Prescription Isodose Line Research Articles

Safety and efficacy of silibinin in patients with brain metastases after stereotactc radiosurgery: SUSTAIN trial.

e14012 Background: Brain metastases (BMs) account for more than one-half of all intracranial tumors. Over the past years, stereotactic radiosurgery (SRS) has become the mainstay of BMs treatment, providing high rates of local tumor control. Nevertheless, SRS alone is associated with a 30-50% risk of distant brain failure (DBF), consequently requiring careful follow-up and possible rescue treatments. Silibinin or silybin, a natural polyphenolic flavonoid, has shown promising antitumor activity, leading to improvement of BMs in patients (pts) with progressive non-small cell lung cancer. Therefore, our exploratory study aims to evaluate whether the use of a silibinin-based nutraceutical can significantly reduce DBF rate at 6 months in pts with first-diagnosed BMs treated with SRS with or without surgery. Methods: SUSTAIN is an interventional, prospective, single arm, phase II study. A total of 80 pts treated in our center are planned to be enrolled. Pts receive 2 capsules (cps) of silibinin-based nutraceutical per day for the first month after SRS and 1 cp per day thereafter. Primary endpoints are 6-month distant brain failure (DBF) rate and safety; secondary endpoint is 6-month overall survival (OS) rate. Contrast-enhanced magnetic resonance (MRI) of the brain is performed at baseline and every 12 weeks after SRS treatment; radiological response is assessed according to RANO criteria for brain metastases (RANO-BM). Results: Thirty pts has been enrolled at the time of this primary analysis (Tab1). NSCLC and breast cancer were the prevalent histologies (14 and 10 cases respectively). Twelve pts were chemotherapy naive at the time of BMs diagnosis; 10 pts has received 1 systemic therapy line and 8 pts has received 2 lines or more. Overall, the number of treated lesions was 73, with a median of 1 lesion (range 1-9). All pts underwent SRS (Fig.1), with a median prescription dose (PD) and a median prescription isodose line (IDL) of 24 Gy and 80% respectively. After a 14-month enrollment period, with a median follow-up of 9 months, 6 pts reported distant intracranial failure according to RANO-BM criteria, with a 6-month DBF rate of 20%. Only 1 treated lesion met the criteria for progression, accounting for a 6-month local control (LC) rate of 98%. Six pts died, with a 6-month OS rate of 80%. Radiological radionecrosis was detected in 3 pts (10%), who developed G1 neurological symptoms managed with low-dose dexamethasone. Two pts discontinued silibinin-based nutraceutical assumption due to G1 nausea. No other adverse events were reported. Conclusions: At about half of our enrollment target, the results show a favorable trend towards 6-month DBF rate reduction. Toxicity proved manageable, consistent with the literature and limited to gastrointestinal effects. A larger sample and longer follow-up is needed to confirm our hypothesis.

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study.

Stereotactic body radiotherapy (SBRT) has proven to provide high rates of tumor control for patients with early-stage non-small cell lung cancer (NSCLC). We are reporting a multicenter experience of long-term clinical outcomes and adverse effect profiles of patients with medically inoperable early-stage NSCLC treated with SBRT. A total of 145 early-stage NSCLC patients underwent SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Shandong Cancer Hospital and Institute, and Shanghai Pulmonary Hospital between October 2012 and March 2019. Four-dimensional computed tomography (4D-CT) simulation was used for all patients. All received a biologically effective dose (BED; α/β=10) of 96-120 Gy with the prescribed isodose line covering >95% of the planning target volume (PTV). Survival was analyzed by the Kaplan-Meier method. Survival was estimated using the Kaplan-Meier method. The median tumor diameter was 2.2 (range, 0.5-5.2) cm. The median follow-up was of 65.6 months. Thirty-five patients (24.1%) developed disease recurrence. The rates of local, regional, and distant disease recurrence were, respectively, 5.1%, 7.4%, and 13.2% at 3 years; and 9.6%, 9.8%, and 15.8% at 5 years. Progression-free survival (PFS) rates at 3 and 5 years were 69.2% and 60.5% respectively; the overall survival (OS) rates were 78.1% and 70.1%, respectively. Five patients (3.4%) experienced grade 3 treatment-related adverse events (AEs). No patient experienced grade 4 or 5 toxicity. From our retrospective analysis with long-term follow-up in Chinese population, SBRT achieved high rate of local control (LC) and low toxicity in patients with early-stage NSCLC. This study offered robust long-term outcome data of SBRT in the Chinese population, which was very rarely reported in China before.

Abstract PD3-06: Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial

Abstract Purpose: Outcomes following adjuvant accelerated partial breast irradiation (APBI) in select women with early-stage breast cancer are comparable to whole breast irradiation. Robotic stereotactic accelerated partial breast irradiation (RSAPBI) with fiducial tracking is an attractive treatment option, but limited outcomes data are available for this approach. We report 2-year outcomes for a prospective multi-institutional trial treating select women with RSAPBI. Materials and Methods: Post-menopausal women with DCIS and Stage IA breast cancer were treated over a five-year period extending from November 2015 to November 2020 and were followed for a minimum of 18 months. Treatments were delivered with a robotic radiosurgery system. Four gold fiducials were implanted around the lumpectomy cavity prior to the start of treatment for tumor bed delineation and target tracking. The CTV was defined as the lumpectomy cavity with a uniform 5-15 mm expansion confined to the breast tissue and the PTV was defined as the CTV with a 0-5 mm uniform expansion. The PTV was prescribed 30 Gy in 5 fractions. Disease status assessments were completed at 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months and yearly intervals thereafter for five years. Results: Eighty-one patients (median age 68 years) with hormone receptor-positive tumors were treated over a median 9 days (range, 5-15). Sixty-eight women had invasive ductal carcinoma (84%) and thirteen had DCIS (16%). The median treated PTV was 108 cm3 (IQR 66-156) and the median prescription isodose line was 81% (IQR 79-83). The median CTV expansion was 10 mm (range 5-10) and the median PTV expansion was 3 mm (range 0-5). At a median follow up of 2 years there was one new ipsilateral breast tumor diagnosed. There were no local, regional, or distant treatment failures. Conclusions: Two-year results suggest that RSAPBI with fiducial tracking is an effective technique for the adjuvant treatment of post-menopausal women with hormone receptor-positive early-stage breast cancer. Additional follow-up is planned to confirm this preliminary finding. Citation Format: Jonathan M. Cantalino, David D’Ambrosio, Arica Hirsch, Brian Collins, Malika Danner, Dawn Matsanka, Sonali Rudra, Simeng Suy, Sean Collins, Monica Pernia Marin, Michael Good, Jing Feng, John Lamond, Deborah Markiewicz, Rachelle Lanciano, Olusola Obayomi-Davies. Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-06.

