International Journal of Radiation Oncology Biology Physics最新文献

{"title":"The Dilemma of Choice: Options for Nonoperable Hepatocellular Carcinoma Management","authors":"Natnaiel M. Dubale BSc , Michael Lock MD","doi":"10.1016/j.ijrobp.2025.05.092","DOIUrl":"10.1016/j.ijrobp.2025.05.092","url":null,"abstract":"","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Pages 917-918"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Treating Fields (TTFields) after Stereotactic Radiosurgery (SRS) for Brain Metastases from Non-Small Cell Lung Cancer (NSCLC BM): Final Results of The Phase 3 METIS Trial","authors":"V. Gondi ,&nbsp;M. Ahluwalia ,&nbsp;D. Roberge ,&nbsp;R. Ilic ,&nbsp;T.T.W. Sio ,&nbsp;D.M. Trifiletti ,&nbsp;T.M. Muanz ,&nbsp;A.M. Krpan ,&nbsp;Z. Zhu ,&nbsp;N.R. Ramakrishna ,&nbsp;J.B. Fiveash ,&nbsp;P.B. Metellus ,&nbsp;C.J. Wang ,&nbsp;J. Jacob ,&nbsp;J. Yu ,&nbsp;C.F. Freyschlag ,&nbsp;T. Csőszi ,&nbsp;P.D. Brown ,&nbsp;M. Harat ,&nbsp;M.P. Mehta","doi":"10.1016/j.ijrobp.2025.08.027","DOIUrl":"10.1016/j.ijrobp.2025.08.027","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Local therapy for NSCLC BM includes resection, SRS and whole brain radiotherapy (WBRT). Intracranial progression after resection or SRS is more frequent than with WBRT, but WBRT causes more neurotoxicity and neurocognitive decline. Delaying intracranial failure while preserving neurocognition is an unmet need. TTFields, electric fields delivered via scalp-placed arrays that disrupt cancer cell division, have demonstrated efficacy in glioblastoma, NSCLC and pancreatic cancer.</div></div><div><h3>Materials/Methods</h3><div>In the METIS trial (NCT02831959), adults with 1–10 newly diagnosed NSCLC BM suitable for SRS and receiving optimal therapy for extracranial disease were eligible. Prior WBRT, presence of known druggable mutations, single operable or recurrent BM were exclusion criteria. Patients (pts) were randomized 1:1 to SRS followed by TTFields therapy (150 kHz) or SRS alone. A blinded independent radiology review committee assessed radiographic progression. The primary endpoint of time to intracranial progression (TTIP, RANO-BM) was analyzed using cumulative incidence competing risk and Fine-Gray test to determine a difference. Secondary endpoints included time to distant progression (TTDP), neurocognitive function, overall survival (OS), quality of life (QoL) and safety.</div></div><div><h3>Results</h3><div>The trial enrolled 298 pts (TTFields after SRS vs SRS): median age 63 vs 64 years; KPS ≥80 81% vs 91%; median time from NSCLC diagnosis 1.5 vs 2.2 months; adenocarcinoma 75% vs 79%. Median duration of TTFields therapy was 15.7 (0.1–193.1) weeks; median monthly usage was 67.1% (0.8–96.7%). Time to first intracranial progression from SRS was significantly delayed with TTFields therapy (HR 0.72, 95% CI 0.53–0.98; p=0.044). Intracranial progression rates at months 2, 6, 12, and 24 were 13.6% vs 22.1% (p=0.034), 33.7% vs 46.4% (p=0.018), 46.9% vs 59.4% (p=0.023), and 53.6% vs 65.2% (p=0.031; post hoc). In the 118 pts receiving immune checkpoint inhibitors (ICI) for their primary disease, TTIP benefit was more pronounced (HR 0.63, 95% CI 0.39–1.0; Cox p=0.049; Fine-Gray test p=0.055; post-hoc). While no difference in TTDP was observed overall (HR 0.76, 95% CI 0.51-1.12, p=0.165; post-hoc), in pts receiving ICI, TTFields therapy delayed TTDP compared with SRS alone (HR 0.41, 95% CI 0.21–0.81; p=0.009; post-hoc). Time to neurocognitive failure, OS and radiological response rate did not differ significantly. Device-related AEs were mainly grade ≤2 skin events. TTFields did not cause QoL deterioration, and improvements in deterioration-free survival and time to deterioration of global health status, physical functioning and fatigue were observed (post-hoc).</div></div><div><h3>Conclusion</h3><div>By significantly prolonging time to intracranial progression, without deteriorating QoL or cognitive function, TTFields therapy after SRS is a potential new treatment option for pts with NSCLC BM. .