International Journal of Radiation Oncology Biology Physics最新文献

Purpose: Curative-intent pelvic radiation for cervical cancer causes premature ovarian insufficiency (POI) in premenopausal patients. Despite evidence-based recommendations for hormone replacement therapy (HRT) to treat POI, prior studies have shown low HRT use among cervical cancer survivors, particularly those treated with radiation. This study evaluates the impact of practice quality improvement (PQI) initiative within a radiation oncology department on the rates of HRT prescriptions, POI documentation, and counseling.

Patients and methods: A retrospective chart review was conducted on premenopausal patients aged ≤50 years who received curative-intent radiation for cervical cancer at a single institution from 2018 - 2024. Rates of POI-related counseling and HRT prescriptions were evaluated before and after a PQI intervention targeting POI treatment. HRT prescriptions were stratified by physiologic sex steroid replacement regimens (PSSRR), defined as ≥0.1 mg/day transdermal or ≥2 mg oral 17β-estradiol, vs. other regimens, including oral contraceptives and non-replacement doses of physiologic sex steroid regimens. Binary outcomes were analyzed using generalized estimating equations.

Results: Sixty patients met inclusion criteria. Patients seen after PQI intervention implementation had 2.1 times higher odds of receiving any HRT prescription, PSSRR or non-PSSRR, than patient seen before PQI intervention implementation (OR = 2.09, p = 0.015). PSSRR prescriptions increased from 3.4% pre-intervention to 57.7% post-intervention, with 80.7% of patients seen by an advanced practice provider (APP) receiving PSSRR. POI documentation increased from 48.3% to 80.8%, and inclusion on the problem list increased from 6.9% to 34.6%. High-quality POI counseling improved from 6.9% to 44.2%, and high-quality HRT counseling improved from 0.0% to 46.2%.

Conclusion: The radiation oncology department-based PQI initiative significantly improved documentation, counseling, and PSSRR prescriptions for cervical cancer survivors.

Purpose: Stereotactic ablative radiotherapy (SAbR) is increasingly employed to treat limited sites of oligoprogression in metastatic renal cell carcinoma (OP-mRCC) during systemic therapy (ST). The patient subgroups most likely to benefit remain undefined.

Methods: We retrospectively analyzed 96 patients with OP-mRCC who received SAbR to 153 lesions between 2010 and 2023, representing one of the largest and longest-followed cohorts reported to date. We applied the novel endpoint of modified progression-free survival (mPFS), defined as time from SAbR to ST switch or death, and evaluated systemic therapy escalation (E-ST) as a competing-risk event. Secondary endpoints included overall survival (OS), local control, and toxicity.

Results: At a median follow-up of 59 months (IQR 44-70), median mPFS was 9.2 months, with a 1-year estimate of 38% (95% CI 29-49). Compared with patients with one lesion, those with 2-3 (HR 2.10, 95% CI 1.29-3.43, p=0.003) and 4-5 lesions (HR 2.84, 95% CI 1.00-8.13, p=0.05) had significantly higher hazard of ST switch or death. Patients receiving immunotherapy showed a non-significant evidence towards improved mPFS (HR 0.66, 95% CI 0.41-1.05, p=0.08). More than one prior line of ST before SAbR was associated with worse OS (HR 1.29, 95% CI 1.02-1.65, p=0.04). Local control was 93%, with only one grade 3 toxicity.

Conclusion: In OP-RCC treated with SAbR, patients with a single progressing lesion had the best outcomes. This approach provided high local control with minimal toxicity while deferring systemic therapy escalation, supporting its role as a resource-sparing, patient-centered strategy. Patients treated concurrently with immunotherapy demonstrated a non-significant evidence toward improved outcome, highlighting the need for prospective studies to determine whether SAbR affects benefit from immunotherapy in selective patients.

Background: The majority of Head and Neck Squamous Cell Carcinoma (HNSCC) patients receives radiotherapy (RT) as part of their treatment plan. Even though RT is highly effective in HNSCC, therapeutic efficacy for advanced HNSCC is relatively low; a third of radiotherapy-treated HNSCC patients experiences locoregional relapse within 5 years after treatment. Cancer-associated fibroblasts (CAFs) are one of the most prominent cell types in the tumor micro-environment (TME) in advanced HNSCC and play a key role in therapy resistance.

