Assessment of minimum target dose as a predictor of local failure after spine SBRT.

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.

Automated target placement for VMAT lattice radiation therapy: enhancing efficiency and consistency.

Objective. An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMAT LRT) planning. These points are strategically placed within the gross tumor volume (GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk (OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance.Approach. A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives. These constraints encompassed minimum spacing between points, distance from OARs, and longitudinal separation along thez-axis. Additionally, the algorithm included an objective to permit, at the user's discretion, solutions with more centrally placed lattice points within the GTV. To validate its effectiveness, the automated approach was compared with manually planned treatments for 24 previous patients. Prior to clinical implementation, a failure mode and effects analysis (FMEA) was conducted to identify potential shortcomings.Main results.The automated program successfully met all placement constraints with an average execution time (over 24 plans) of 0.29 ±0.07 min per lattice point. The average lattice point density (# points per 100 c.c. of GTV) was similar for automated (0.725) compared to manual placement (0.704). The dosimetric differences between the automated and manual plans were minimal, with statistically significant differences in certain metrics like minimum dose (1.9% versus 1.4%), D5% (52.8% versus 49.4%), D95% (7.1% versus 6.2%), and Body-GTV V30% (20.7 c.c. versus 19.7 c.c.).Significance.This study underscores the feasibility of employing a straightforward Monte Carlo-based algorithm to automate the creation of spherical target structures for VMAT LRT planning. The automated method yields similar dose metrics, enhances inter-planner consistency for larger targets, and requires fewer resources and less time compared to manual placement. This approach holds promise for standardizing treatment planning in prospective patient trials and facilitating its adoption across centers seeking to implement VMAT LRT techniques.

Development and Assessment of a Predictive Score for Vertebral Compression Fracture After Stereotactic Body Radiation Therapy for Spinal Metastases.

IMPORTANCE: Vertebral compression fracture (VCF) is a potential adverse effect following treatment with stereotactic body radiation therapy (SBRT) for spinal metastases. OBJECTIVE: To develop and assess a risk stratification model for VCF after SBRT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study conducted at a high-volume referral center included 331 patients who had undergone 464 spine SBRT treatments from December 2007 through October 2019. Data analysis was conducted from November 1, 2020, to August 17, 2021. Exclusions included proton therapy, prior surgical intervention, vertebroplasty, or missing data. EXPOSURES: One and 3 fraction spine SBRT treatments were most commonly delivered. Single-fraction treatments generally involved prescribed doses of 16 to 24 Gy (median, 20 Gy; range, 16-30 Gy) to gross disease compared with multifraction treatment that delivered a median of 30 Gy (range, 21-50 Gy). MAIN OUTCOMES AND MEASURES: The VCF and radiography components of the spinal instability neoplastic score were determined by a radiologist. Recursive partitioning analysis was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was the criterion for node splitting. RESULTS: Of the 331 participants, 88 were women (27%), and the mean (IQR) age was 63 (59-72) years. With a median follow-up of 21 months (IQR, 11-39 months), we identified 84 VCFs (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median of 9 months (IQR, 3-21 months) to developing a VCF. From 15 candidate variables, 6 were identified using the backward selection method, feature importance testing, and a correlation heatmap. Four were selected via recursive partitioning analysis: epidural tumor extension, lumbar location, gross tumor volume of more than 10 cc, and a spinal instability neoplastic score of more than 6. One point was assigned to each variable, and the resulting multivariable Cox model had a concordance of 0.760. The hazard ratio per 1-point increase for VCF was 1.93 (95% CI, 1.62-2.30; P < .001). The cumulative incidence of VCF at 2 years (with death as a competing risk) was 6.7% (95% CI, 4.2%-10.7%) for low-risk (score, 0-1; 273 [58.3%]), 17.0% (95% CI, 10.8%-26.7%) for intermediate-risk (score, 2; 99 [21.3%]), and 35.4% (95% CI, 26.7%-46.9%) for high-risk cases (score, 3-4; 92 [19.8%]) (P < .001). Similar results were observed for freedom from VCF using stratification. CONCLUSIONS AND RELEVANCE: The results of this cohort study identify a subgroup of patients with high risk for VCF following treatment with SBRT who may potentially benefit from undergoing prophylactic spinal stabilization or vertebroplasty.

SBRT for HCC: Overview of technique and treatment response assessment.

