International Journal of Radiation Oncology Biology Physics最新文献

Background: Functional magnetic resonance imaging (fMRI) localizes eloquent areas of the brain more accurately than structural imaging alone and minimizes the risk of neurosurgical injury. However, fMRI remains underutilized in stereotactic radiosurgery (SRS). We assessed the neuroanatomic relationship between SRS to brain metastases (BM), nearby eloquent areas, identified using fMRI, and attributable symptoms of radionecrosis (RN). We then evaluated the advantage of a novel fMRI-guided SRS (fMRI-SRS) planning approach.

Methods: Patients with an fMRI study within three months of SRS for BM were included. The nearest eloquent area (NEA) was defined as the motor, language, or visual eloquent area on fMRI nearest to an irradiated BM. The primary outcome was focal symptomatic RN (FSRN), defined as radiographic RN with progressive neurologic symptoms localizable to the NEA. The relationship between dose to the NEA and risk of FSRN was assessed with logistic regression. Cases were replanned using fMRI-SRS, maximizing NEA avoidance while maintaining target coverage.

Results: Among 93 patients, 76 (82%) had resection prior to SRS. The most common SRS prescription was 30 Gy in 5 fractions. The NEA was a motor eloquent area in 71 cases (76%) and a language area in 18 cases (19%). Of 20 patients who developed radiographic RN, 4 (20%) were asymptomatic, 4 (20%) had nonlocalizable neurologic symptoms, and 12 had focal neurologic symptoms directly attributable to the NEA, consistent with FSRN. Among patients who received 5-fraction SRS with modern planning techniques, greater V14Gy (single-fraction equivalent) to the NEA predicted increased risk of FSRN at 18 months (OR 6.8/mL, p=0.05). fMRI-SRS reduced NEA V14Gy in all cases replanned, with a mean reduction of 22.5%.

Conclusions: Focal neurologic symptoms of RN reflect SRS dose to nearby eloquent areas on fMRI. fMRI-SRS planning minimizes dose to eloquent areas without sacrificing target coverage and may mitigate neurologic toxicity.

Rationale: Several individuals with Prostate Cancer (PCa) develop metastatic castration-resistant prostate cancer (mCRPC) after current treatment, that has a death rate of more than 50%. Although many approaches target mCRPC and show promising results, mCRPC is still incurable. Therefore, we aimed to investigate the efficacy and dosimetry of alpha (²²⁵Ac) versus beta (¹⁷⁷Lu) radiopharmaceutical therapy (RPT) using NM600 in murine prostate cancer models.

Methods: NM600 was radiolabeled with ¹⁷⁷Lu and ²²⁵Ac for targeted radionuclide therapy, and therapeutic efficacy. ¹⁷⁷Lu-NM600 SPECT/CT imaging was conducted on syngeneic Myc-CaP and TRAMP-C1 prostate cancer mouse models, and they were administered 7.4 MBq of ¹⁷⁷Lu-NM600 in the tail vein. We calculated the dosimetry of ¹⁷⁷Lu-NM600 therapy using the SPECT/CT imaging data and the biodistribution study. The complete blood count (CBC), comprehensive metabolic panel (CMP), and histology analysis were carried out to assess toxicity in Myc-CaP and TRAMP-C1-beering mice (n = 9), that were given 5.55 (low IA) or 18.5 MBq (high IA) of 177Lu-NM600, and 7.4 (low IA) or 18.5 KBq (high IA) of ²²⁵Ac-NM600. Finally, the overall survival and tumor growth rate were monitored for all groups.

Results: Both ²²⁵Ac/¹⁷⁷Lu-NM600 demonstrated tumor-specific uptake and retention. ²²⁵Ac-NM600 exhibited superior antitumor effects and significantly improved overall survival compared to ¹⁷⁷Lu-NM600 at similar doses. The enhanced efficacy of ²²⁵Ac-NM600 was attributed to its higher relative biological effectiveness. Toxicity studies revealed transient, dose-dependent hematological changes for both agents, with no significant long-term adverse effects.

Conclusion: ²²⁵Ac-NM600 demonstrated enhanced antitumor efficacy compared to ¹⁷⁷Lu-NM600 in murine prostate cancer models, with a favorable toxicity profile. These outcomes reveal a strong rationale for further developing alpha-emitting RPT agents for prostate cancer treatment.