</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Pages 1196-1197"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline and Time-Dependent Predictors of Cognitive Decline for Brain Metastasis Patients Treated with Radiotherapy– A Secondary Analysis of the ATHENA Trial","authors":"H.K. Perlow ,&nbsp;Y. Sun ,&nbsp;E. Dawson ,&nbsp;K. Dibs ,&nbsp;A. Ritter ,&nbsp;D. Boulter ,&nbsp;A. Nalin ,&nbsp;R. Singh ,&nbsp;S. Beyer ,&nbsp;S. Zhu ,&nbsp;D.M. Blakaj ,&nbsp;J.C. Grecula ,&nbsp;R. Raval ,&nbsp;S. Vazquez ,&nbsp;S. Whitman ,&nbsp;C. Presley ,&nbsp;C. Pillainayagam ,&nbsp;P. Giglio ,&nbsp;E.M. Thomas ,&nbsp;J.D. Palmer","doi":"10.1016/j.ijrobp.2025.08.037","DOIUrl":"10.1016/j.ijrobp.2025.08.037","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>The extent to which radiotherapy contributes to cognitive decline, versus baseline characteristics and subsequent events such as systemic therapy administration, intracranial progression, and systemic progression, is unclear. This secondary analysis of a Phase 2 Randomized Controlled Trial (NCT05503251) aimed to evaluate the impact of baseline and time-dependent clinical and treatment characteristics on cognitive decline.</div></div><div><h3>Materials/Methods</h3><div>This is a planned secondary analysis of a clinical trial in which patients with brain metastases were randomized 1:1 to either brain radiation alone or brain radiation with neuropsychology evaluation and intervention. Previous endpoint analyses showed no difference in cognitive decline between control and intervention arm. The following baseline characteristics were collected: type of radiation (stereotactic radiosurgery versus IMRT WBRT), Karnofsky Performance Status (KPS), sex, education level, primary tumor histology, age, brain metastases at time of cancer diagnosis, extracranial disease control, extracranial metastases, number of brain metastases, brain tumor volume, previous brain radiation, receipt of any systemic therapy, and receipt of chemotherapy. Receipt of systemic therapy after trial enrollment, intracranial disease status, systemic disease status, and survival were evaluated for at least 12 months after trial enrollment. Cognition was measured by Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association Test, and Trail Making Test A/B. Cognitive decline defined as a decline on at least one assessment using the reliable change index. Analyses were performed using Gray’s test and Fine-Gray regression model.</div></div><div><h3>Results</h3><div>Between August 2022 and June 2024, 110 patients were enrolled on the ATHENA Trial and eligible for analysis. On univariable analysis (UVA), only KPS &gt;70 vs. ≤ 70 (p = 0.044) was predictive of cognitive preservation. Increased brain tumor volume (p=0.044), intracranial progression (p=0.034), and systemic progression (p = 0.005) were predictive of cognitive decline. On multivariable analysis of the four significant variables on UVA, KPS &gt; 70 retained an association with cognitive preservation (p=0.011) and systemic progression retained an association with cognitive decline (p=0.026).</div></div><div><h3>Conclusion</h3><div>For brain metastases patients treated with radiotherapy, baseline performance status and systemic progression may be more predictive of cognitive decline than traditional implicating factors such as type of radiation, age, number of brain metastases, or systemic therapy administration. Cognitive intervention strategies for any patient with poor performance status or progressing systemic disease may be warranted. These findings will be further investigated with multi-institutional ATHENA Consortium data.