Analysis of CyberKnife intracranial treatment plans using ICRU 91 dose reporting: A retrospective study.

ICRU 91, published in 2017, is an international standard for prescribing, recording, and reporting stereotactic treatments. Since its release, there has been limited research published on the implementation and impact of ICRU 91 on clinical practice. This work provides an assessment of the recommended ICRU 91 dose reporting metrics for their use in clinical treatment planning. A set of 180 intracranial stereotactic treatment plans for patients treated by the CyberKnife (CK) system were analyzed retrospectively using the ICRU 91 reporting metrics. The 180 plans comprised 60 trigeminal neuralgia (TGN), 60 meningioma (MEN), and 60 acoustic neuroma (AN) cases. The reporting metrics included the planning target volume (PTV) near-minimum dose ( ), near-maximum dose ( ), and median dose ( ), as well as the gradient index (GI) and conformity index (CI). The metrics were assessed for statistical correlation with several treatment plan parameters. In the TGN plan group, owing to the small targets, was greater than in 42 plans, whereas both metrics were not applicable in 17 plans. The metric was predominantly influenced by the prescription isodose line (PIDL). The GI was significantly dependent on target volume in all analyses performed, where the variables were inversely related. The CI was only dependent on target volume in treatment plans for small targets. The ICRU 91 and metrics breakdown in plans for small target volumes below 1 cm3 ; the Min and Max pixel should be reported in such cases. The metric is of limited use for treatment planning. Given their volume dependence, the GI and CI metrics could potentially serve as plan evaluation tools in the planning of the sites analyzed in this study, which would ultimately improve treatment plan quality.

Dose Prescription to Isodose Lines in Static Multi-Beam Stereotactic Body Radiotherapy for Lung Tumors: Which Line Is Optimal?

This study investigated the appropriate dose prescription method in static multi-beam stereotactic body radiotherapy for lung tumors. Static multi-beam stereotactic body radiotherapy is a mainstream treatment in Japan. Based on the hypothesis that dose prescription to lower isodose lines may improve planning target volume dose coverage and decrease doses to organs at risk, we investigated changes in dose-volume histograms with prescription to various isodose lines for planning target volume in static multi-beam stereotactic body radiotherapy. In all treatment plans, 45 Gy in 4 fractions were prescribed to 95% of the planning target volume. By adjusting the leaf margins of each beam, various prescription isodose lines encompassing 95% volume of the planning target volume were generated. The prescription isodose lines investigated were 40, 50, 60, 70, 80 and 90% lines relative to the maximum dose of each planning target volume. The conformity index, homogeneity index, mean lung dose, and V5-V40 of the lung were evaluated. The dose was calculated by the adaptive convolve algorithm. The conformity index was lowest in the 70% or 80% isodose plan. The mean lung doses and V10-V40 of the lung decreased steeply from the 90% to the 70% isodose plan, and was lowest in the 60% and 70% isodose plans. These indices increased in the 40% and 50% isodose plans. The optimal stereotactic body radiotherapy plans appeared to be dose prescription to the 60% or 70% isodose line. Further investigation is warranted to clarify the advantage of using this method clinically.

Patterns of Failure Following Stereotactic Radiosurgery Salvage for Recurrent High-Grade Glioma

<h3>Purpose/Objective(s)</h3> Stereotactic radiosurgery (SRS) is an increasingly used treatment for patients with progressive high-grade glioma (HGG). We sought to determine which demographic and clinical factors are associated with pattern of recurrence and outcome following SRS to better predict which patients would benefit from local salvage. <h3>Materials/Methods</h3> This retrospective analysis of a prospectively maintained database included continuous patients treated with SRS salvage at a single institution between January 2008 and May 2020. Patterns of failure were classified according to the distance from the prescription isodose line. Local failures included in-field (within the prescription isodose line), marginal (< 2 cm), and regional (2-5 cm). Distant failures were > 5 cm. Survival was estimated using Kaplan-Meier methods. The Wilcoxon rank-sum test, Kruskal-Wallis test, and Spearman correlations were used to examine associations between patterns of failure and demographic and clinical variables at first failure. Multilevel mixed-effects parametric regressions were used to identify predictors of SRS failure. <h3>Results</h3> One hundred forty-eight patients (males, 56.8%; non-Hispanic White, 72.3%) ages 20 to 83 years (median, 58 years) with HGG (WHO Grade IV, 92.6%) underwent salvage to a total of 412 targets. The median (interquartile range) size of target was 3.4 (1.0-8.7) cm³. The median dose was 18 (16-20) Gy. The median time from diagnosis to salvage was 12.1 (7.6-19.3) months. With a median follow up of 8.2 months, 62 (41.9%) patients developed progression following SRS. Progression-free survival at 6 and 12 months were 64.4% (95% confidence interval [CI]: 55.7-71.7) and 36.8% (95% CI: 28.7-45.0), respectively. Fifty (80.7%) patients developed local, two (3.2%) distant, and 10 (16.1%) concomitant local and distant failure. Actuarial local control at 6 and 12 months were 80.8% (95% CI: 72.4-86.8) and 61.8% (95% CI: 51.4-70.7), respectively. Of 60 local failures, 31 (51.7%) were in-field, 25 (41.7%) marginal, and four (6.7%) regional. Median overall survival was 26.6 months from diagnosis and 13.0 months from first GK treatment. Non-White race (HR = 0.32, 95% CI: 0.15-0.66) and GK dose (HR = 0.87, 95% CI: 0.79-0.95, P = 0.002) were independent predictors of SRS failure. Non-White race (r_s = .31, P = 0.012) and GK target size (X² (3, N = 62) = 10.09, P = 0.017) were positively associated with a more distant pattern of failure. Age at diagnosis, sex, and glioma grade were not associated (P > 0.05) with GK failure or pattern of failure. No Grade 4 or 5 toxicity was observed. <h3>Conclusion</h3> SRS salvage is a safe and effective treatment for select patients with progressive HGG. The dominant pattern of failure following salvage was local; approximately half of local progressions were in-field. Higher dose decreased the hazard for progression, indicating that some patients may benefit from dose escalation.