Purpose/objectives: As survival improves for patients with brain metastases, distinguishing local recurrence(LR) from radionecrosis(RN) is a growing neuro-oncologic challenge. We aimed to develop an explainable deep learning(DL) model to non-invasively distinguish RN from LR in patients with non-small cell lung cancer(NSCLC) following stereotactic radiosurgery(SRS).

Materials/methods: A 2^nd order Heavy-Ball Neural Ordinary Differential Equation(HBNODE) DL framework was designed. It enabled dynamic tracking of input evolution within DNN, integrating MR, clinical, and genomic features into a unified Image-Genomic-Clinical(I-G-C) space. This allowed visualization of sample trajectories during model execution. Layer-Wise Relevance Propagation(LRP) was applied to quantify individual non-imaging feature contributions and their influence on diagnosis. Within the I-G-C space, a decision-making field(F) was reconstructed. The temporal evolution of F enabled quantitative comparison of cumulative contributions from each feature. Key intermediate states, defined as locoregional equilibrium points(∇F=0), were identified and aggregated using a non-parametric model to optimize prediction. High-contributing features were selected via k-means clustering of LRP results, forming a risk score model for RN vs. LR differentiation. The dataset included 142 BM lesions from 103 NSCLC patients, incorporating 3-month post-SRS T1+C MRI, seven genomic biomarkers, and seven clinical parameters. An 8:2 ratio was used for training and independent testing.

Results: Three high-contributing features, age(x1), ALK(x0.84) and PD-L1(x0.76) status, were identified by LRP and used to construct the risk score. The risk score model outperformed the model using all unweighted clinical/genomic features and an MR-only DNN. The HBNODE model, embedding the risk score within deep space, achieved the best performance across all metrics.

Conclusion: The derived risk score, based on non-imaging features, offers a simple and rapid indicator for distinguishing RN from LR. When integrated with MRI in the HBNODE model, it further enhanced predictive performance while maintaining high explainability, highlighting its potential as a clinical decision-aid tool for BM management.

Purpose: Escalating dose to the gross tumor volume (GTV) while de-escalating dose to the prostate clinical target volume (CTV) and using a 0-mm planning target volume margin can potentially minimize toxicity without compromising biochemical control in patients with intermediate-risk prostate cancer. We evaluated the technical feasibility of this approach in online adaptive magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy.

Methods and materials: The DESTINATION-MRL trial ran as 3 parallel single-center phase 2 non-randomized trials in 3 different institutes. Each institute enrolled 20 patients who were all treated on a 1.5T Unity MR-linear accelerator (MR-Linac). The GTV was defined as tumor(s) visible on multiparametric MRI. The CTV was defined as the whole prostate. The proximal 1-2 cm of the seminal vesicles were included in the CTV at the clinician's discretion. An intraprostatic margin of 4 mm was applied to the GTV to account for delineation and pathological uncertainty (GTV 4 mm) and no planning target volume margin was applied to the CTV. All patients were treated with 30 Gy in 5 fractions to the CTV and an isotoxic boost of 45 Gy to the GTV 4 mm. The primary endpoint was technical feasibility, defined as an accumulated GTV D90% of >42 Gy on the post-treatment MRI in ≥90% of the patients.

Results: Between May 2023 and September 2024, 60 patients were treated, of which 54 were included for analysis. An accumulated GTV D90% of >42 Gy was reached in 46 patients (85%). Analysis per institute showed that this criterion was reached in 10 of 14 patients (71%) in institute 1 and in 18 of 20 patients (90%) in both institutes 2 and 3.

Conclusions: Although toxicity-minimizing radiation therapy in online adaptive MRI-guided stereotactic body radiation therapy for prostate cancer was feasible in 2 of the 3 institutes, robust coverage of the GTV and CTV could not be assured in the absence of a gating strategy.

Purpose: To compare toxicities and oncological outcomes of postoperative sequential boost (Seq) versus simultaneous integrated boost (SIB) radiation therapy in extremity and trunk wall soft tissue sarcoma.