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Pages 1202-1203"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Chemotherapy with Trastuzumab with or without Concurrent Radiotherapy in HER2-Positive Inoperable Locally Advanced Breast Cancer: A Phase 2 Randomized Trial (NEOTRAC)","authors":"P. Iyer ,&nbsp;A. Krishnamurthy ,&nbsp;S. Velusamy ,&nbsp;S. Sundersingh ,&nbsp;G. Selvarajan ,&nbsp;S. Rajaram ,&nbsp;P. Venkatraman ,&nbsp;V. Radhakrishnan","doi":"10.1016/j.ijrobp.2025.08.036","DOIUrl":"10.1016/j.ijrobp.2025.08.036","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;The role of neoadjuvant concurrent chemoradiotherapy (NACCRT) with anti-HER2 therapy remains unexplored. We report the first phase 2 randomized controlled trial (RCT) evaluating whether adding NACCRT and trastuzumab improves pathological complete response (pCR) in HER2-positive inoperable locally advanced breast cancer (LABC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;Patients with newly diagnosed HER2-Positive inoperable LABC were randomized in a 1:1 ratio to receive either NACT with trastuzumab (Arm A) or NACCRT and trastuzumab (Arm B). Both arms received four cycles of Adriamycin and Cyclophosphamide (q 3 weekly), followed by four cycles of Paclitaxel (q 3 weekly) and nine weekly cycles of Trastuzumab. In Arm B, patients received concurrent radiotherapy (RT) to a total dose of 46 Gy to the breast and nodal areas along with paclitaxel and trastuzumab, followed by mastectomy. In contrast, patients in Arm A received postmastectomy RT to a total dose of 50 Gy after NACT and surgery. Adjuvant trastuzumab (q 3 weekly) was continued for one year in both arms. Primary endpoint was pCR while secondary endpoints included survival, toxicity, and treatment duration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among 118 enrolled patients (Arm A: 62; Arm B: 56), 113 underwent surgery (Arm A: 58; Arm B: 55). Five patients (Arm A: 4; Arm B: 1) with complete clinical response (cCR) declined surgery. The median age was 50 years (range: 24–65), and all had stage III disease (IIIA: 40/118, [33.9%]; IIIB: 68/118 [57.6%]; IIIC: 10/118, [8.5%]). pCR rates were 46.6% (27/58) in Arm A versus 50.9% (28/55) in Arm B (P= 0.64), with no differences by subgroups (hormone receptor status, menopausal status, tumor size and stage grouping). At a median follow-up of 27 months, survival outcomes were similar. Event-free survival (EFS) was 81.0% (95% CI: 66.2–89.8) in Arm A versus 81.9% (65.2–91.1) in Arm B (P = 0.79). Overall survival (OS) was 93.0% (80.1–97.9) versus 95.1% (81.3–98.8) (P = 0.88) in Arms A and B respectively. NACCRT significantly reduced treatment duration (median 189 vs. 255 days, P &lt; 0.00001). Surgical wound morbidity occurred in 6.9% (4/58) of Arm A versus 16.4% (9/55) of Arm B (P = 0.15). Grade 3 radiation dermatitis of 5.5% (3/55) and neutropenia 3.6% (2/55) were observed only in Arm B. No cardiac toxicity occurred. Among cCR patients declining surgery, 1/4 in Arm A progressed, while all others (3/4 Arm A, 1/1 Arm B) remained disease-free.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;To our knowledge, this is the first RCT of NACCRT with trastuzumab. While pCR was higher with NACCRT, the difference was not significant. NACCRT was well tolerated, showed no added cardiac toxicity, and significantly reduced treatment duration, potentially lowering hospital visits and income loss. It may be a feasible option for patients seeking shorter, effective treatment. Further studies are warranted to explore whether the benefit of shor","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Page 1202"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal-Seeking P2R Trial of Proton or IMRT Dose Intensification in GBM: NRG-BN001","authors":"M.P. Mehta ,&nbsp;S. Pugh ,&nbsp;A. Mahajan ,&nbsp;H.A. Shih ,&nbsp;C. Tsien ,&nbsp;T. Chenevert ,&nbsp;M. Gilbert ,&nbsp;A. Omuro ,&nbsp;K. Aldape ,&nbsp;B.K.K. Teo ,&nbsp;Y. Cao ,&nbsp;A. Srinivasan ,&nbsp;O.H. Khan ,&nbsp;J. Huang ,&nbsp;P.D. Brown ,&nbsp;R. Kotecha ,&nbsp;P. Vempati ,&nbsp;D.N. Yeboa ,&nbsp;M. Won ,&nbsp;V. Gondi","doi":"10.1016/j.ijrobp.2025.08.068","DOIUrl":"10.1016/j.ijrobp.2025.08.068","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose/Objective(s)&lt;/h3&gt;&lt;div&gt;RT dose-intensification in GBM demonstrates survival (OS) improvement, up to 60 Gy; escalation &gt;60 Gy in the pre-temozolomide (TMZ) era failed to lengthen OS. Non-randomized concomitant RT TMZ trials have established simultaneous integrated boost (SIB) intensification to 75 Gy as safe and potentially more effective. Further, lymphopenia in GBM is strongly associated with reduced OS; significant associations between lymphopenia and volume of brain irradiated are established; level 1 evidence demonstrates less lymphopenia with protons. In this signal-seeking Phase 2 randomized trial we tested the dual hypothesis of SIB intensification (DI) to 75 Gy with photon therapy (previously presented), and with proton therapy with the expectation of benefit from less lymphopenia. Here we present the proton cohort results.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials/Methods&lt;/h3&gt;&lt;div&gt;Patients with newly diagnosed GBM, KPS≥70, with ≤5cm residual tumor/cavity, after central pathology confirmation and central MGMT analysis were stratified by RPA class and MGMT status and randomized 1:2 at pre-declared photon centers to 60 Gy/30 fxs with photons or 75 Gy/30 fxs with proton therapy (DI), providing separate and independent SOC controls for photon and proton cohorts. Standard concomitant and adjuvant TMZ usage was included. For the 193-patient proton cohort, there was 80% power to detect a hazard ratio (HR) = 0.72 (median OS D 16.0 to 22.2 months), with a one-sided α at 0.15, 1 interim futility analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Between October 2014 and May 2022, the proton cohort randomized 193 patients. Patients were balanced between arms for pretreatment characteristics (the proton DI arm had numerically more unmethylated GBMs, more patients with lower KPS, and fewer with gross-totally resected tumors versus the 60 Gy comparator). No statistically significant between arms differences in high grade toxicities (all) were observed; specifically, ≥G3 lymphopenia and ≥G4 neurologic toxicity rates for SOC vs. proton DI were 23.4 vs 17.1, and 1.8% vs 5%. The proton 75 Gy arm demonstrated improved OS (HR= 0.81, 70% CI 0.67-0.98, p =0.11) and remained significant when correcting for MGMT methylation status and RPA class. The absolute survival improvement in favor of 75 Gy proton arm at 2 and 3 years was 6.8% (43.1 vs 49.9%) and 4.6% (25.4 vs 30%), with median OS of 22.8 (20-28.6) vs 22 (15.8-27.8) months. As expected, OS was superior for both MGMT methylated as well as for lower RPA class patients, and without significant interaction between treatment arm and either MGMT status or RPA. Results didn’t meet criteria for comparing 75 Gy protons vs 75 Gy photons.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This signal-seeking P2R multicenter NRG Oncology trial did not demonstrate OS improvement with 75 Gy photon SIB (previously reported) but met the pre-specified statistical hypothesis for improved OS for the proton 75 Gy cohort, providing th","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Page 1204"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen Deprivation Therapy (ADT) and High Dose Definitive Radiotherapy (RT) ± Whole Pelvic RT in Patients with Unfavorable Intermediate or Favorable High-Risk Prostate Cancer: Early Results of a Phase III Randomized Controlled Trial","authors":"M. Roach III ,&nbsp;T.G. Karrison ,&nbsp;H.T. Chung ,&nbsp;A.J. Chang ,&nbsp;L.G. Gomella ,&nbsp;I.C.J. Hsu ,&nbsp;G. Morton ,&nbsp;R.E. Wallace ,&nbsp;B. Movsas ,&nbsp;D.W. Bruner ,&nbsp;A.P. Dicker ,&nbsp;D.E. Citrin ,&nbsp;I. Kauffman ,&nbsp;J.M. Michalski ,&nbsp;E. Vigneault ,&nbsp;M.A. Papagikos ,&nbsp;D.E. Spratt ,&nbsp;A. Jani ,&nbsp;T. Johnson ,&nbsp;H.M. Sandler","doi":"10.1016/j.ijrobp.2025.08.029","DOIUrl":"10.1016/j.ijrobp.2025.08.029","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Assess whether prophylactic whole pelvic radiotherapy (WPRT) improves overall survival (OS) compared to prostate only dose escalated radiotherapy (PORT) in patients with protocol defined unfavorable intermediate risk (UIR) or favorable high risk (FHR) prostate cancer (PC).