International Journal of Radiation Oncology Biology Physics最新文献

EBRT-derived tolerance doses for long-term radiation toxicity (e.g., 23 Gy kidney limit) are routinely applied to radioligand therapy (RLT) for dosage selection in clinical trials. However, these thresholds are independent of the RLT molecule or patient populations, potentially leading to inaccurate toxicity assessments and suboptimal treatment.

Methods: The normal tissue complication probabilities (NTCP) curves are extrapolated from EBRT to RLT using the biologically effective dose (BED). Then the population level toxicity risk is calculated integrating the NTCP over the absorbed dose distribution in the organ at risk. The long-term risk observable in a population with a limited life expectancy can be further estimated as the cumulative incidence function. The method is applied to kidney absorbed dose data from the Erasmus MC clinical study of ¹⁷⁷Lu-DOTATATE. Simulations assessed the impact of absorbed dose variability and patients' life expectancy on toxicity risk and on the maximum cumulative activity, with sensitivity analysis on radiobiological and NTCP parameters.

Results: In 414 Erasmus MC patients, the mean kidney dose was 19 ± 5 Gy, with no treatment-related kidney failures during a median 78-month follow-up. The nephropathy risk estimated using BED was only 0.6%. Simulations showed toxicity risk depends on both mean dose and variability: a 5% 5-year nephropathy risk corresponded to at 22 Gy BED at a 50% coefficient of variation (CV), vs. 32 Gy at a 15% CV. A 20% higher administered activity with same risk could be administered in hypothetical patient population with 12-month survival compared to the Erasmus MC study population with 63 months survival. Radiobiological and NTCP parameter variations minimally affected maximum dose estimates.

Conclusion: The interindividual variability in kidney dosimetry and life expectancy in the treated population impact long-term toxicity risk at given cumulative activity. Accounting for these factors may enable more accurate estimation of toxicity risk and selection of administered activity, improving benefit-risk balance.

Background: Clinical trials suggest that adjuvant radiotherapy (RT) may be omitted in women aged 65 or older with early-stage, hormone-receptor (HR) positive breast cancer provided completion of 5 years of endocrine therapy (ET). However, at the time of RT consult, it is often unknown whether the patient will start ET or will start but not complete 5 years, either of which, if known in advance, would alter RT recommendations. We studied a cohort of patients who would have been eligible for RT omission to examine factors associated with declining or discontinuing ET.

Methods: Using a prospectively maintained institutional database, we identified patients age ≥65 who underwent surgery from 2010 to 2017 with stage I HR-positive breast cancer. Patients were classified as having osteopenia or osteoporosis based on the lowest T-score on DEXA. Missing data were replaced using multiple imputation. Recurrence and survival statistics were calculated using Kaplan-Meier analysis. Univariate and multivariate logistic regression was used to assess factors associated with not starting or discontinuing ET.

Results: We identified 590 eligible patients. Of these, 453 (76.8%) started ET. Patients who did not start ET were older (mean age 77.02 vs. 72.46, p < 0.001), had lower BMI (mean 25.36 vs. 26.78, p = 0.008), and lower DEXA scores (mean score -1.92 vs. -1.58, p = 0.056), and were less likely to undergo axillary surgery (64.2% vs. 86.8%, p < 0.001). Of the 453 patients who started ET, 315 (69.5%) completed at least 5 years. Discontinuation of ET was associated with older age (HR 1.082, 95% CI 1.033-1.133, p = 0.001), not undergoing axillary surgery (HR 0.365, 95% CI 0.146-0.915, p = 0.032) and smoking (HR 1.636, 95% CI 1.001-2.676, p = 0.05). Patients who were single or never married were less likely to discontinue ET (HR 0.281, 95% CI 0.096-0.821, p = 0.020). Patients who completed 5 years ET had significantly better local recurrence-free survival (96.8%) compared to those who stopped early (87.7%, p=0.01) or did not start ET (88.7%, p < 0.001).

Conclusions: Older age, osteopenia, and lower BMI were associated with not starting ET, while older age, marital status, axillary surgery, and smoking history predicted discontinuation of ET. These factors may guide discussions regarding the omission of adjuvant radiotherapy.

Purpose Stereotactic radiosurgery (SRS) is an effective treatment for brain arteriovenous malformations (AVMs), though radiation-induced adverse events (RAEs)-including peri-nidal T2 signal changes and late radiation-induced complications (LRICs)-remain concerns. We evaluated whether brain V12 (volume of surrounding brain receiving ≥12 Gy) predicts RAEs, including chronic encapsulated hematoma and cyst formation. Methods and Materials We retrospectively reviewed 317 patients who underwent SRS at a single institution between 1998 and 2020. Large AVMs with a nidus volume ≥10 mL were excluded. The primary outcome was the incidence of RAEs. Predictors of RAEs were identified using Cox proportional hazards models. Secondary outcomes included AVM obliteration and post-SRS hemorrhage. The optimal brain V12 cutoff for predicting symptomatic RAEs at 60 months post-SRS was identified using receiver operating characteristics analysis. Results The cohort included 176 males (56%), and 137 patients (43%) had prior hemorrhage. Median follow-up was 68 months (interquartile range [IQR]: 30-133). Peri-nidal T2 signal changes occurred in 149 patients (47%), including 129 (41%) transient and 20 (6%) permanent. Brain V12 was significantly associated with both transient (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.04-1.13, p < 0.01) and permanent (HR: 1.15, 95% CI: 1.07-1.24, p < 0.01) T2 changes. LRICs occurred in 15 patients (5%) at a median of 92 months (IQR: 59-140) and were more common in those with permanent T2 changes (40% vs. 5%, p < 0.01) and higher brain V12 (median 3.44 vs. 2.78 mL, p = 0.04). Brain V12 was an independent predictor of symptomatic RAEs (HR: 1.21, 95% CI: 1.14-1.28, p < 0.01), with an interpretable reference of 4.5 mL. Five-year cumulative AVM obliteration rate was 89%, and post-SRS hemorrhage rate was 4 per 1000 patient-years. Conclusions Brain V12 is a strong predictor of peri-nidal T2 signal changes, LRICs, and symptomatic RAEs. Limiting brain V12 may reduce complications while maintaining treatment efficacy.