Study of Linear Energy Transfer Effect on Rib Fracture in Breast Patients Receiving Pencil-Beam-Scanning Proton Therapy

<h3>Purpose/Objective(s)</h3> To study the linear energy transfer (LET) effect upon rib fracture (RF) in breast cancer patients treated with pencil-beam scanning proton therapy (PBS) using dose-linear energy transfer volume histogram (DLVH). <h3>Materials/Methods</h3> After IRB approval, we retrospectively identified RF cases detected after workup of chest wall pain or incidentally on imaging in breast cancer patients treated with PBS to the breast/chest wall and regional nodes from 2015-2020. Control patients were selected to match the RF patients 2:1 considering prescription dose, boost location, reconstruction status, laterality, chest wall thickness, and treatment year. For all plans, a chest wall was contoured, incorporating ribs and intercostal muscles within the 50% prescription isodose line. Both dose and LET were calculated using a planning tool dose engine. DLVH was generated for each patient, using dose and LET as the two axes. The DLVH index, <i>V</i>(<i>d, l</i>), defined as <i>V</i>(% for normalized volume or cc for absolute volume) of the structure with a dose of at least <i>d</i> Gy[RBE] and an LET of at least <i>l</i> keV/µm, was calculated for all combinations of <i>d</i> and <i>l</i>. Conditional logistic regression model was used to establish the relation of <i>V</i>(<i>d, l</i>) and the observed RF at each combination of <i>d</i> and <i>l</i>. The derived <i>p values</i> constitute a <i>p value</i> map in the 2D dose and LET plane. Concordance and its standard error (se) maps were generated to evaluate the performances for all DLVH indices. A correlation coefficient map was obtained to determine the correlation between the featured DLVH indices. <h3>Results</h3> Eight RF cases were identified, and 16 controls were matched. Of RF patients, seven were treated with post-mastectomy (PMRT) and one was treated with post-lumpectomy radiotherapy. Six RF patients treated with PMRT received a dose of 50 Gy[RBE] in 25 fractions to the chest wall and regional lymph nodes; of these, four received a simultaneous integrated boost (SIB) of 56.25 Gy[RBE] to the chest wall (n=2) or axillary nodes (n=2), and one received a sequential boost of 14 Gy[RBE] in 7 fractions to the chest wall. One RF patient that received PMRT was treated with 40.05 Gy[RBE] in fifteen fractions to the chest wall and regional lymphatics. The post-lumpectomy patient received 50 Gy[RBE] in 25 fractions to the whole breast and regional nodes with a SIB of 56.25 Gy[RBE] to the lumpectomy cavity. Two characteristics correlated with RF (<i>p</i><0.2): 1) Smaller <i>V</i>(50-54 Gy[RBE], 0-4.4keV/µm) of the RF patients with a maximum concordance of 0.813 (se 0.114); 2) Larger <i>V</i>(0-36 Gy[RBE], 5.2-6.8keV/µm) of the RF patients with a maximum concordance of 0.875 (se 0.119) compared with controls. These two features were independent from each other with a weak negative correlation (-0.185). <h3>Conclusion</h3> The increase of high LET in moderate dose regions of the chest wall from constraining the adjacent heart and lung dose during PBS treatment planning may result in increased risk of RF.

Frameless Fractionated Stereotactic Radiosurgery for Brain Metastases: An Institutional Series of 89 Cases