</div></div><div><h3>Materials/Methods</h3><div>Eligible patients had localized prostate cancer with an estimated risk of lymph node involvement of ≥ 15% (Roach equation), and UIR or FHR (PSA &lt;50 ng/ml clinical T1-2b, i.e., no T3’s) PC and a Zubrod of 0 or 1. Patients were stratified by the risk group, RT boost: brachytherapy (BT) vs intensity modulated RT (IMRT) to 79.2 Gy, and duration of ADT (4 to 6 vs 32 months) and randomized to PORT or WPRT (superior border at the L4-5 interspace), arms 1, and 2 respectively, with the primary endpoint OS. Staging and treatment were based on conventional imaging.</div></div><div><h3>Results</h3><div>From July 2011, thru June 24, 2019, 2473 (UIR=1130; FHR=1343) eligible and evaluable patients were accrued (median age 69 years). Approximately 30% of patients received long term ADT, 21% received a BT boost, 16% had a PSA &gt; 20ng/mL, while 98% had a Gleason score of 7-10. At the planned interim analysis, WPRT did not improve OS, therefore the Data Safety Monitoring Committee released the data, with a median follow-up was 7.3 years (IQR 6.1-9.2), and 64 patients followed beyond 12 years. The 10-year OS was 68% (hazard ratio [HR]=1.01, 95% CI: 0.85-1.20, <em>one-sided</em> p=0.54), and PC specific survival (PCS) 98%, on both arms. The cumulative incidence of biochemical failure (BF) by the Phoenix definition at 10 years was 17% and 13% for arms 1 and 2, respectively (cause-specific HR=0.82, 95% CI: 0.65-1.03, one-sided p=0.045), but there was no difference in the risk of distant metastases (cause-specific HR=1.05, 95% CI: 0.73-1.50, one-sided p=0.60). The maximum gastrointestinal (GI) grade 2 (CTCAE version 4) adverse event rate was 14.7% on the PORT arm vs 18.7% on the WPRT arm (p=0.0035, one-sided). However, there was no difference in grade ≥3 GI adverse events being 3.4% on the PORT vs 3.3% on the WPRT arm. The reported rate of grade 2 and ≥ 3 urinary frequency was 24.8 and 0.5% on the PORT arm respectively, vs 26.5 and 0.7% on the WPRT arm.</div></div><div><h3>Conclusion</h3><div>At 10 years, WPRT did not improve OS in men with UIR or FHR PC. However, the follow-up is relatively short, with most cancer related deaths expected beyond 10 years. Additional follow-up is warranted to determine whether the early trends in BF ultimately translate into differences in OS or metastases. The high PCS rate and relatively low morbidity (by physician report) confirms that ADT + PORT appears to represent an excellent treatment option for men with UIR or FHR PC. Future studies incorporating biomarkers may help us determine whether there are subsets of patients who would benefit from WPRT.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Page 1198"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Too Big to Burn? Just Beam It!","authors":"Banu Atalar MD,&nbsp;Neris Dincer MD","doi":"10.1016/j.ijrobp.2025.06.3879","DOIUrl":"10.1016/j.ijrobp.2025.06.3879","url":null,"abstract":"","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Page 921"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-Compassion and Help Seeking in Medicine","authors":"Marie Soller MD","doi":"10.1016/j.ijrobp.2025.04.043","DOIUrl":"10.1016/j.ijrobp.2025.04.043","url":null,"abstract":"","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"123 4","pages":"Pages 929-931"},"PeriodicalIF":6.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiobiology and Radioresistance in High-Dose Radiosurgery for Brain Tumors: A Hypothesis-Generating Study Using an Intracranial Glioma Mouse Model.","authors":"Anastasia Janas, Carolin Senger, Kiril Krantchev, Susan Brandenburg, Wenying Zhang, Anne Kluge, Sanaria Al-Rubaiey, Jan Bukatz, Chiara Eitner, Melina Nieminen-Kelhä, Philipp Boehm-Sturm, Ingeborg Tinhofer, Daniel Zips, Peter Vajkoczy, Gueliz Acker","doi":"10.1016/j.ijrobp.2025.09.061","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.09.061","url":null,"abstract":"<p><strong>Introduction: </strong>Stereotactic radiosurgery (SRS) is a precise, non-invasive treatment for brain tumors, yet underlying radiobiological mechanisms remain unclear. This study explored long-term dose-dependent tumor response to high-dose SRS in a murine glioma model, focusing on tumor-associated macrophages (TAMs) as key regulators of tumor microenvironment and immune modulation.