Methods and materials: Here, we characterize the response of primary human HNSCC-derived CAFs to radiation and its consequences for CAF function and explore the targetability of radiation-induced senescent CAFs.

Results: Using primary human HNSCC-derived CAFs, we show that CAFs survive single-dose RT up to 68 Gy, and fractionated doses of 3×8 Gy; CAFs do not die but go into senescence after radiation. Importantly, we show that the CAF secretome is capable of enhancing both HNSCC cell proliferation and migration, and that CAFs retain these capabilities after radiation. Lastly, we demonstrate that irradiated CAFs display increased sensitivity to Navitoclax (ABT-263), a senolytic drug that selectively induces cell death in senescent cells.

Conclusions: This work highlights the importance of CAFs in radiotherapy and offers rationale for exploring combinations of radiotherapy and CAF-targeting approaches in HNSCC.

Purpose: This study evaluated whether the difference in total Medicare costs between active surveillance (AS) vs. radiotherapy (RT) changed over time for men with low- or favorable-intermediate risk prostate cancer.

Methods and materials: Using SEER-Medicare data, we calculated the costs associated with AS vs. four RT modalities: brachytherapy, stereotactic body radiation therapy (SBRT), intensity-modulated radiation therapy (IMRT), and proton beam therapy. We included costs which pertained to treatment, surveillance, and morbidity management for each patient, for three years after diagnosis. Costs were adjusted to 2017 dollars. Multivariable models assessed whether the cost gap between AS and RT changed between patient diagnosed in two time periods (2010-2014 vs. 2015-2019).

Results: AS costs increased over time, driven by surveillance and morbidity expenses, while RT costs decreased across treatment, surveillance, and morbidity. After adjusting for patient and clinical factors, the cost gap between AS and RT (all modalities combined) decreased by a mean of $3,777 from the earlier to later period. A decrease in the cost gap over time between AS vs. radiotherapy was observed for all radiotherapy modalities ($607 for brachytherapy, $4,408 for SBRT, $5,385 for IMRT, and $3,663 for proton therapy), although it was not statistically significant for brachytherapy.

Conclusions: While AS remains the least costly approach, the cost gap between AS and RT has decreased over time, which may be related to intensification of AS and de-intensification of RT.

Purpose: This cross-sectional study examines disparities in access to radiotherapy (RT) across Brazil, a country with a population exceeding 210 million, focusing on the distances traveled by cancer patients to receive RT. Using data from 2017 to 2022, the study aimed to assess geographical barriers to radiation therapy access and regional inequities.

Methods and materials: Data from the Brazilian National Outpatient Procedure Authorization (APAC) system were collected as .dbc files and processed using Python. Variables included procedure type, procedure year, patient demographics (sex and race), patient's city of residence, and treatment location (state and region). Additionally, the data captured whether the treatment necessitated travel to another city. Distances between patients' residences and treatment facilities were calculated using the Haversine formula and analyzed in kilometers (km). This data was incorporated into a Power BI database for analysis. Statistical significance was assessed using T-tests ANOVA, ANOVA weighted, ANCOVA, and to account for both location and demographic factors to account for both location and demographic factors, such as race and sex with a threshold of p < 0.05.

Results: The study analyzed 840,779 RT procedures, of which 514,237 required intercity travel, while 326,542 were performed locally. The national average distance to access RT in Brazil was 120.1 km, with significant changes in nationwide distances from 2017 to 2022 (p<0.001). Regional disparities were pronounced, with mean distances of 442.2, 238.9, 161.8, 73.8, and 71.3 km in the North, Midwest, Northeast, Southeast, and South regions, respectively (p<0.001). The North region demonstrated the most significant improvement in the average distance to radiation from 2017 to 2022, with an 81.8 km reduction in distance (p=0.009). The Southeast and South regions also experienced modest but statistically significant changes overtime (p<0.05). Sex also influenced travel distances; females traveled an average of 122.3 km and males 117.3 km (p = 0.041). The distance also varied by procedure type and RT anatomical site indication (p<0.001).

Conclusions: This study reveals considerable geographic disparities in RT access in Brazil, with marked differences observed among residents in less developed regions, and females. These findings point to potential and persistent inequities that may help to guide the strengthening of the healthcare infrastructure and developing targeted strategies to promote more equitable access to cancer treatment nationwide.