<h3>Purpose/Objective(s)</h3> Cobalt-60 stereotactic radiosurgery (SRS) conventionally involves frame-based immobilization and single-fraction treatment. However, certain anatomical and technical factors, including large lesion size, close proximity to critical structures, and prior radiation treatment, necessitate fractionated SRS, which requires mask-based immobilization. We present a large institutional experience with mask-based fractionated SRS for large, retreated, or critically-located brain metastases. <h3>Materials/Methods</h3> All patients treated with frameless fractionated SRS for brain metastases between March 2017 and August 2021 at a single institution were identified. Patient, tumor, and treatment variables were abstracted. The primary outcome was one-year local control (LC), which was analyzed with the Kaplan-Meier method. This study was approved by the institution's IRB. <h3>Results</h3> Seventy-four patients with a total of 89 brain metastases were treated. The median follow-up time was seven months. The median age at treatment was 64 years. Sixty-two percent of patients were female. The most common primary tumors were breast (24.7%), non-small cell lung (24.7%), small-cell lung (7.9%), renal cell (6.7%), and melanoma (6.7%). For the majority (62.9%) of tumors, the indication for fractionation was retreatment; other indications were large size (21.3%), critical location (12.4%), and medical comorbidity (3.4%). For all tumors, the mean maximal linear size was 35.5 mm; for tumors fractionated due to size, the mean size was 45.8 mm. The median total dose was 2,750 cGy (range: 1,620-3,000), and the median dose per fraction was 600 cGy (range: 405-900); the most common dose-fractionations were 3,000 cGy in 600 cGy per fraction (42.7% of patients) and 2500 cGy in 500 cGy per fraction (31.5% of patients). The mean target volume was 17.6 cc (range: 0.13-120.0), and the mean maximum dose was 4,980 cGy (range: 3,240-6,000). For 91% of treatments, the prescription isodose line was 50 to 59% (mean, 54%). Target coverage was 100% in all but one case, where it was 99%. For lesions near the brainstem, mean brainstem maximum point dose (MPD) was 9.78 Gy and mean brainstem mean dose was 3.56 Gy. For lesions near the optic pathway, mean optic nerve MPD was 14.39 Gy, mean optic nerve mean dose was 6.2 Gy, mean optic chiasm MPD was 11.7 Gy, and mean optic chiasm mean dose was 5.4 Gy. LC at 12 months was 91%. Nineteen percent of patients experienced acute grade 1-2 toxicity; one patient experienced acute grade 3 fatigue, and there was no other grade 3 or higher acute toxicities. Seventeen percent of patients had grade 1-2 radiation necrosis (RN); there were no cases of grade 3 or higher RN. <h3>Conclusion</h3> Cobalt-60 frameless fractionated SRS for brain metastases offers excellent local control. This treatment modality is technically feasible, offers excellent sparing of critical structures, and has minimal toxicity. Frameless fractionated SRS should be considered for large, retreated, or critically located metastases.

Single-Fraction vs. Fractionated Radiosurgery and the Development of Post-Treatment Hemorrhage for Intact Melanoma Brain Metastases

<h3>Purpose/Objective(s)</h3> To assess whether intracranial stereotactic radiotherapy fractionation is associated with increased risk of post-treatment lesional hemorrhage in patients with intact melanoma brain metastases (MBM). <h3>Materials/Methods</h3> A single institution retrospective review was performed of patients with previously unresected MBM treated with robotic SRS/fSRT between 2013 to 2021. The presence of lesional hemorrhage was determined by multi-disciplinary neuroradiology review of magnetic resonance imaging (MRI). Dosimetric variables were reported as biologically effective doses using an estimated α/β ratio of 2.5 (BED_2.5) for melanoma to permit comparison across varying fractionation schedules. The effect of fractionation and additional prognostic factors on the rate of post-treatment development of hemorrhage was statistically analyzed using logistic regression with random effects to account for interactions between lesions of the same patient. A Cox model was used for local control (LC) with a frailty term to account for dependence between lesions. <h3>Results</h3> The cohort included 48 patients with 226 intact MBM treated with SRS/fSRT. Evidence of hemorrhage prior to treatment was demonstrated in 69 of 226 metastases (30.5%). For lesions without signs of prior hemorrhage, 65 of 157 (41.4%) demonstrated evidence of hemorrhage after radiosurgical treatment. 63 of 133 lesions (47.4%) receiving single-fraction SRS demonstrated evidence of post-treatment hemorrhage versus 2 of 24 lesions (8.3%) treated with fSRT (<i>p=0.01</i>). Treatment factors including lesion size, prescription isodose line, as well as receipt of corticosteroids, targeted, or immune therapy were not predictive of hemorrhage occurrence. A larger maximum BED_2.5 was observed in lesions developing hemorrhage compared to no hemorrhage (mean 238.3 Gy vs. 211.4 Gy; <i>p=0.022</i>). LC at twelve-months was 65.7% (95% CI 37.2-87.3%) and 77.5% (95% CI 58.5-91.2%) for lesions demonstrating pre-treatment and post-treatment hemorrhage, respectively, with no local failure events observed in non-hemorrhagic lesions (<i>p=<0.001</i>). <h3>Conclusion</h3> Intact MBM without prior evidence of hemorrhage receiving single-fraction SRS were associated with an increased incidence of post-treatment hemorrhage when compared to those treated with fractionated stereotactic radiotherapy. The presence of lesion hemorrhage, either pre- or post-treatment, was associated with inferior local control. Post-treatment hemorrhage was correlated with a larger maximum BED_2.5. Further investigations of the clinical impact of lesional hemorrhage, factors influencing lesion control, as well as optimal dose and fractionation schedules for treatment of MBM in the era of immunotherapy are warranted.

Tumor Size and Dose Impact Recurrence after Stereotactic Body Radiotherapy (SBRT) for Liver Metastases (LM) from Colorectal Cancer (CRC)