</p><p><strong>Methods: </strong>Using the intracranial GL261-glioma mouse model, single-dose SRS was administered at either 20-Gy (clinically prescribed dose) or 40-Gy as a dose-escalation approach (n=24/dose). Tumor response was assessed longitudinally using 7T MRI at predefined intervals (d7, d30, d90, and d180) post-SRS or earlier upon symptom onset. Histological analyses performed at each timepoint evaluated cell proliferation, apoptosis, vascular morphology, blood-brain/tumor-barrier integrity, hypoxia, TAM recruitment, and polarization. Immune cell populations within tumor microenvironment were characterized using flow cytometry. Statistical analyses included a T-test and one-way ANOVA with Bonferroni or Dunnett correction.</p><p><strong>Results: </strong>SRS efficacy was dose-dependent: 40-Gy suppressed tumor growth, while 20-Gy led to regrowth in 29% of cases between d30-51 post-SRS, necessitating stratification into responders and non-responders. Responders demonstrated reduced cell proliferation, sustained apoptosis, and vascular remodeling indicative of vessel normalization. Non-responders exhibited up to 94.5% increased hypoxia and up to 300-fold increased CXCR4 expression compared to responders. TAM recruitment inversely correlated with tumor volume (r=-0.8619, p=0.0056). The M1/M2 ratio in non-responders was similar to that of matched controls, but 3.8-fold and 4.8-fold lower than in responders at d30 and d90 post-SRS, respectively. FACS analysis confirmed an increased M1/M2 ratio by d30 in responders.</p><p><strong>Discussion: </strong>This study offers key insights into longitudinal SRS radiobiology, highlighting the dynamic role of TAMs in sustaining long-term tumor control. Our findings support an association between hypoxia, CXCL12/CXCR4 signaling, and treatment resistance, and suggest a potential SRS-induced vascular normalization that may support improved therapeutic outcomes. While not designed to establish causality, the data provide a spatially and temporally resolved framework to guide future mechanistic studies and inform more effective SRS-based combination strategies.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the FLASH Effect in a Rat Brain Organotypic Model with a Novel High Energy Electron Beam.","authors":"Tyler V Kay, Anna L Price, Markus Sprenger, Victoria J P Radosova, Andrew Thompson, Eric L Martin, Denise Dunn, Victor Popov, Stepan Mikhailov, Zachary J Reitman, Ying K Wu, Scott R Floyd, Mark Oldham","doi":"10.1016/j.ijrobp.2025.09.057","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2025.09.057","url":null,"abstract":"<p><strong>Purpose: </strong>Ultra-high dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control, however mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, HIGS (High Intensity Gamma Ray Source), paired with an organotypic ex vivo brain metastasis model.</p><p><strong>Methods: </strong>We varied inter-pulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma co-culture model of brain metastasis to assess effects on normal and neoplastic tissues. Live cell and bioluminescence imaging demonstrated cancer cell growth effects, while normal tissue responses and immune activation were assessed using live cell imaging, cytokine profiles, and confocal microscopy. We performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates.</p><p><strong>Results: </strong>The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in one pulse of 1 µs duration. Beam targeting was accurate to < 1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cell growth. HIGS-FLASH irradiation significantly increased TNFα and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation.</p><p><strong>Conclusions: </strong>Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}