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.

Proton versus photon craniospinal irradiation for adult medulloblastoma: A dosimetric, toxicity, and exploratory cost analysis.

Background: This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients. Methods: This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients. Results: Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18-66). The molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all P < .001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% versus 35%, P = .044) and decreased median weight loss during radiation (+1.0 versus -2.8 kg, P = .011). Weight loss was associated with acute hospitalization (P = .009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At the last follow-up, 5 photon patients had died (2 of progressive disease, 3 without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free. Conclusions: This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.

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.

Brain metastases resection cavity radio-surgery based on T2-weighted MRI: technique assessment.

PURPOSE: Stereotactic radiosurgery (SRS) is commonly performed after surgical resection of brain metastases to reduce the chance of local tumor recurrence while maintaining cognitive function. Target delineation in these cases is typically based off T1-weighted post-gadolinium MRI (T1Gd). In this study, we report outcomes for patients having postoperative SRS in which the planning target volume (PTV) was based on T2-weighted MRI (T2W). METHODS: Sixty-two consecutive patients having single-fraction SRS after brain metastases resection were retrospectively reviewed. Excluded were patients with prior whole brain radiation therapy, multiple resection cavities, and small cell pathologies. RESULTS: The median time from surgery to SRS was 11 days; 26 patients (42%) had SRS ≤ 7 days. The median PTV was 8.0 cm3; the median margin dose was 18 Gy. The crude rates of local tumor control (LC), leptomeningeal disease (LMD), distant brain recurrence (DBR), and radiation necrosis (RN) were 85%, 19%, 37%, and 2%, respectively. The 1-year LC, LMD, DBR, and RN rates were 88%, 25%, 36%, and 0%, respectively. No tumor or dosimetric factor was associated with LC. Sub-total tumor resection was a risk factor for LMD (HR 5.11, P = 0.003), whereas patients with multiple brain metastases had a greater risk of DBR (HR 2.88, P = 0.01). The median PTV was smaller compared to the median PTV based off the consensus guidelines utilizing T1Gd MRI (8.0 cm3 vs. 9.1 cm3, P = 0.004). CONCLUSION: T2W MRI provided accurate resection cavity delineation even in the early postoperative period and was associated with decreased PTV compared to T1Gd MRI in the majority of cases.

Impact of Patient Stage and Disease Characteristics on the proposed Radiation Oncology Alternative Payment Model (RO-APM).

PURPOSE: The proposed Radiation Oncology Alternative Payment Model (RO-APM) released on July 10, 2019, represents a dramatic shift from fee-for-service (FFS) reimbursement in radiation therapy (RT). This study compares historical revenue at Mayo Clinic to the RO-APM and quantifies the effect that disease characteristics may have on reimbursement. METHODS AND MATERIALS: FFS Medicare reimbursements were determined for patients undergoing RT at Mayo Clinic from 2015 to 2016. Disease categories and payment episodes were defined as per the RO-APM. Average RT episode reimbursements were reported for each disease site, except for lymphoma and metastases, and stratified by stage and disease subcategory. Comparisons with RO-APM reimbursements were made via descriptive statistics. RESULTS: A total of 2098 patients were identified, of whom 1866 (89%) were categorized per the RO-APM; 840 (45%) of those were aged >65 years. Breast (33%), head and neck (HN) (14%), and prostate (11%) cancer were most common. RO-APM base rate reimbursements and sensitivity analysis range were lower than historical reimbursement for bladder (-40%), cervical (-34%), lung (-28%), uterine (-26%), colorectal (-24%), upper gastrointestinal (-24%), HN (-23%), pancreatic (-20%), prostate (-16%), central nervous system (-13%), and anal (-10%) and higher for liver (+24%) and breast (+36%). Historical reimbursement varied with stage (stage III vs stage I) for breast (+57%, P < .01), uterine (+53%, P = .01), lung (+50%, P < .01), HN (+24%, P = .01), and prostate (+13%, P = .01). Overall, for patients older than 65 years of age, the RO-APM resulted in a -9% reduction in total RT reimbursement compared with historical FFS (-2%, -15%, and -27% for high, mid, and low adjusted RO-APM rates). CONCLUSIONS: Our findings indicate that the RO-APM will result in significant reductions in reimbursement at our center, particularly for cancers more common in underserved populations. Practices that care for socioeconomically disadvantaged populations may face significant reductions in revenue, which could further reduce access for this vulnerable population.

Biologic Dose and Imaging Changes in Pediatric Brain Tumor Patients Receiving Spot Scanning Proton Therapy.

