Single-fraction Stereotactic Body Radiation Therapy Research Articles

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

ObjectivesMetastasis-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. MethodsSpine 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. Results522 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). ConclusionsSpine 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.

Differences between Survival Rates and Patterns of Failure of Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma Who Received Single-Fraction Stereotactic Body Radiotherapy.

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC (p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.

Long-Term Results of a Phase 1 Dose Escalation Trial of Ablative Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is increasingly used for oligometastatic disease as well as palliation, but treatment protocols for non-spine bone and nodal metastases are lacking, with a wide variety of schedules applied. Therefore, a prospective dose-escalation trial was initiated, involving 90 patients, among whom 52 (58%) had primary prostate tumors, 13 had breast tumors (14%), and 25 (28%) had other primary tumor types. All visible lymph node and/or non-spine bone oligometastases were treated in three consecutive cohorts: 5×7.0 Gy, 3×10.0 Gy, or 1×20.0 Gy. Initial results revealed no dose-limiting toxicity after a median follow-up of 17.2 months. This update provides information on long-term toxicity, local failure (LF), and progression-free survival (PFS). After a median follow-up of 50 months, no new safety signals were observed. Grade 2 toxicity was 13%, 7% and 10% in the respective cohorts (p=0.9), without grade 3-5 toxicities. LF rates were 9%, 3%, and 6% (P=.5) for the respective treatment groups, with an overall cumulative risk of LF of 7% (95% CI 2-12) at 4 years. Median PFS was 16.5 months (95% CI 9.8-21.5), and 4-year PFS was 21% (95% CI 14-32). Median overall survival across groups was not reached (95% CI 52.8 – not reached), 4-year OS was 68% (95% CI 59-78). A subset of patients (23%) remained long-term disease-free, 37% had oligoprogressive disease at first recurrence and 40% developed polymetastatic relapse. In conclusion, the safe and effective use of dose-escalated single-fraction SBRT for bone and lymph node metastases is supported by this trial, especially considering patient-convenience and cost-effectiveness. Caution is needed when generalizing these outcomes beyond breast and prostate cancer, given their underrepresentation in our study.

Long-Term Survival and Failure Outcomes of Single-Fraction Stereotactic Body Radiation Therapy in Early Stage NSCLC

IntroductionThis study aims to report our 13-year institutional experience with single-fraction stereotactic body radiation therapy (SF-SBRT) for early stage NSCLC. MethodsA single-institutional retrospective review of patients with biopsy-proven peripheral cT1-2N0M0 NSCLC undergoing definitive SF-SBRT between September 2008 and May 2022 was performed. All patients were treated to 27 Gy with heterogeneity corrections or 30 Gy without. Primary outcomes were overall survival and progression-free survival. Secondary outcomes included local failure, nodal failure, distant failure, and second primary lung cancer. ResultsAmong 263 eligible patients, the median age was 76 years (interquartile range [IQR]: 70–81 y) and median follow-up time was 27.2 months (IQR: 14.25–44.9 mo). Median tumor size was 1.9 cm (IQR: 1.4–2.6 cm), and 224 (85%) tumors were T1. There were 92 patients (35%) alive at the time of analysis with a median follow-up of 34.0 months (IQR: 16.6–50.0 mo). Two- and five-year overall survival was 65% and 26%, respectively. A total of 74 patients (28%) developed disease progression. Rates of five-year local failure, nodal failure, distant failure, and second primary lung cancer were 12.7%, 14.7%, 23.5%, and 12.0%, respectively. ConclusionsConsistent with multiple prospective randomized trials, in a large real-world retrospective cohort, SF-SBRT for peripheral early stage NSCLC was an effective treatment approach.

Long-term outcomes of single and five fraction schedules of stereotactic body radiation therapy for early-stage central or peripheral NSCLC: Neither fractionation nor location matter?