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 non-invasively detect vascular injury METHODS AND MATERIALS: We utilized pseudo-continuous arterial spin labeling (pCASL) to evaluate the effects of single-dose total-body irradiation (TBI) or partial-body irradiation (PBI; 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 M, 8 F) and 93 received 1.14-8.5 Gy TBI or 9-10 Gy PBI (64 M, 29 F). Males ranged from 5-25 years old (median unirradiated = 10.1 y; median irradiated = 9.9 y); females ranged from 5-25 years old (median unirradiated = 18.7 y; median irradiated = 9.9 y). Radiation effects on CBF and CVR were also assessed in an age-matched subset of males aged 7-12 years old (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 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 Brachytherapy (HDR 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 XXX sites in the United States.

Methods: The primary objective was to analyze national brachytherapy (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 gynecological treatments involving more than three channels. Two-thirds of respondents were employed at non-academic institutions and 53% indicated that medical physics full-time equivalent was <1 at their clinic. The most frequently performed procedure was gynecological 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 (gyne) treatments, 38% reported the utilization of MRIs. Uptake of MRI-based planning appears to have only slightly increased over the past decade.

Conclusion: 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.

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

Methods: Adult patients with IDH-wild-type and IDH-mutant gliomas underwent NCF testing using the NIH Toolbox Cognition Battery and resting-state functional magnetic resonance imaging (rs-fMRI) before (baseline) and six months after RT. The battery assessed five cognitive domains and generated a fluid cognition composite score. NCF change (ΔNCF) 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 sub-cortical regions, defined by 300 rs-fMRI-derived regions of interests. Correlations between ΔNCF and dosimetric parameters were assessed using Spearman's rank correlation test (ρ). Linear regression models were compared using nested analysis of variance (ANOVA), Akaike Information Criterion (AIC), and adjusted R².

Results: Among 48 patients enrolled, 36 patients were evaluable with paired rs-fMRI and NCF data. Moderate negative correlations were observed between change in episodic memory (ΔNCF_EM) and mean dose to the medial temporal lobe network (MTL: ρ=-0.41, 95% CI=(-0.66, -0.08), P=0.01), visual network (VN: ρ=-0.42, 95% CI=(-0.67, -0.09), P=0.01), and parietal memory network (PMN: ρ=-0.40, 95% CI=(-0.65, -0.07), P=0.01). No significant correlations were found for other RSNs or NCF domains. A linear regression model incorporating MTL dose and its interaction with age outperformed the age-alone model in explaining variance in ΔNCF_EM (P=0.046; ΔAIC= -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 for identifying targets for cognitive preservation in patients undergoing RT.

The use of cardiac stereotactic body radiation therapy (SBRT) for the treatment of ventricular tachycardia (VT), also termed stereotactic ablative radiotherapy (SABR) or, increasingly, stereotactic arrhythmia radioablation (STAR), is increasingly utilized 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 CA. 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 radiotherapy.

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

Materials/methods: This prospective study included 23 patients with invasive breast cancer who underwent ALND/ILR followed by RNI. The anastomosis was indicated by a twirl clip allowing for ILR contouring. Median RNI dose was 4000cGy/16 fractions. Lymphedema was defined as an increase in arm volume (10% dominant, 7% non-dominant) in the affected extremity or 10-point increase in LDEX 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 (IQR, 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 (4135cGy vs. 1410cGy, p=0.006), V35 (89% vs. 20%, p=0.005), and V40 (84% vs. 17%, p=0.012) at the ILR + 2 cm volume compared to those that did not. These parameters remained significant after controlling for BMI and 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% vs 30%, p=0.006; V35, 56% (AUC 0.87), 92% vs 22%, p=0.001; and V40, 50% (AUC 0.83), 92% vs 30%, p=0.006.

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

Background: The association between late toxicity and biochemical recurrence (BCR) following prostate radiotherapy 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 radiotherapy.

Methods and materials: This was an individual patient data (IPD) meta-analysis that identified randomized phase III trials of CF or MHF prostate radiotherapy in the MARCAP 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 radiotherapy) 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. 6,761 patients were included (CF: n=4,333; MHF: n=2,428). Median follow-up was 72 months (interquartile range, 61-94 months). BCR occurred in 17.0% of patients (1,142/6,732). The rate of late grade ≥2 GI toxicity was 14.3% (965/6,761), while the rate of grade ≥2 GU toxicity was 15.5% (1,045/6,761). BCR was inversely associated with late grade ≥2 GI toxicity (sHR 0.64, 95% confidence interval [CI]: 0.43-0.96, p=0.03). BCR was not significantly associated with late grade ≥2 GU toxicity (sHR 1.06, 95% CI: 0.70-1.60, p=0.78).

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.