<h3>Purpose/Objective(s)</h3> SBRT is used to treat LM from CRC. Prior studies demonstrate acceptable in-field control (IFC) but have limited evaluation of treatment characteristics. We sought to determine the effect of tumor and treatment-related variables. <h3>Materials/Methods</h3> We reviewed an IRB-approved prospectively collected database of SBRT treatments between 2013-2021 at an NCI-designated comprehensive cancer center. Post-SBRT MRI every 3-4 months was fused with RT plan and evaluated for in-field (IFR), marginal (MR), and regional (RR) liver recurrences. MR = low dose region adjacent to high dose region. RR = elsewhere in liver. Retreated lesions were excluded. Tumor and dosimetric variables were compared by lesion recurrence status using Wilcoxon rank sum tests and Fisher exact tests. IFC (time to IFR) and IFC/MC (time to IFR or MR) were evaluated using Kaplan Meier methods with log rank tests and/or Cox proportional hazards methods using within-patient robust standard errors. <h3>Results</h3> The study included 33 patients with 41 lesions. Most (72%) were metastatic at presentation and had a single lesion treated (n=25), while the remaining had 2 treated simultaneously (n=5) or sequentially (n=3). Median age was 59 years (34-88). Median tumor volume was 35.5 cc, with 25 (61%) from 10 to 50 cc. Median total dose (TD) was 55 Gy (24-60 Gy) in 5 fractions (3-5); 19 lesions (46%) received 60 Gy. Median follow-up was 18.4 months in those who died (n=10) and 20.2 in those alive (n=13). IFR and MR were diagnosed in 7 (17%) and 4 (9%) lesions, respectively. Nineteen (46%) had RR. 1-year IFC was 86% (CI 70-94). IFR was associated with lower median TD (45 vs 60 Gy; p=0.008), biologically effective dose (BED) (85 vs 132; p=0.008), prescription isodose line (IDL) (68.0 vs 77.7%; p=0.007), and larger tumor size (155 vs 30.8 cc; p=0.002). Differences were maintained when comparing lesions with either IFR or MR vs. neither. IFC was better for smaller tumors, with 1-year rate of 96% (CI 73-99) for tumors <50 cc compared to 70% (CI 37-87) for ≥50 cc (p=0.005). TD of 50-60 Gy had better 1-year IFC of 96% vs 64% for 24-47.5 Gy (p<0.001). Higher IDL also had better 1-year IFC (86% for 80-85.7 vs 83% for 70-79 vs. 33% for 63.3-69.5; p=0.048). Occurrence of either IFR or MR was higher at TD 24-55 Gy vs. 60 Gy (41% vs 10%; p=0.006), with IFC/MC at 1-year of 65% vs 94% (p=0.006). Using Cox models, IFR/MR was also higher at larger tumor size (HR 11.08; p=0.001) and IDL (for 1% difference, HR 0.91; p=0.008). Estimated IFC/MC is 80% (CI 62-90) at 1 year vs 69% (CI 49-82) at 2 years. <h3>Conclusion</h3> IFC after SBRT for LM in CRC was excellent with 50 to 60 Gy. Higher BED and TD reduced IFR and MR after SBRT for liver metastases. Larger tumor size yielded a higher failure rate and may warrant additional dose. Although durable IFC is frequently achieved, there are opportunities for intensifying therapy.

Frameless Fractionated Stereotactic Radiosurgery for Meningioma and Schwannoma: An Institutional Series of 126 Cases

<h3>Purpose/Objective(s)</h3> Cobalt-60 stereotactic radiosurgery (SRS) typically employs frame-based immobilization and single-fraction treatment. In some circumstances, including close proximity to critical structures, large tumor size, and retreatment, SRS must be fractionated, with mask for immobilization. We present a large institutional experience with mask-based fractionated SRS for meningioma and schwannoma. <h3>Materials/Methods</h3> All patients treated with frameless fractionated SRS for meningioma or schwannoma between March 2017 and July 2021 at one institution were identified. Patient, tumor, and treatment variables were abstracted. The primary outcomes were one- and two-year local control (LC), which was analyzed via Kaplan-Meier analysis. This study was approved by the institution's IRB. <h3>Results</h3> One hundred and five patients with a total of 126 tumors were treated. The median follow-up time was 18.7 months. The median age at treatment was 66 years. Seventy-one percent of patients were female. Eighty-six percent of tumors (n=108) were meningioma, and the remaining 14% (n=18) were schwannoma. Of the 61 meningiomas for which pathological information was available, 33 were grade 1, 26 were grade 2, and 2 were grade 3. The most common indication for fractionation was proximity to critical structures (55.6% of tumors); other indications were retreatment (23.0%) and large size (21.4%). For the entire cohort, the mean maximal linear size was 34.6 mm; for tumors fractionated due to size, the mean size was 44.4 mm. The median total dose was 2,500 cGy (range: 1,950-3,000), and the median dose per fraction was 500 cGy (range: 500-700); the most common dose-fractionations were 2,500 cGy in 500 cGy per fraction (67.5% of patients) and 2,750 cGy in 550 cGy per fraction (17.5% of patients). The mean target volume was 8.62 cc (range: 0.13-120.0), and the mean maximum dose was 4,716 cGy (range: 3,200-6,000). The prescription isodose line was 50 to 59% for 84% of treatments (mean % IDL, 55%). Target coverage was 100% in all 126 cases. For lesions in proximity to the brainstem, mean brainstem maximum point dose (MPD) was 24.9 Gy and mean brainstem mean dose was 6.7 Gy. For lesions in proximity to the optic pathway, mean optic nerve MPD was 15.7 Gy, mean optic nerve mean dose was 6.4 Gy, mean optic chiasm MPD was 17.3 Gy, and mean optic chiasm mean dose was 7.5 Gy. One-year LC was 97.6% and two-year LC was 93.1%. Twenty-one percent of patients experienced acute grade 1-2 toxicity; there were no grade 3 or higher acute toxicities. Thirteen percent of patients had grade 1-2 radiation necrosis (RN); there were no cases of grade 3 or higher RN. <h3>Conclusion</h3> Cobalt-60 frameless fractionated SRS for benign brain tumors offers excellent local control and minimal toxicity. Frameless fractionated SRS is technically feasible, offers excellent sparing of critical structures, and is well-tolerated. Frameless fractionated SRS is an excellent treatment option for patients with large, retreated, or critically located meningioma or schwannoma.