Stereotactic body radiation therapy (SBRT) is an emerging locoregional treatment (LRT) modality used in the management of patients with hepatocellular carcinoma (HCC). The decision to treat HCC with LRT is evaluated in a multidisciplinary setting, and the specific LRT chosen depends on the treatment intent, such as bridge-to-transplant, down-staging to transplant, definitive/curative treatment, and/or palliation, as well as underlying patient clinical factors. Accurate assessment of treatment response is necessary in order to guide clinical management in these patients. Patients who undergo LRT need continuous imaging evaluation to assess treatment response and to evaluate for recurrence. Thus, an accurate understanding of expected post-SBRT imaging findings is critical to avoid misinterpreting normal post-treatment changes as local progression or viable tumor. SBRT-treated HCC demonstrates unique imaging findings that differ from HCC treated with other forms of LRT. In particular, SBRT-treated HCC can demonstrate persistent APHE and washout on short-term follow-up imaging. This brief review summarizes current evidence for the use of SBRT for HCC, including patient population, SBRT technique and procedure, tumor response assessment on contrast-enhanced cross-sectional imaging with expected findings, and pitfalls in treatment response evaluation.

Prediction of Tumor Control in 90Y Radioembolization by Logit Models with PET/CT-Based Dose Metrics.

The aim of this work was to develop models for tumor control probability (TCP) in radioembolization with 90Y PET/CT-derived radiobiologic dose metrics. Methods: Patients with primary liver cancer or liver metastases who underwent radioembolization with glass microspheres were imaged with 90Y PET/CT for voxel-level dosimetry to determine lesion absorbed dose (AD) metrics, biological effective dose (BED) metrics, equivalent uniform dose, and equivalent uniform BED for 28 treatments (89 lesions). The lesion dose-shrinkage correlation was assessed on the basis of RECIST and, when available, modified RECIST (mRECIST) at first follow-up. For a subset with mRECIST, logit regression TCP models were fit via maximum likelihood to relate lesion-level binary response to the dose metrics. As an exploratory analysis, the nontumoral liver dose-toxicity relationship was also evaluated. Results: Lesion dose-shrinkage analysis showed that there were no significant differences between model parameters for primary and metastatic subgroups and that correlation coefficients were superior with mRECIST. Therefore, subsequent TCP analysis was performed for the combined group using mRECIST only. The overall lesion-level mRECIST response rate was 57%. The AD and BED metrics yielding 50% TCP were 292 and 441 Gy, respectively. All dose metrics considered for TCP modeling, including mean AD, were significantly associated with the probability of response, with high areas under the curve (0.87-0.90, P < 0.0001) and high sensitivity (>0.75) and specificity (>0.83) calculated using a threshold corresponding to 50% TCP. Because nonuniform AD deposition by microspheres cannot be determined by PET at a microscopic scale, radiosensitivity values extracted here by fitting models to clinical response data were substantially lower than reported for in vitro cell cultures or for external-beam radiotherapy clinical studies. There was no correlation between nontumoral liver AD and toxicity measures. Conclusion: Despite the heterogeneous patient cohort, logistic regression TCP models showed a strong association between various dose metrics and the probability of response. The performance of mean AD was comparable to that of radiobiologic dose metrics that involve more complex calculations. These results demonstrate the importance of considering TCP in treatment planning for radioembolization.

Patient-reported financial toxicity and adverse medical consequences in head and neck cancer.

OBJECTIVES: Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT. MATERIALS AND METHODS: We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT. RESULTS: The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23-3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03-1.48), p = .02), and require supportive infusions (1.10 (1.02-1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14-2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment. CONCLUSION: HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care.

Effectiveness and cost of radiofrequency ablation and stereotactic body radiotherapy for treatment of early-stage hepatocellular carcinoma: An analysis of SEER-medicare.

INTRODUCTION: For early-stage hepatocellular carcinoma (HCC) patients, ablative strategies are potentially curative treatment options. Stereotactic body radiotherapy (SBRT) has emerged as a promising ablative therapy, although its comparison with radiofrequency ablation (RFA) remains confined to a single institution retrospective review. We sought to characterize the comparative outcomes and cost between the two treatment strategies. METHODS: We conducted a secondary analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (2004-2011) and identified adult patients with stage I or II HCC and treated with RFA or SBRT as the initial treatment within 6 months of diagnosis. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox proportional hazard analysis. Factors associated with overall survival and 90-day hospital admission post-treatment were identified using propensity score (PS) adjusted multivariate analysis. We performed costs analysis and calculated incremental cost-effectiveness ratios (ICER). RESULTS: Four hundred and forty patients were identified, 408 treated with RFA and 32 SBRT. In the overall cohort, 90-day hospitalization and 1-year mortality were similar between groups but RFA patients had better overall survival (P < 0.001). Multivariate analysis showed advanced age, higher stage, decompensated cirrhosis, and treatment with SBRT (HR 1.80; 95%CI: 1.15-2.82) was associated with worse survival, but in the PS adjusted analysis, survival and costs were similar between the two groups. CONCLUSION: In a national cohort of early stage HCC patients, treatment with RFA vs SBRT resulted in no significant difference in survival, 90-day hospitalization, or costs. These data highlight the need for a randomized clinical trial comparing these two modalities.