International Journal of Radiation Oncology Biology Physics最新文献

Purpose: Radiation-induced brain injury (RIBI) is partially defined by vascular injury, which contributes to long-term cognitive decline. RIBI is irreversible and progressive, highlighting the importance of early identification. Magnetic resonance imaging provides an opportunity to noninvasively detect vascular injury.

Methods and materials: We used pseudo-continuous arterial spin labeling to evaluate the effects of single dose total-body irradiation (TBI) or partial-body irradiation (5% lower limb sparing) on cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in 123 rhesus macaques (Macaca mulatta). Of these, 30 were unirradiated controls (22 male, 8 female) and 93 received 1.14-8.5 Gy TBI or 9-10 Gy partial-body irradiation (64 male, 29 female). The age of males ranged from 5-25 years (median unirradiated = 10.1 years; median irradiated = 9.9 years); the age of females ranged from 5-25 years (median unirradiated = 18.7 years; median irradiated = 9.9 years). Radiation effects on CBF and CVR were also assessed in an age-matched subset of males aged 7-12 years (14 controls, 46 TBI). To further characterize radiation-induced vascular change, GLUT-1-stained sections of frontal lobe and hippocampus from 21 (11 control, 10 irradiated) separate animals were evaluated for differences in microvessel density.

Results: In 7-12-year-old males, irradiation significantly affected CVR: mean CVR was 4.5% in controls versus 3.6% in irradiated animals. Among all controls, CVR declined significantly across age in both sexes (0.17% per year in males and 0.36% per year in females), whereas CVR did not change with age in irradiated animals. In females, both age and irradiation significantly influenced CVR, and a significant interaction was observed. Neither age nor irradiation significantly affected CBF in males or females. Furthermore, no radiation-induced differences in microvessel density were detected in the frontal lobe or hippocampus.

Conclusions: Our findings suggest that CVR decreases with age in macaques, supporting age-related neurodegeneration related to vascular change. Additionally, TBI at doses ≤8.5 Gy impaired CVR in male macaques, highlighting the utility of measuring CVR for detecting radiation-induced vascular injury and allowing for early intervention to mitigate RIBI.

Purpose: High-dose-rate (HDR) brachytherapy (BT) is an effective but resource-intensive treatment modality, demanding a highly skilled workforce, team coordination, and logistics. This study presents findings from a comprehensive national survey conducted in 2023, targeting all registered IROC-Houston (Imaging and Radiation Oncology Core) sites in the United States.

Methods and materials: The primary objective was to analyze national BT practice patterns and workload dynamics among medical physicists involved in HDR BT treatments. A secondary aim, explored in a companion publication (part 2), examines work effort, job satisfaction, and challenges faced by medical physicists in this field.

Results: The survey received 365 complete responses, revealing an experienced workforce, with 71% reporting over 10 years of BT service and 75% performing complex gynecologic treatments involving more than 3 channels. Two-thirds of respondents were employed at nonacademic institutions, and 53% indicated that the medical physics full-time equivalent was <1 at their clinic. The most frequently performed procedure was gynecologic BT (96%), followed by skin (34%), prostate (33%), and breast (23%). Adoption of advanced planning tools was variable, with 66% using inverse planning and 34% employing automatic catheter reconstruction. Additionally, 32% of all respondents performed magnetic resonance imaging (MRI) based planning, with 14% reporting frequent use. Of the subgroup performing complex gynecologic treatments, 38% reported the utilization of MRIs. Uptake of MRI-based planning appears to have increased only slightly over the past decade.

Conclusions: The survey demonstrated that medical physicists are involved in and responsible for nearly every technical aspect of the HDR BT process. This study presents one of the largest national surveys on medical physics practice patterns to date. The findings highlight ongoing challenges in allocating resources, varying procedure complexity, and logistical demands. Future initiatives should focus on developing improved resource allocation metrics to optimize staffing based on procedure complexity and caseload.

Purpose: To develop a competency-based simulation program to evaluate medical physics residents in radiation output measurements and clinical decision making.

Methods: A national working group developed methodology to assess competency of residents performing the measurement of radiation output for photon beams on a linear accelerator. The program included (i) pre- and post-task self-assessment, (ii) qualitative task evaluation, (iii) quantitative task evaluation, (iv) evaluator directed discussion and debrief, and (v) evaluator feedback. Eligible study participants were CAMPEP-accredited residents in medical physics. Evaluation was performed by a certified medical physicist directly observing the participant perform the simulation. Study outcomes included time-to-complete as well as qualitative scoring using a 30-point global rating scale (GRS) and quantitative measures including a procedural checklist for simulation accuracy and completeness. All statistical evaluations used an alpha of 0.05 to indicate significance.