Methods and materials: This retrospective study compared postoperative Seq and SIB radiation therapy in 152 patients with extremity/trunk wall soft tissue sarcoma, analyzing clinicopathologic characteristics, major wound complications, Radiation Therapy Oncology Group (RTOG) late toxicity, and oncological outcomes (overall survival [OS], disease-free survival [DFS], local recurrence [LR], and distant metastasis) from a prospectively maintained database.

Results: Baseline characteristics (age, tumor location/site) were similar, but tumors were significantly larger in the SIB group (median 12.2 cm vs 7.4 cm; P = .007). Radiation therapy was delivered as Seq (66 Gy: 50 Gy/25 fractions + 16 Gy/8 fractions) or SIB (56/66 Gy in 33 fractions). Median follow-up was 5.3 years but was substantially longer for the Seq group (7.4 vs 3.4 years; P < .001). Major wound complications were comparable (Seq: 19.7% vs SIB: 17.9%; P = .91) with tumor size as the only significant factor (odds ratio, 1.08; P = .018). Late ≥G2 toxicities were similar: skin (23.2% vs 23.1%), subcutaneous fibrosis (37.2% vs 25.0%; P = .29), joint stiffness (7.0% vs 11.5%; P = .51), and edema (7.0% vs 13.5%; P = .50). One bone fracture occurred in the SIB cohort. Five-year LR was 3.1% (Seq) versus 2.4% (SIB). There were no significant differences in OS, DFS, LR, or distant metastasis. Multivariable analysis significantly linked age, tumor size, and grade 3 to OS, and tumor size and grade 3 to DFS.

Conclusions: Postoperative radiation therapy in soft tissue sarcoma using Seq or SIB appears to have similar toxicity and oncological outcomes, despite larger tumors in the SIB group. As SIB requires intensity modulated radiation therapy-which prior studies show reduces long-term adverse effects-it may be preferred, particularly in patients with larger treatment volumes undergoing postoperative radiation therapy.

Purpose: The impact of persistent hypogonadism post-androgen deprivation therapy (ADT) on overall survival (OS) of patients with prostate cancer (PCa) is poorly documented. We compared OS between patients who recovered testosterone and those who did not after ADT.

Methods and materials: Patients with PCa with intermediate- or high-risk disease were treated with ADT for 6, 18, or 36 months plus radiation therapy in 2 randomized trials. We compared OS between patients who recovered testosterone to a normal level to those who did not, using the log rank test. Multivariable Cox analysis to predict OS included recovered testosterone, age, Zubrod performance, comorbidities, baseline prostate specific antigen, Gleason score, stage, and ADT duration. To avoid immortal time bias, we performed a landmark analysis for each cohort.

Results: The median follow-up was 16.6 years. Patients not recovering testosterone to a normal level were older, with more associated medical comorbidities. All the results are reported respectively for the 6-, 18-, and 36-month ADT cohorts. Testosterone recovery rates, to normal level, were 76.7%, 58.6%, and 45.3% with a median time to testosterone recovery of 1.64, 3, and 5 years, respectively. The 10-year OS rates were significantly higher in patients recovering testosterone: 77% versus 61%, P < .001; 73% versus 51%, P < .001; and 78% versus 62%, P < .001. However, multivariable analyses with landmark time points failed to show testosterone recovery as an independent predictor. The study is limited by its post hoc analysis.

Conclusions: In patients with PCa, our study shows that persistent hypogonadism post-ADT is associated with worse survival, particularly in older patients with medical conditions.

Purpose: Radiation-induced optic neuropathy (RION) occurs in about 4% of extraocular tumors. Current predictive models reliably identify grade-4 RION when blindness is irreversible. We developed a sensitive multivariable Normal Tissue Complication Probability (NTCP) model integrating quantitative visual outcomes and dosiomics to predict earlier grade 2+ RION in a pencil beam scanning proton therapy cohort.

Methods and materials: This prospective study included patients with paraoptic head and neck cancer and patients with central nervous system tumor who underwent standardized ophthalmologic assessments at baseline and semiannually. Dosimetry for the optic nerves, chiasm, and retinas was analyzed. RION was defined as a visual field deficit below -6 dB (grade 2+). Predictive models-including logistic regression and random forest-were developed with multicollinearity reduction and stepwise feature selection to identify the most relevant predictors of RION.