Stereotactic Body Radiation Therapy for High-Grade Malignant Epidural Spinal Cord Compression from Solid Tumor Metastases

<h3>Purpose/Objective(s)</h3> While upfront surgical decompression is the gold standard for malignant epidural spinal cord compression (MESCC) from solid tumor metastases, not all patients are surgical candidates or undergo successful surgical Bilsky downgrading. We report oncologic and functional outcomes for patients treated with SBRT to high-grade MESCC. <h3>Materials/Methods</h3> Patients with Bilsky grade 2-3 MESCC from solid tumor metastases treated with SBRT from 2009 - 2020 were retrospectively reviewed. Patients who received upfront surgery were eligible but included only if post-surgical Bilsky grade remained ≥2. Neurologic exams, MRI imaging, pain assessments, and oral morphine equivalent (OME) opioid usage were assessed every 3-4 months in follow up. Pain response was defined as <i>complete</i> (pain level 0 on Visual Analog Scale), <i>partial</i> (pain level decrease ≥2 and at least stable OME; or stable pain level and ≥25% OME decrease), <i>stable</i> (same pain level and OME), or <i>worse</i> (higher pain level). Cumulative incidence of local recurrence (LR) was reported with death as a competing event, and overall survival (OS) was estimated with Kaplan-Meier. <h3>Results</h3> We included 143 patients with median age of 62 years (range: 14-94). The most common histologies were NSCLC (17.4%), breast (16.7%), prostate (11.1%) and sarcoma (11.1%). The majority (75.5%) of metastases were in the T-spine, 22.3% in the C-spine, and 2.1% in the L-spine. Bilsky grade 2 represented 90.9% of cases. The median prescription dose was 25 Gy (range: 12-40) in a median of 5 fractions (range: 1-5). The median prescription isodose line was 60% (range: 50-85). One-fifth (20.2%) of cases were in the re-irradiation setting. The median follow up was 8.0 mo (range: 0.4-116.9). At first post-SBRT follow-up imaging, 53.8% patients with Bilsky grade 2 were stable while 16.2% improved to grade 1. Five of 13 patients (38.4%) with Bilsky grade 3 improved to grade 1-2. Cumulative incidence of LR was 5.1%, 7.5%, and 14.1% at 6, 12 and 24 mo respectively. Of the 18 crude LRs occurring at a median of 9.7 mo (range: 0.4-43.7), the most common histologies were RCC (4), NSCLC (3), sarcoma (2) and uterine (2). Only 10.5% of patients underwent salvage surgery, at a median of 3.1 mo after SBRT (range: 0.7-35.9). Median OS was 10.7 mo, and OS was 47.2% and 32.5% at 1 yr and 2 yrs. At 3 and 6 mo after SBRT, there were 118 and 76 evaluable patients for pain/functional outcomes. Pain response in reference to pre-SBRT was complete in 45.4% and 55.7%, partial in 26.9% and 13.1%, stable in 24.1% and 27.9%, and worse in 3.7% and 3.3% of patients at 3 and 6 mo respectively. At 3 months post-SBRT, 62.7% of evaluable patients ambulated with no assistance, compared to 48.3% of the same cohort pre-SBRT. No patients developed spinal cord myelopathy. <h3>Conclusion</h3> We report the largest series to date of high-grade MESCC from solid tumor metastases treated with SBRT. Our excellent control and functional outcomes suggest SBRT is a reasonable approach in inoperable patients or cases unable to be successfully surgically downgraded.

Adjuvant Stereotactic Body Radiation Therapy (ASBRT) for Early-Stage Breast Cancer: Symptomatic Fat Necrosis is Associated with Consecutive Daily Treatments

<h3>Purpose/Objective(s)</h3> Outcomes following accelerated partial breast irradiation in select women with early-stage breast cancer are comparable to whole breast irradiation. ASBRT is an attractive treatment option, but mature toxicity outcomes are limited. Toxicity risk with SBRT has been associated with a consecutive daily schedule in other organs. In the present study, we explore the association of treatment schedule and fat necrosis. <h3>Materials/Methods</h3> Early-stage breast cancer patients (Stage 0 and I) were treated per an institutional protocol. A minimum of 4 gold fiducials were implanted around the lumpectomy cavity for target delineation and tracking. The clinical treatment volume (CTV) was defined as lumpectomy cavity with a uniform 0-10 mm expansion confined to breast tissue. The planning treatment volume (PTV), defined as the CTV with a 0-2 mm uniform expansion, was prescribed 30 Gy in 5 fractions. Breast examination and mammography were completed per routine institutional practice. A patient was deemed to have fat necrosis when breast examination identified a tumor bed mass with distinctive mammographic characteristics. <h3>Results</h3> Twenty women were treated over a 7-year period extending from September 2008 to September 2015 and followed for a minimum of 6 years. The median CTV expansion was 5 mm (range, 0-10), median PTV was 62.5 cm³ (range 15-142), median PTV/breast volume ratio was 8.3% (range 4.1-25.6), median prescription isodose line was 83% (range 75-87) and median treatment duration was 7 days (range 5-13). Seven patients were treated on 5 consecutive days (i.e., Monday through Friday). At a median follow up of 8 years (range, 6-12 years), 5 women developed fat necrosis. All 4 symptomatic patients had been treated on consecutive days and the symptomatic fat necrosis was diagnosed at a median follow-up of 5.9 years (range, 4.8-7.4). Cox regression analysis identified consecutive daily treatments as a predictor of symptomatic fat necrosis (OR: 26.8, <i>p value</i>=0.05). <h3>Conclusion</h3> Our mature findings demonstrate an association between Monday through Friday treatment and symptomatic fat necrosis. Fortunately, our research also suggests that symptomatic fat necrosis is curtailed by merely extending the treatment duration beyond 5 days. Accordingly, we believe that the Fast-Forward trial investigators should reevaluate their current assertion that 26 Gy whole breast irradiation delivered in 5 consecutive daily fractions over 5 or 7 days is a new standard treatment option. Only the yet to be completed 10-year analysis of this large prospective study will ultimately determine if delivering 5 large consecutive daily adjuvant breast radiation treatments is associated with symptomatic fat necrosis and if adding 2 additional days to the treatment course effectively curtails this adverse side-effect.