Results: Over the study period, 39 residents participated from centers in Canada (n = 9) and the US (n = 2). The median (range) time-to-complete the simulation task for a single photon beam energy is 50 (24 to 139) minutes. In the self-assessment questionnaire with nine questions, the difference in pre- and post-task score was statistically significant (p < 0.001). On multivariable linear regression, residents earliest in their residency program (0 to 6 months) reported the largest improvement in preand post-assessment scores (p = 0.02). In the qualitative evaluation, the average (± standard deviation) global rating scores for the entire cohort were 26.1 (± 2.6). On multivariable linear regression, residents with prior hands-on experience in performing dosimetry measurements yielded a significantly improved GRS score (p < 0.01).

Conclusions: A competency-based simulation program was applied to medical physics residents in a structured, multi-institutional setting. These findings support the role of simulation-based environments in consolidating foundational dosimetry knowledge and clinical reasoning within medical physics residency training.

Purpose: In this prospective observational study, we evaluated dose-response relationships between radiation dose to the brain's resting-state networks (RSNs) and changes in neurocognitive function (NCF) following radiation therapy (RT) in adult patients with diffuse glioma.

Methods and materials: Adult patients with isocitrate dehydrogenase-wildtype and isocitrate dehydrogenase-mutant gliomas underwent NCF testing using the National Institutes of Health Toolbox Cognition Battery and resting-state functional magnetic resonance imaging (rs-fMRI) before (baseline) and 6 months after RT. The battery assessed 5 cognitive domains and generated a fluid cognition composite score. NCF change was defined as the percent change in age-adjusted scores from baseline to follow-up. Radiation dosimetric parameters were extracted for 13 RSNs and 3 subcortical regions, defined by 300 rs-fMRI-derived regions of interest. Correlations between NCF change and dosimetric parameters were assessed using Spearman's rank correlation test (ρ). Linear regression models were compared using a nested analysis of variance, the Akaike information criterion, and adjusted R².

Results: Of the 48 patients enrolled, 36 were evaluable with paired rs-fMRI and NCF data. Moderate negative correlations were observed between changes in episodic memory and the mean dose to the medial temporal lobe network (ρ = -0.41; 95% CI, -0.66, -0.08; P = .01), visual network (ρ = -0.42; 95% CI, -0.67, -0.09; P = .01), and parietal memory network (ρ = -0.40; 95% CI, -0.65, -0.07; P = .01). No significant correlations were found for other RSNs or NCF domains. A linear regression model incorporating medial temporal lobe dose and its interaction with age outperformed the age-only model in explaining variance in episodic memory change (P = .046; Akaike information criterion change = -2.95; adjusted R² = 0.313).

Conclusions: Focal dose-response relationships were observed between radiation dose to specific RSNs and episodic memory changes following RT, highlighting the prognostic and therapeutic potential of rs-fMRI in identifying targets for cognitive preservation in patients undergoing RT.

The use of cardiac stereotactic body radiation therapy for the treatment of ventricular tachycardia (VT), also termed stereotactic ablative radiation therapy or, increasingly, stereotactic arrhythmia radioablation (STAR), is increasingly used in select patients. STAR has emerged as a promising alternative to invasive catheter ablation (CA) for patients with high-risk refractory VT who have failed prior medical therapy or catheter ablation. Since the publication of the first case series using STAR, our understanding of the mechanisms of STAR, longer-term clinical outcomes, potential side effects, and barriers to widespread adoption of cardiac radioablation has become increasingly clear. In this review, we discuss these topics, the increased adoption of STAR, as well as the challenges that lie ahead for this therapy. In addition, as data strongly suggest that fibrosis alone cannot account for the early decreases in VT events observed post-STAR, we propose adopting the STAR acronym to instead stand for stereotactic arrhythmia radiation therapy.

Purpose: Regional nodal irradiation (RNI) increases breast cancer-related lymphedema (BCRL) following axillary lymph node dissection despite immediate lymphatic reconstruction (ILR). This study examines the relationship between radiation (RT) dose to the ILR anastomosis and BCRL.

Methods and materials: This prospective study included 23 patients with invasive breast cancer who underwent axillary lymph node dissection/ILR followed by RNI. The anastomosis was indicated by a twirl clip, allowing for ILR contouring. The median RNI dose was 4000 cGy in 16 fractions. Lymphedema was defined as an increase in arm volume (10% dominant, 7% nondominant) in the affected extremity or a 10-point increase in Lymphedema Index plus patient-reported symptoms >6 months after RT completion. Dosimetric parameters included mean and maximum doses, V35, V40, Dmin<36.8Gy at the ILR site, ILR + 5 mm, and ILR + 2 cm expansion volumes.