PURPOSE: To evaluate the incidence of imaging changes in our pediatric brain tumor population treated with spot-scanning proton therapy and analyze the spatial correlation of imaging changes with a novel biologic dose model. METHODS AND MATERIALS: All pediatric patients treated during the first year of our institution's experience who received a minimum treatment planning dose (TPD) of 5040 cGyE with available follow-up magnetic resonance imaging scans were selected for analysis. Posttreatment magnetic resonance imaging scans were fused with the treatment planning computed tomography. All T1 post-gadolinium enhancement, T2 fluid attenuated inversion recovery changes, TPD, and biologic dose (BD) volumes outside of the original gross tumor volume were contoured for analysis. RESULTS: Thirty patients were included in the analysis, 7 of whom developed posttreatment radiologic changes. The volumetric overlap of the T2 fluid attenuated inversion recovery changes and BD volumes was significantly greater than the overlap with the TPD volumes. Median volumetric overlaps of 85%, 18%, and 0% were observed with the BD105%, BD110%, and TPD105%, respectively. A nonsignificant increase in the volumetric overlap of the T1C+ changes and BD volumes was also observed. No correlation was observed between the total volume of BD110%, BD105%, or physical dose 105% and the development of imaging changes. CONCLUSIONS: Within our pediatric brain tumor population treated with spot-scanning proton therapy, our BD model demonstrated superior volumetric overlap with posttreatment T2 changes compared with the TPD model. Using a BD model in treatment planning for spot-scanning proton therapy may help avoid delivery of excessive BD to critical structures and may help minimize the risk of radiation-related late effects.

Proton therapy for pediatric malignancies: Fact, figures and costs. A joint consensus statement from the pediatric subcommittee of PTCOG, PROS and EPTN.

Radiotherapy plays an important role in the management of childhood cancer, with the primary aim of achieving the highest likelihood of cure with the lowest risk of radiation-induced morbidity. Proton therapy (PT) provides an undisputable advantage by reducing the radiation 'bath' dose delivered to non-target structures/volume while optimally covering the tumor with tumoricidal dose. This treatment modality comes, however, with an additional costs compared to conventional radiotherapy that could put substantial financial pressure to the health care systems with societal implications. In this review we assess the data available to the oncology community of PT delivered to children with cancer, discuss on the urgency to develop high-quality data. Additionally, we look at the advantage of combining systemic agents with protons and look at the cost-effectiveness data published so far.

Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data.

The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM. However, contrary to this view, overwhelming clinical evidence demonstrates that there is also a clinically significant tumor burden with an intact BBB in all GBM, and there is little doubt that drugs with poor BBB permeability do not provide therapeutically effective drug exposures to this fraction of tumor cells. This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated.

Clinical Implementation of a Proton Dose Verification System Utilizing a GPU Accelerated Monte Carlo Engine.

PURPOSE: To develop a clinical infrastructure that allows for routine Monte Carlo dose calculation verification of spot scanning proton treatment plans and includes a simple biological model to aid in normal tissue protection. MATERIALS AND METHODS: A graphical processing unit accelerated Monte Carlo dose engine was used as the calculation engine for dose verification on spot scanning proton plans. An infrastructure was built around this engine that allows for seamless exporting of treatment plans from the treatment planning system and importing of dose distribution from the Monte Carlo calculation via DICOM (digital imaging and communications in medicine). An easy-to-use Web-based interface was developed so that the application could be run from any computer. In addition to the standard relative biological effectiveness = 1.1 for proton therapy, a simple linear equation dependent on dose-weighted linear energy transfer was included. This was used to help detect possible high biological dose in critical structures. RESULTS: More than 270 patients were treated at our proton center in the first year of operation. Because most plans underwent multiple iterations before final approval, more than 1000 plans have been run through the system from multiple users with minimal downtime. The average time from plan export to importing of the Monte Carlo doses was less than 15 minutes. Treatment plans have been modified based on the nominal Monte Carlo dose or the biological dose. CONCLUSION: Monte Carlo dose calculation verification of spot scanning proton treatment plans is feasible in a clinical environment. The 3-dimensional dose verification, particularly near heterogeneities, has resulted in plan modifications. The biological dose data provides actionable feedback for end of range effects, especially in pediatric patients.

Exploring primary brain tumor patient and caregiver needs and preferences in brief educational and support opportunities.

PURPOSE: A primary brain tumor patient and caregiver survey was completed to investigate interest in brief support opportunities, focused on education, memory training, and healthy coping, during a routine clinical visit and at 3-month follow-up. METHODS: Patients with primary brain tumors receiving care in the Radiation Oncology Department at Mayo Clinic Rochester and their caregivers were recruited to complete the survey between June 2008 and September 2009. RESULTS: Both patients and their caregivers expressed greatest interest in education about brain tumors and cognitive effects of treatment. Interest in support opportunities targeting education, memory training, or healthy coping was low to modest. Bimodal distributions were found for almost all the support opportunities, revealing subgroups of patients and caregivers with high interest in such sessions. Overall, ratings of interest did not differ over time. CONCLUSIONS: Patients with primary brain tumors and their caregivers expressed most interest in education about their disease and potential cognitive effects of treatment. It appears that subgroups of patients and caregivers have very high interest in brief support opportunities. Identifying these subgroups of patients and families will allow targeted interventions focused on their needs and make the best use of limited resources.