Single-fraction prostate-specific membrane antigen positron emission tomography- and multiparametric magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer local recurrences.

To analyse the efficacy and safety of focal prostate-specific membrane antigen positron emission tomography (PSMA-PET)- and multiparametric magnetic resonance imaging (mpMRI)-guided single-fraction stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer (PCa) local recurrences. Patients with PSMA-PET-positive PCa local recurrences treated with single-fraction SBRT between 2016 and 2020 were included. Identification for subsequent recurrences or metastatic spread based on increasing prostate-specific antigen (PSA) levels were evaluated using PSMA-PET imaging. A total of 64 patients were identified. Patients received various treatments before SBRT (31 patients with radical prostatectomy [RP], 18 external beam radiotherapy [EBRT] with RP, five EBRT, and the remaining 10 other combinations). The median follow-up was 21.6 months. The median PSA level before SBRT was 1.47 ng/mL. All patients received a single-fraction treatment with a median prescription dose and isodose line of 21 Gy and 65%, respectively. At the time of SBRT, six patients (9%) received an androgen deprivation therapy (ADT). PSA levels decreased after SBRT (P = 0.03) and three local recurrences were detected during the follow-up. The progression-free survival after 1-, 2-, and 3-years was 85.3%, 65.9%, and 51.2%, respectively. Six patients (9%) started ADT after SBRT due to disease progression. The rates of newly started ADT after 1-, 2-, and 3-years were 1.8%, 7.3%, and 22.7%, respectively. Grade 1 or 2 toxicities occurred in six patients (9%); no high-grade toxicity was observed. While the available data for SBRT in the PCa local recurrence setting describe outcomes for fractionated irradiations, the findings of this first analysis of single-fraction, PSMA-PET- and mpMRI-guided focal SBRT are encouraging. Such treatment appears to be a safe, efficient, and time-saving therapy even in intensively pretreated patients. Recurrence-directed treatments can delay the use of ADT and could avoid prostate bed irradiation in selected patients.

Self-Shielding Gyroscopic Radiosurgery—A First Clinical Experience, Case Series, and Dosimetric Comparison

Self-shielding gyroscopic radiosurgery (GRS) represents a technical innovation in the field of stereotactic radiosurgery. GRS does not require a radiation vault and is optimized for radiosurgical treatments. Reports on its usage are limited. We describe the first clinical experience of GRS at our institution to assess the application of GRS in the treatment of cranial tumors. Moreover, we perform a dosimetric comparison to robotic radiosurgery (RRS) with vestibular schwannoma (VS) GRS patients. Patients who were treated with GRS between July and November 2021 were included. Patient, tumor, and dosimetric characteristics were retrospectively summarized and analyzed. Forty-one patients with 48 intracranial tumors were included. Tumor entities mostly comprised VS, brain metastases, and meningiomas. The median prescription dose and isodose line were 13.5Gy and 50.0% for benign neoplasia versus 20Gy and 60.0% for malignant tumors, respectively. The mean planning target volume was 1.5 cubic centimeters. All patients received a single-fraction treatment without encountering any technical setup difficulties. Treatment plan comparisons with RRS revealed comparable plan characteristics, dose gradients, and organs at risk doses. Significant differences were detected concerning the new conformity index and number of monitor units per treatment (both P<0.01). This case series provides more evidence on the usage of self-shielding GRS in the management of cranial tumors. Dosimetric comparisons for VS cases revealed mostly equivalent dosimetric characteristics to RRS. Further clinical and physical analyses for GRS are underway.

A volume-independent conformity index for stereotactic radiosurgery.

To develop a volume-independent conformity metric called the Gaussian Weighted Conformity Index (GWCI) to evaluate stereotactic radiosurgery/radiotherapy (SRS/SRT) plans for small brain tumors. A signed bi-directional local distance (BLD) between the prescription isodose line and the target contour is determined for each point along the tumor contour (positive distance represents under-coverage). A similarity score function (SF) is derived from Gaussian function, penalizing under- and over-coverage at each point by assigning standard deviations of the Gaussian function. Each point along the dose line contour is scored with this SF. The average of the similarity scores determines the GWCI. A total of 40 targets from 18 patients who received Gamma-Knife SRS/SRT treatments were analyzed to determine appropriate penalty criteria. The resulting GWCIs for test cases already deemed clinically acceptable are presented and compared to the same cases scored with the New Conformity Index to determine the influence of tumor volumes on the two conformity indices (CIs). A total of four penalty combinations were tested based on the signed BLDs from the 40 targets. A GWCI of 0.9 is proposed as a cutoff for plan acceptability. The GWCI exhibits no target volume dependency as designed. A limitation of current CIs, volume dependency, becomes apparent when applied to SRS/SRT plans. The GWCI appears to be a more robust index, which penalizes over- and under-coverage of tumors and is not skewed by the tumor volume.

Robotic stereotactic body radiotherapy for the management of adrenal gland metastases: a bi-institutional analysis

PurposeAdrenal gland metastases (AGMs) are a common manifestation of metastatic tumor spread, especially in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). In patients with a limited systemic tumor burden, effective treatments for AGMs are needed. Due to varying fractionation schemes and limited reports, short-course treatment results for stereotactic body radiotherapy (SBRT) for AGMs are lacking. This work analyzes the outcomes of short-course SBRT for AGMs.MethodsPatients who underwent robotic SBRT for AGMs with one to five fractions were eligible for analysis.ResultsIn total, data from 55 patients with 72 AGMs from two institutions were analyzed. Most AGMs originated from renal cell carcinoma (38%) and NSCLC (35%). The median follow-up was 16.4 months. The median prescription dose and isodose line were 24 Gy and 70%, respectively. Most patients (85%) received SBRT with just one fraction. The median biologically effective dose assuming an α/β ratio of 10 (BED10) was 80.4 Gy. The local control and progression-free survival after 1 and 2 years were 92.9%, 67.8%, and 46.2%, as well as 24.3%, respectively. Thirteen patients (24%) suffered from grade 1 or 2 toxicities. The BED10 showed a significant impact on LC (p < 0.01). Treatments with a BED10 equal to or above the median were associated with a better LC (p < 0.01).ConclusionRobotic SBRT is an efficient and safe treatment modality for AGM. Treatment-associated side effects are sporadic and manageable. Results suggest short-course SBRT to be a preferable and time-saving treatment option for the management of AGMs if an adequate BED10 can be safely applied.