Results: Median follow-up was 25.9 months (interquartile range, 22.8-33.9). Fourteen patients met criteria for lymphedema at >1 time point, but only 4 (17.4%) met criteria for BCRL at their last follow-up. Patients who developed lymphedema had higher mean dose (4135 cGy vs 1410 cGy; P = .006), V35 (89% vs 20%; P = .005), and V40 (84% vs 17%; P = .012) at the ILR + 2 cm volume compared with those who did not. These parameters remained significant after controlling for BMI and the number of nodes removed. Threshold doses for lymphedema risk were found for the ILR + 2 cm volume: mean dose, 3074 cGy (AUC = 0.86), with rates of lymphedema above and below the threshold at 92% versus 30%, P = .006; V35, 56% (AUC = 0.87), 92% versus 22%, P = .001; and V40, 50% (AUC = 0.83), 92% versus 30%, P = .006.

Conclusions: Increasing RT doses to the ILR anastomosis site and the surrounding area increased lymphedema risk. Future studies will assess whether limiting the dose below these thresholds can lower BCRL rates while maintaining disease control.

Purpose: The association between late toxicity and biochemical recurrence (BCR) after prostate radiation therapy is unclear. We set out to characterize the relationship between late gastrointestinal (GI) and genitourinary (GU) toxicity and BCR among patients receiving conventionally fractionated (CF) or moderately hypofractionated (MHF) prostate radiation therapy.

Methods and materials: This was an individual patient data meta-analysis that identified randomized phase 3 trials of CF or MHF prostate radiation therapy in the MARCAP (Meta-Analysis of Randomized trials in Cancer of the Prostate) Consortium that had individual-level late toxicity and BCR data available. Data were provided to MARCAP by study investigators. The associations between BCR and late (>3 months after radiation therapy) grade ≥2 GI and GU toxicities were assessed using Fine-Gray subdistribution hazard models with an 18-month landmark to address immortal time bias.

Results: Seven of 26 available trials met all eligibility criteria. A total of 6761 patients were included (CF: n = 4333; MHF: n = 2428). Median follow-up was 72 months (IQR, 61-94 months). BCR occurred in 17.0% of patients (1142/6732). The rate of late grade ≥2 GI toxicity was 14.3% (965/6761), although the rate of grade ≥2 GU toxicity was 15.5% (1045/6761). BCR was inversely associated with late grade ≥2 GI toxicity (subdistribution hazard ratio, 0.64; 95% CI, 0.43-0.96; P = .03). BCR was not significantly associated with late grade ≥2 GU toxicity (subdistribution hazard ratio, 1.06; 95% CI, 0.70-1.60; P = .78).

Conclusions: Late grade ≥2 GI toxicity was significantly associated with lower rates of BCR. We hypothesize that this may be related to the impact of prostatic motion during treatment, specifically anterosuperior motion of the prostate that would increase the dose to the rectum and to posterior dominant intraprostatic lesions. Late grade ≥2 GU toxicity did not appear to be associated with BCR.

Purpose: Recurrent WHO grade 4 gliomas have poor outcomes and limited salvage options. Reirradiation (re-RT) can provide local control in selected patients but is constrained by cumulative dose and toxicity. Personalized ultrafractionated stereotactic adaptive radiation therapy (PULSAR) delivers re-RT as high-dose "pulses" spaced weeks apart, creating opportunities for interim magnetic resonance imaging (MRI) assessment and adaptive replanning on an MRI-linear accelerator METHODS AND MATERIALS: We retrospectively analyzed 45 patients with recurrent WHO grade 4 gliomas treated with MRI-guided PULSAR re-RT on a 1.5-T MRI-linear accelerator (5 planned pulses; typical prescription 25-35 Gy in 5 fractions with dose painting). A 0-5-mm expansion from either or both GTVs was used to generate the treated CTV without an additional PTV margin. On-treatment MRI (T1 postcontrast ± T2-FLAIR) was used for volumetric assessment and adaptive replanning when indicated. Endpoints included overall survival (OS), progression-free survival (PFS), local failure (LF), and grade ≥3 toxicity (cerebral edema or hematologic events). Univariable regression explored associations between clinical factors and outcomes.