Background: Although MRI is the gold standard for image guided brachytherapy (IGBT) for cervix cancer, CT scan is widely used. However, there is dearth of comparative evidence.

Methods: Patients with FIGO (2018) stage IB3 - IVA treated with (chemo)radiation and CT-Ultrasound or MRI-based IGBT from 2016 to 2023 were included. The planning aim was to achieve D90 of ≥ 85 Gy₁₀ to high-risk clinical target volume (HRCTV) and ≤ 90 Gy₃, ≤ 75 Gy₃ and ≤ 75 Gy equivalent dose in 2 Gy (EQD2) to 2cc bladder, rectum and sigmoid, respectively. Propensity score matching (PSM) was performed to compare local control, disease-free survival and adverse events. Univariate and multivariable analyses were performed using log-rank test and Cox Regression model. Post hoc power analysis was performed for non-inferiority margin of 5%, assuming α = 0.15.

Results: Out of the 689 patients, 240 were eligible for PSM (120 each in CT and MRI cohort). Median HRCTV was 34 cc (IQR: 26 - 42). Forty-three percent (n = 104) of patients underwent intracavitary-interstitial brachytherapy (IC-ISBT), whereas others received ICBT. At a median follow up of 35.3 months, there was no difference in 3-year local control (LC) and disease-free survival (DFS) between CT and MRI cohorts [LC: 89% (95% CI: 82-97%) vs. 92% (95% CI: 87-97%) p = 0.71; DFS: 71% (95% CI: 62 - 82%) vs. 73% (95% CI: 65 - 81%), p = 0.86; respectively]. Late grade ≥ 3 gastro-intestinal and genitourinary toxicities were comparable [(8.2 vs. 11%, p = 0.51) and (2.5 vs. 4.2%, p = 0.49)]. The hazard ratio for non-inferiority of CT was 0.84 (95% CI, 0.34-2.07) with power of 0.69.

Conclusions: CT- based brachytherapy may provide comparable outcomes to MRI-based BT. The results of the study should be considered hypothesis-generating needing validation in prospective studies.

Purpose: Thyroid dysfunction is a common complication of breast regional nodal irradiation (RNI). Proton therapy has been posed as a means to spare normal tissue. We prospectively evaluated the incidence of hypothyroidism in a cohort of patients receiving RNI on a randomized trial comparing proton to photon modalities. A secondary objective was to evaluate the associations between thyroid dose-volume metrics and the risk of subsequent hypothyroidism.

Methods: We conducted a single-institution prospective correlative study within the randomized phase III Radiotherapy Comparative Effectiveness (RadComp) trial. Thyroid function testing was obtained at baseline, annually to 3 years, and at 5 years. Clinical hypothyroidism was defined as elevated thyroid stimulating hormone above institutional range with recommendation for or initiation of thyroid replacement therapy. Cumulative incidence of hypothyroidism after proton and photon RNI were compared using fine-gray regression. Thyroid dose-volume metrics were also explored as potential predictors of hypothyroidism, including previously validated metrics, thyroid Dmean>21 Gy(RBE) and thyroid volume spared from 20 Gy(RBE) (VS20Gy(RBE)).

Results: Ninety-two patients enrolled; seventy-one patients met criteria for analysis (proton 38, photon 33). Median follow-up was 66 months. The 3-year cumulative incidence of clinical hypothyroidism was 13%. By modality, incidence was 16% (proton) versus 9% (photon) (p=0.14). Stratifying by technique, the incidence of hypothyroidism was 0% for 3-dimensional conformal radiation therapy (3DCRT) and 16% for both intensity modulated radiation therapy (IMRT) and pencil beam scanning (p=0.26). Dmean>21 Gy(RBE) (HR=3.02, 95% CI 1.02-8.98) and VS20Gy(RBE)<2.2 cc (HR=8.80, 95% CI 1.54-50.30) were associated with hypothyroidism.

Conclusion: After RNI, the 3-year incidence of clinical hypothyroidism was 13%, with no statistically significant difference between proton and photon modalities. Thyroid Dmean>21 Gy(RBE) and VS20Gy(RBE)< 2.2 cc were associated with higher risk of hypothyroidism. Inverse planned RNI with superior coverage of the supraclavicular fossa, may come at the expense of increased thyroid dose.

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.