International Journal of Radiation Oncology Biology Physics最新文献

Purpose: The value of integrating clinical variables, radiomics, and tumor-derived cell-free DNA (cfDNA) for the prediction of survival and response to chemoradiation of patients with resectable esophageal adenocarcinoma is not yet known. Our aim was to investigate if radiomics and cfDNA metrics combined with clinical variables can improve personalized predictions.

Methods and materials: A cohort of 111 patients with resectable esophageal adenocarcinoma from 2 centers treated with neoadjuvant chemoradiation therapy was used for exploratory retrospective analyses. Models combining the clinical variables of the SOURCE survival model with radiomic features and cfDNA were built using elastic net regression and internally validated using 5-fold cross-validation. Model performance for overall survival (OS) and time to progression (TTP) were evaluated with the C-index and the area under the curve for pathologic complete response.

Results: The best-performing baseline models for OS and TTP were based on the combination of SOURCE-cfDNA that reached a C-index of 0.55 and 0.59 compared with 0.44 to 0.45 with SOURCE alone. The addition of restaging positron emission tomography radiomics to SOURCE was the most promising addition for predicting OS (C-index: 0.65) and TTP (C-index: 0.60). Baseline risk stratification was achieved for OS and TTP by combining SOURCE with radiomics or cfDNA, log-rank P < .01. The best-performing combination model for the prediction of pathologic complete response reached an area under the curve of 0.61 compared with 0.47 with SOURCE variables alone.

Conclusions: The addition of radiomics and cfDNA can improve the performance of an established survival model. External validity needs to be further assessed in future studies together with the optimization of radiomic pipelines.

Purpose: This was a phase 1 trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk volume-adapted, hypofractionated, postoperative radiation therapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression-free survival and quality of life (QOL).

Methods and materials: Patients were treated with 1 of 3 isoeffective DSs (DS1: 20 fractions, DS2: 15 fractions, and DS3: 10 fractions) that escalated the dose to the imaging-defined local recurrence (73 Gy₃ equivalent dose in 2Gy fractions) and de-escalated the dose to the remainder of the prostate bed (48 Gy₃ equivalent dose in 2Gy fractions). Escalation followed a standard 3 + 3 design with a 6-patient expansion at the maximally tolerated hypofractionated DS. Dose-limiting toxicity was defined as Common Terminology Criteria for Adverse Events v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or G4 gastrointestinal (GI) or genitourinary toxicities thereafter. QOL was assessed longitudinally through 24 months with the Expanded Prostate Cancer Index Composite short form.

Results: Between January 2018 and December 2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No dose-limiting toxicities were observed on any DS, and thus, expansion occurred at DS3. The cumulative incidence of G3 GI and genitourinary toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was the most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The biochemical progression-free survival was 91% at both 24 and 60 months.

Conclusions: The maximally tolerated hypofractionated DS for hypofractionated, risk volume-adapted PORT was determined to be DS3 (36.4 Gy to the prostate bed and 47.1 Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.

Purpose: Although postirradiation hyposalivation significantly impairs patient quality of life, the underlying mechanisms driving radiation-induced salivary gland fibrosis and hyposalivation remain poorly understood. This study aims to explore the role of calcium-mediated signaling pathways in radiation-induced salivary gland fibrosis.

Methods and materials: Primary human submandibular gland (SG) cells and C57BL/6J female mouse SGs were exposed to irradiation to model fibrosis development. Following 15 Gy irradiation exposure, RNA sequencing and bioinformatic analysis were conducted on mouse SGs. The effects of store-operated calcium entry (SOCE) inhibition using SKF96365 and YM58483 on fibrosis markers were assessed in vitro and in vivo. Additionally, the involvement of ORAI2 protein and the newly identified JNK/NFAT1/transforming growth factor β1 (TGF-β1) signaling axis in SG fibrosis was explored.

Results: We identified that the calcium release-activated calcium modulator ORAI2 was important in promoting early-stage postirradiation fibrosis in SGs. Calcium channel signaling was activated in both human patients and irradiated C57BL/6J female mice SGs. Inhibition of SOCE signaling effectively blocked fibrosis in an ORAI2-dependent manner 30 days after irradiation. Our mechanistic studies revealed a novel ORAI2/JNK/NFAT1 axis within the SOCE pathway critical in driving TGF-β1-mediated fibrogenesis. Encouragingly, pharmacologic inhibition of NFAT1 significantly mitigated radiation-induced SG fibrosis and restored saliva flow to 84.61% of normal levels in treated mice 30 days after irradiation, without detectable side effects.

Conclusions: Our findings highlight the significance of the ORAI2-mediated calcium signaling pathway, specifically via the ORAI2/JNK/NFAT1 axis, in promoting TGF-β1 expression and contributing to the development of early-stage salivary gland fibrosis following irradiation exposure. Targeting the ORAI2/JNK/NFAT1 axis emerges as a promising therapeutic strategy to alleviate radiation-induced hyposalivation and fibrosis, potentially improving the quality of life for patients undergoing radiation therapy.

Purpose: The Imaging Radiation Oncology Core (IROC) head and neck (H&N) phantom is used to credential institutions for intensity modulated radiation therapy delivery for all anatomic sites where delivery of modulated therapy is a primary challenge. This study evaluated how appropriate the use of this phantom is for varied clinical anatomy by evaluating how closely the IROC H&N phantom described clinical dose errors from beam modeling compared with various anatomic sites.

Methods and materials: The multileaf collimator (MLC) offset, transmission, percent depth dose, and 7 additional beam modeling parameters for a Varian accelerator were modified in RayStation to match community data at the 2.5th, 25th, 50th, 75th, and 97.5th percentile levels. Modifications were evaluated on 25 H&N phantom cases and 25 clinical cases (H&N, prostate, lung, mesothelioma, and brain), generating 2000 plan perturbations. Differences in mean dose delivered to clinical target volumes and maximum dose to organs at risk were compared between phantom and clinical plans to assess the relationship between dose deviations in phantom versus clinical target volumes and as a function of 18 different complexity metrics.

Results: Perturbations to MLC offset and transmission parameters demonstrated the greatest impact on dose accuracy for phantom and clinical plans (for all anatomic sites). The phantom demonstrated equivalent or greater sensitivity to these parameter perturbations compared with clinical sites, largely aligning with treatment complexity. The mean MLC gap best described the impact of errors in treatment planning system beam modeling parameters in phantom plans and clinical plans from various anatomic sites.

Conclusions: When compared across various anatomic sites, the IROC H&N credentialing phantom exhibited similar or greater sensitivity to errors in the treatment planning system. As such, it is a suitable surrogate device for assessing institutional performance across various anatomic sites. If an institution successfully irradiates the phantom, that result confers confidence that intensity modulated radiation therapy to a wide range of anatomic sites can be successfully delivered by the institution.