Results: Median age was 54.2 years; 78% of tumors were IDH wild type, with frequent corpus callosum involvement (68.9%) and multifocal/multicentric disease (40.0%). Thirty-six patients (80%) underwent ≥1 adaptive replan, and 30 (66.7%) completed the planned course. Median follow-up was 16.7 months. Median OS and PFS from re-RT start were 6.9 and 5.1 months, respectively. The 12-month cumulative incidence of LF was 56.0% (68.0% in a sensitivity analysis accounting for cause-specific mortality). The 12-month cumulative incidence of grade ≥3 cerebral edema was 40.0%, and grade ≥3 hematologic toxicity was 38.0%. Concurrent bevacizumab was associated with a lower incidence of grade ≥3 cerebral edema (20% vs 60%; HR = 0.32; P = .04). ECOG performance status ≥2 and IDH wild type status were associated with worse OS and PFS. Volumetric response on T1 postcontrast or T2-FLAIR imaging was not significantly associated with OS or PFS.

Conclusions: MRI-guided PULSAR re-RT with adaptive replanning was feasible in a high-risk recurrent WHO grade 4 glioma cohort. Interim MRI assessment supported real-time treatment decision-making, but the clinical benefit of this adaptive strategy relative to conventional re-RT remains unclear without a control arm. Prospective studies are needed to standardize imaging/adaptation workflows, optimize pulse spacing, refine margin strategies, and determine whether MRI-guided adaptive PULSAR improves clinically meaningful outcomes.

Purpose: In reirradiation, tumor control must be balanced against a high-risk of adverse effects. We evaluated the feasibility of a time-dependent recovery model to improve toxicity prediction.

Methods and materials: Sixty-five high-risk thoracic reirradiation patients, identified by BID treatment, were included for modeling grade ≥2 acute esophagitis. The median (range) re-RT dose was 45 Gy (30-60) in 30 (20-40) fractions. Doses from each course were deformably registered to the most recent CT and converted to voxel-wise equivalent dose in 2-Gy fractions. We compared the discrimination of the last course dose, conventional direct accumulation without time consideration, and 3 time-dependent recovery models-mono-exponential, bi-exponential, and reciprocal time-each optimized via grid search with nested 5-fold cross-validation. Logistic regression with bootstrapping was used to assess the predictive value of mean and maximum dose. AUCs were compared using a bootstrap test. Covariates (age, chemotherapy, smoking status, and history of esophagitis from a previous course of thoracic radiation therapy) were also evaluated.

Results: After BID re-RT, 26.2% (17/65) of patients experienced grade ≥2 esophagitis. Incorporating time-dependent repair algorithms achieved a higher AUC than the last course dose and direct accumulation. The bi-exponential model incorporating history of prior esophagitis achieved the highest performance (mean dose AUC: 0.83 [95% CI, 0.70-0.94] vs direct accumulation: 0.74 [0.61-0.87], P = .040; maximum dose AUC: 0.78 [0.65-0.89] vs 0.67 [0.54-0.80], P = .015).

Conclusions: Incorporating time-dependent recovery into dose accumulation is feasible, and our findings support its potential use over direct accumulation for more accurate toxicity prediction. These findings will pave the way for developing advanced outcome models for evidence-based reirradiation, ultimately reducing toxicity and optimizing doses for personalized and effective reirradiation.

Purpose: The reported incidence of subsequent malignant neoplasms (SMNs) in long-term survivors of pediatric classic Hodgkin lymphoma (cHL) is based on patients treated with outdated radiation therapy (RT) doses and techniques. The risk associated with modern mediastinal RT in pediatric cHL is unknown.

Methods and materials: We modeled the risk of SMN in children with cHL who enrolled in the multi-institutional Children's Oncology Group AHOD1331 trial (2015-2019) and received mediastinal RT.

Results: Among 587 trial patients, 296 (50%) received mediastinal RT and were eligible for this analysis. Proton therapy was used for 25%, photon intensity modulated RT (IMRT) for 46%, and photon 3-dimensional conformal RT (3D-CRT) for 28%. The RT prescription dose was 21 Gy in 83% and 30 Gy in 16%. The estimated mean lifetime attributable risk at 70 years of age of breast carcinoma (females) was 2.92% (1.45% proton; 4.36% IMRT; 1.82% 3D-CRT; P < .0001), lung carcinoma was 5.37% (4.15% proton; 6.24% IMRT; 5.07% 3D-CRT; P < .0001), and thyroid carcinoma was 0.17% (0.25% proton; 0.17% IMRT; 0.12% 3D-CRT; P = .271). The predicted risk of breast carcinoma was higher among female patients treated with their arms raised versus arms down (P < .0001).

Conclusions: Normal tissue doses associated with contemporary mediastinal RT produce lower predicted SMN risks than were observed in cohorts treated with historical RT approaches, with substantial variation among individuals. On average, proton therapy is associated with a lower predicted risk. These findings have implications for the selection of therapies, counseling of patients, planning of RT, and recommendations for SMN screening.