Results: Of 238 patients, 105 had no/minor visual deficit before irradiation (179 eyes, median age 58.1 years) and were analyzed; 42/105 (23.5%) eyes developed grade 2+ RION over a 3.6-year median follow-up, with onset at 12.1 months. Lyman-Kutcher-Burman models had poor predictive value (area under the curve = 0.5). RION correlated with clinical features, including age (R = 0.24, P < .001, weak), hypertension (R = 0.23, P = .002, weak), cholesterol levels (R = 0.24, P = .004, weak), and baseline visual field mean deficit (R = -0.39, P < .001, moderate). Random forest models incorporating dosiomics achieved an area under the curve of 0.8. Baseline deficit (possibly by tumor compression/surgery) and optic chiasm volume receiving over 50Gy (V₅₀ chiasma) were the strongest predictors. Patients with minor baseline deficits were 3.29-fold higher risk to RION (95% CI, 2.87-3.38) more likely to develop RION than those without deficits. A V₅₀ chiasma above 50% was associated with 1.59 times (95% CI, 1.54-1.61) increased risk of RION compared to V₅₀ chiasma < 50 Gy. Female patients had higher NTCP than males (29.8% vs 21.0%; 95% CI, 25.0%-34.6% and 17.1%-24.9%, respectively). NTCP was also increased in patients with hypercholesterolemia (36.7%, 95% CI, 34.2%-39.3% vs 24.7%, 95% CI, 22.1-27.3) and hypertension (36.3%, 95% CI, 33.9%-38.7% vs 24.2%, 95% CI, 21.7-26.7).

Conclusions: Prospective and standardized visual assessment revealed a 23.5% risk of grade 2+ RION using visual field perimetry. Gender, vascular comorbidities, pre-existing damage from tumor compression or surgery to the optic pathways, and dose to the chiasma were risk factors for RION.

Purpose: Stereotactic body radiation therapy (SBRT) represents a novel, efficacious treatment for patients with kidney tumors who are medically inoperable or decline surgery. There is limited prospective data on the impact of kidney SBRT on renal function.

Methods and materials: This was a prospective phase 2 single-arm clinical trial (clinicaltrials.gov NCT03747133) of kidney-directed SBRT in patients with primary or metastatic renal lesions who were medically inoperable or declined surgery. The primary outcome was the change in kidney function, assessed by the change in eGFR (estimated glomerular filtration rate) over 2 years. The a priori hypothesis was that eGFR (mL/min/1.73 m²) does not decrease over time and was analyzed using a 1 sample t-test for noninferiority with a fixed margin of -6.974 based on published data at the time of trial design.

Results: Thirty patients with 32 renal tumors enrolled, with a median (IQR) age of 76 (73-82), a Charlson comorbidity index of 8 (7-9), 93% with chronic kidney disease stage ≥2 (eGFR ≤60 mL/min/1.73 m²), and the majority with cT1b disease with a median tumor size of 43 mm. Twenty-six patients (87%) had primary kidney cancer, and the remainder had metastatic lesions from non-kidney cancer histologies. Median radiation dose was 35 Gy in 5 fractions. Median follow-up was 24.5 months (IQR, 20-36.2). Median (IQR) eGFR levels (mL/min/1.73 m²) were 47.5 (37.8-64.0) at baseline, 42.0 (35.2-54.2) at 1 year, and 39.5 (25.5-54.8) at 2 years. Eighteen of 30 patients were evaluable for eGFR at 2 years. Noninferiority was not established based on a mean reduction in eGFR between baseline and 2 years of -8.7 mL/min/1.73 m² (95% 1-sided CI, -14.1, ∞; P = .71). Renal function decline was significantly associated with time, increasing age, baseline chronic kidney disease stages 3-4, and larger baseline tumor size on multivariable analysis. Local control was 96.7% at 2 years.

Conclusions: Kidney-directed SBRT results in modest clinical renal function loss up to 2 years following SBRT, based on evaluable patients in our study. Technical advances may further improve the therapeutic ratio.

