blockade. Transcriptomic and mechanistic analyses identified MITF as a key regulator of radiation-induced GPNMB expression. Together, these findings define an actionable RT → MDSC → GPNMB myeloid checkpoint that suppresses T-cell immunity in prostate cancer 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 prostate cancer.
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. 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. 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. 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.
Radiation therapy (RT) following breast-conserving surgery reduces the risk of recurrence for early-stage breast cancer. A subset of patients with favorable clinical and pathologic characteristics can safely omit RT with a modest increase in recurrences, yet without survival implications. We sought to evaluate whether molecular risk profiling among such patients could further stratify them into (1) a higher-risk subgroup that may be inappropriate for RT omission and (2) an exceedingly favorable subgroup that might more strongly consider RT omission. Using a prospectively maintained institutional database, we evaluated patients aged ≥65 years who underwent breast-conserving surgery for early-stage, estrogen receptor-positive breast cancer (ie, patients putatively eligible for RT omission). Patients were stratified by clinicopathologic features and Oncotype DX Recurrence Score (RS; ≤25 vs >25) and were evaluated for oncologic outcomes and survival by receipt of RT. The overall cohort comprised 1587 patients: 92% had RS ≤25 (n = 1455) and 8% had RS >25 (n = 132). With a median follow-up of 74.4 months, the cumulative incidence of local recurrence was low throughout and did not significantly differ between those with RS ≤25 vs >25 (6-year rate 1.9% vs 0.8%; P = .5). Among those who did not undergo RT (n = 350), patients with RS >25 (n = 19) did not have a significantly higher incidence of local recurrence than patients with RS ≤25 (6-year rate 5.6% vs 4.2%; P = .5). Among patients ≥65 years of age who underwent breast-conserving surgery for early-stage estrogen receptor-positive breast cancer, Oncotype DX RS did not further refine recurrence risk estimates for RT decision-making beyond the findings of landmark RT omission trials. Although the number of patients with Oncotype DX RS >25 who omitted RT was limited in this study, this subgroup did not exhibit a significantly higher risk than their low-molecular-risk counterparts, suggesting that risk score need not necessarily disqualify select patients who seek to forgo adjuvant RT. Prospective analyses with larger sample sizes will further elucidate the role of molecular assays in guiding RT decision-making across risk strata.
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.
To assess the impact of defacing-based deidentification techniques on reidentification risk and data utility across multimodal imaging in radiation therapy. We applied 4 defacing techniques: biometric_mask, quickshear, mri_reface, and Carina's deidentifier, to imaging from 88 brain patients (magnetic resonance imaging, computed tomography [CT], and RTDose) and 97 head and neck patients (positron emission tomography, CT, and RTDose) in The Cancer Imaging Archive. Reidentification risk was assessed using ArcFace, a deep learning-based facial recognition model, by measuring cosine similarity scores and conducting receiver operating characteristic analysis to distinguish between original and defaced images. Data integrity was evaluated by statistically comparing the volume and image intensity changes between the original and defaced images across 9 critical organs and gross tumor volume. Quickshear provides the highest privacy protection, achieving the lowest area under the curve across imaging modalities (area under the curve, 0.61-0.74), followed by Carina (0.59-0.80). Mri_reface showed moderate protection (0.70-0.91), whereas biometric_mask offered the least (0.76-0.94). Carina preserved structure volumes, and mri_reface produced minor volumetric changes in the eyes (5%) and lens (9%). In contrast, biometric_mask substantially affected the mandible (39%) and oral cavity (69%), whereas quickshear significantly altered multiple structures (10.0%-86.6%). Median changes in mean CT intensity after defacing were -48.3% (interquartile range [IQR], -65.9% to -33.9%) with biometric_mask and -77.7% (IQR, -89.4% to -51.7%) with quickshear in the oral cavity. For eyes, Carina and mri_reface produced changes of +24.5% (IQR, 11.6% to 38.2%) and +54.9% (IQR, 16.2% to 82.3%), respectively. In the brain data set, biometric_mask and quickshear decreased oral cavity Dmean by 0.72 Gy (IQR, 0.33 Gy to 0.89 Gy) and 1.61 Gy (IQR, 0.72 Gy to 2.12 Gy), respectively. Carina and mri_reface reduced eyes Dmax by 2.11 Gy (IQR, 0.00 Gy to 3.39 Gy) and 1.05 Gy (IQR, 0.21 Gy to 1.16 Gy), respectively. A similar trend was observed in the head and neck data set with larger deviations. Carina's deidentifier and mri_reface showed favorable privacy-utility trade-offs relative to facial removal; the optimal choice may vary by application priorities.