Utility of Intermediate Risk Volumes in Human Papilloma Associated Oropharyngeal Cancer: A Pattern of Failure Analysis

<h3>Purpose/Objective(s)</h3> Head/neck radiotherapy contouring guidelines recommend the use of an intermediate risk volume and dose around the primary target in head and neck radiotherapy. Patients with human papilloma virus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) have locoregional control (LRC) rates that are in excess of 90% with definitive radiotherapy. We hypothesized that intermediate risk volume and doses would have limited utility in these patients. <h3>Materials/Methods</h3> Following institutional review board approval, a database of p16+ and/or HPV OPSCC AJCC Stage I-III patients treated with definitive radiotherapy with or without chemotherapy was queried. Patient with documented locoregional recurrence (LRR) after the end of RT were identified. Diagnostic imaging at recurrence (rDI) was co-registered to the patient's simulation CT (sCT). The recurrence gross tumor volume (rGTV) on the rDI was contoured. In-field failure was defined as ≥95% of the recurrence volume, marginal as 20–95%, and out-of-field as ≤20% lying within the 95% high-dose prescription isodose lines. Patients with marginal or out-of-field recurrences were identified, and the initial treatment GTV was expanded by 1.3 cm to create a PTV intermediate dose (PTV-ID). The coverage of the rGTV by the PTV-ID was assessed, with potential benefit defined as near-total encompassing of the rGTV by the PTV-ID. <h3>Results</h3> A total of 534 patients with a median follow-up of 30 months were available for analysis. Actuarial LRC at 3 years was 91.2%. A total of 57 patients with LRR were identified, of which 41 had available RT treatment plans and recurrence imaging. 25 patients (61%) had in-field recurrences, 6 (14.6%) had marginal recurrences, and 10 (24.3%) had out-of-field recurrences. Of the 10 out-of-field recurrences, 4 were within elective neck volumes, 3 were in un-targeted neck regions, and 3 in areas adjacent to the primary. The combined crude marginal and out of field recurrence rate was 3%. In patients with marginal and out-of-field recurrences, none would have been ≥95% encompassed by the PTV-ID expansion. <h3>Conclusion</h3> In this large retrospective evaluation of an intermediate dose volume for patients with HPV-related OPSCC, we found no potential patients whose recurrences may have been prevented with a PTV-ID. The omission of an intermediate risk volume/dose around the primary or at-risk nodal echelons may be reasonable.

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas—A Multicenter Analysis and Review of the Literature

Simple SummaryMeningiomas represent the most common central nervous system (CNS) tumor. Despite their often benign nature, a tumor location in direct proximity to vital brain structures may lead to significant morbidity. This is the case for foramen magnum meningiomas (FMMs) as they grow at the skull base, next to the brain stem and foramen magnum. Surgical resection represents the mainstay of FMM treatments. In patients unsuitable for surgery, with tumor recurrences or tumor remnants after surgery, non-invasive treatment modalities may play a crucial role in patient management. Reports and studies on stereotactic radiosurgery (SRS) for the treatment of FMMs are scarce. This multicenter analysis reported the outcome data of 62 patients with FMMs. SRS achieved a high local tumor control and demonstrated a favorable safety profile. These results are in agreement with previous findings. SRS should be considered for selected FMM patients.Background: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. Methods: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. Results: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. Conclusions: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.

Variation in Proton Craniospinal Irradiation Practice Patterns in the United States: A Pediatric Proton Consortium Registry (PPCR) Study

Craniospinal irradiation (CSI) is commonly used for pediatric brain tumors with a propensity for spread in craniospinal fluid, principally medulloblastoma. Evolving technology has led to the use of highly conformal radiation therapy (RT) techniques for CSI, including proton therapy. Target delineation and plan coverage are critical for CSI, but there is ongoing controversy and variability in these realms, with little available data on practice patterns. We sought to characterize proton CSI practice patterns in the United States by examining CSI plans in the Pediatric Proton/Photon Consortium Registry (PPCR). PPCR was queried for data on proton CSI patients from 2015 to early 2020. Each plan was manually reviewed, determining patient position; prescription dose; and coverage of optic nerves, vertebral bodies, spinal nerve roots, sacral nerves, and cranial foramina, among other variables. Two radiation oncologists blinded to clinical data and treating institution assessed coverage at the 95% prescription isodose line and per published European Society for Paediatric Oncology guidelines. Variability in coverage was assessed with nonparametric tests and univariate and multivariate logistic regression. PPCR supplied data for 450 patients, 384 of whom had an evaluable portion of a CSI plan. Most patients (90.3%) were supine. Optic nerves were fully covered in 48.2%; sacral nerves in 87.7%; cranial foramina in 69.3%; and spinal nerves in 95.6%. Vertebral body (VB) sparing was used in 18.6% of skeletally immature cases, increasing over time (P < .001). Coverage in all categories was significantly different among treating institutions, on univariate and multivariate analyses. Cribriform plate deficits were rare, with marginal misses of the foramen ovale (17.4%) and frontal lobe (12%) most common. We found consistent variation based on treating institution in proton CSI practices including optic nerve, VB, sacral nerve, cranial, and spinal nerve coverage. These data may serve as a baseline quantification of current proton CSI practices in the United States as they continue to evolve.