Purpose: To validate a mechanistic Poissonian linear-quadratic tumor control probability model that incorporates tumor-volume heterogeneity, interpatient radiosensitivity variability, and treatment time effects using published breast cancer radiation therapy (RT) data sets.

Methods and materials: Local control (LC) data were obtained from the START A/B, FAST-Forward, and Early Breast Cancer Trialists' Collaborative Group studies. To address diverse scenarios, we combined data on the additive effect of adjuvant RT with outcomes from RT-alone treatments. We fitted the model parameters [α, β, α/β, σα (interpatient heterogeneity), tumor volume scaling, and exponential time-to-failure] against the observed LC rates. We quantified the effect of overall treatment duration on locoregional recurrence and estimated the residual clonogen count after surgery. We also predicted in-breast recurrence rates for various tumor sizes for neoadjuvant tumor-directed RT dose-fractionation schemes.

Results: The model reproduced 5-year LC outcomes across both adjuvant and RT-alone settings. The estimated residual clonogen count after surgery was 125. The calculated effect of overall treatment time for locoregional recurrence was 0.58 Gy/d, closely aligning with the 0.60 Gy/d estimate from the START trials. Simulations showed strong tumor-size dependence for preoperative stereotactic schedules: for a 5-mm diameter (T1a) tumor, the model predicted that a single 23-Gy fraction would result in >99.9% LC, whereas a 10-fraction regimen would yield ∼98% LC. For a 10-mm diameter tumor, single-fraction treatments maintained >98% LC. Control declined with increasing size, and no evaluated regimen achieved >90% LC for tumors >4 cm in diameter.

Conclusions: By incorporating tumor size heterogeneity, radiosensitivity variability, and time effect, the Poissonian linear-quadratic-based population tumor control probability model provides a robust framework for predicting LC in breast cancer RT. With further validation in larger data sets, this model could become a valuable tool to tailor dose regimens to individual patient and tumor characteristics, potentially improving LC rates and optimizing treatment strategies.

Purpose: Accelerated biological aging increases morbidity and mortality in patients with head and neck cancer (HNC) undergoing intensity modulated radiation therapy (IMRT). Stress from HNC and IMRT may exacerbate this process, yet the link between biological aging and perceived stress during treatment remains unclear. The purpose of this study was to examine associations between biological aging and perceived stress in HNC patients receiving IMRT across 4 time points: pre-IMRT, the end of IMRT, and 3 and 12 months post-IMRT.

Methods and materials: This prospective longitudinal study assessed perceived stress using the Perceived Stress Scale and various biological aging markers, including epigenetic age acceleration, Pace of Aging Calculated from the Epigenome (DunedinPACE), Klemera-Doubal biological age, phenotypic age (PhenoAge), homeostatic dysregulation, and inflammatory markers (interleukin [IL]-6, IL-1β, IL-10, IL-1ra, C-reactive protein, soluble tumor necrosis factor receptor (TNF) 2, and TNF-α). Linear mixed-effects models examined associations between each biological aging marker and perceived stress over time.

Results: Among 146 HNC patients (mean age ± SD, 59.12 ± 10.05 years; 73% male; 81% non-Hispanic White), perceived stress increased during treatment, declined significantly posttreatment, and remained lower than the baseline level. Higher perceived stress was significantly associated with increased DunedinPACE (estimate = 10.82; 95% CI, 4.49, 17.15; p = .001), Klemera-Doubal biological age (estimate = 0.03; 95% CI, 0.01, 0.05; p = .003), PhenoAge (estimate = 0.25; 95% CI, 0.06, 0.44; p = .011), C-reactive protein (estimate = 1.42; 95% CI, 0.35, 2.48; p = .009), TNF-α (estimate = -3.92; 95% CI, -7.53, -0.31; p = .033), and IL-1ra (estimate = 4.89, 95% CI, 2.24, 7.54; p < .001) over time, after adjusting for covariates (eg, age, sex, race, marital status, income, tumor human papillomavirus status, and treatment).

Conclusions: The strong association between biological aging and perceived stress suggests a critical role for stress in accelerating aging among patients with HNC. Future research should aim to investigate stress-inflammation management to decelerate aging and improve survival in these vulnerable cancer populations.