8538 Background: Due to concerns with toxicity, treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) often involves different fractionation schemes for peripheral and centrally located tumors. There is a paucity of long-term SBRT survival outcomes comparing peripheral versus central NSCLC. Methods: This is a single-institution observational cohort study of patients diagnosed with early-stage NSCLC (T1-2N0M0) who underwent 27 Gy in 1 fraction or 50 Gy in 5 fractions with heterogeneity correction at Roswell Park Comprehensive Cancer Center between September 2008 to December 2018. All patients treated with single-fraction SBRT had peripheral NSCLC and those treated with five-fraction SBRT had central NSCLC. Clinically relevant variables including age, gender, race, Karnofsky Performance Status (KPS), histology (adenocarcinoma, squamous cell carcinoma, NSCLC not otherwise specified), T stage, smoking status, tumor location, and the year of SBRT delivery were obtained retrospectively. Cox multivariable analysis (MVA), Kaplan-Meier plot, and log-rank test were performed to evaluate progression-free survival (PFS) and overall survival (OS). Fine-Gray competing risk MVA was performed to evaluate local failure (LF), nodal failure (NF), and distant failure (DF) with death as a competing event. To reduce selection bias, propensity score matching was performed between single- versus five-fraction SBRT cohorts. Results: A total of 265 patients (142 female [53.6%]; median age 77 years) met our criteria. There were 74 (27.9%) and 191 (72.1%) patients with central tumors treated with five-fraction SBRT and peripheral tumors treated with single-fraction SBRT, respectively. On Cox MVA, there was no statistically significant difference in OS (peripheral vs central tumors: adjusted hazards ratio [aHR] 1.04, 95% confidence interval [CI] 0.74-1.46, p=0.81) and PFS (peripheral vs central tumors: aHR 1.05, 95% CI 0.76-1.45, p=0.77). On Fine-Gray competing risk MVA comparing peripheral vs. central tumors, there was no statistically significant difference in LF, NF, and DF. After propensity score matching, 68 matched pairs were identified for peripheral vs. central tumors with similar results. Conclusions: Among patients with early-stage NSCLC treated with SBRT central versus peripheral location was associated with similar long-term survival and tumor recurrence outcomes.

Stereotactic body radiation therapy (SBRT) for spinal metastases: 12years of a single center experience.

To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. Patients with spine metastases treated with SBRT (1 fraction/18Gy or 5 fractions/7Gy) during the last 12years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18Gy (75%) or 5 fractions/7Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer

The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC. Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire. Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment. For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted.

Comparison of Survival Outcomes of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Early-Stage Central or Peripheral NSCLC

The treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) frequently involves different fractionation schemes for peripheral and central tumors due to concerns with toxicity. We performed an observational cohort study to determine survival outcomes for patients with peripheral and central NSCLC treated with SBRT. A single-institutional database of patients with early-stage NSCLC treated with SBRT from September 2008 to December 2018 was evaluated. Outcomes were progression-free survival (PFS), overall survival (OS), local failure (LF), nodal failure (NF), and distant failure (DF). Cox multivariable analysis (MVA), Kaplan-Meier plotting, Fine-Gray competing risk MVA, and propensity score matching were performed. A total of 265 patients were included with a median follow-up of 44.2 months. There were 191 (72%) and 74 (28%) patients with peripheral and central tumors treated with single-fraction SBRT to a dose of 27 Gy and five-fraction SBRT to a dose of 50 Gy, respectively. On Cox MVA, there was no difference in OS (adjusted hazards ratio (aHR) of 1.04, 95% CI of 0.74-1.46) or PFS (aHR of 1.05, 95% CI of 0.76-1.45). On Fine-Gray competing risk MVA, there were no differences in LF, NF, or DF. Propensity matching confirmed these findings. The survival outcomes of patients treated with SBRT for early-stage NSCLC were equivalent for central and peripheral tumors.

Assessing the impact of intrafraction motion correction on PTV margins and target and OAR dosimetry for single-fraction free-breathing lung stereotactic body radiation therapy.

The objective of this research is to investigate intrafraction motion correction on planning target volume (PTV) margin requirements and target and organ-at-risk (OAR) dosimetry in single-fraction lung stereotactic body radiation therapy (SBRT). Sixteen patients (15 with upper lobe lesions, 1 with a middle lobe lesion) were treated with single-fraction lung SBRT. Cone-beam computed tomography (CBCT) images were acquired before the treatment, between the arcs, and after the delivery of the treatment fraction. Shifts from the reference images were recorded in anterior-posterior (AP), superior-inferior (SI), and lateral (LAT) dimensions. The deviations from the reference image were calculated for 3 clinical scenarios: not applying intratreatment couch shifts and not correcting for pretreatment deviations < 3 mm ( scenario 1), not applying intratreatment couch shifts and correcting for pretreatment deviations < 3 mm ( scenario 2), and applying all pre- and intratreatment couch shifts (scenario 3). PTV margins were determined using the van Herk formalism for each scenario and maximum and average deviations were assessed. The clinical scenarios were modelled in the treatment planning system based on each patient dataset to assess target and OAR dosimetry. Calculated lower-bound PTV margins in the AP, SI, and LAT dimensions were [4.6, 3.5, 2.3] mm in scenario 1, [4.6, 2.4, 2.2] mm in scenario 2, and [1.7, 1.2, 1.0] mm in scenario 3. The margins are lower bounds because they do not include contributions from nonmotion related errors. Average and maximum intrafraction deviations were larger in the AP dimension compared to the SI and LAT dimensions for all scenarios. A unidimensional movement (several mm) in the negative AP dimension was observed in clinical scenarios 1 and 2 but not scenario 3. Average intrafraction deviation vectors were 1.2, 1.1, and 0.3 mm for scenarios 1, 2, and 3, respectively. Modelled clinical scenarios revealed that using scenario 3 yields significantly fewer treatment plan objective failures compared to scenarios 1 and 2 using a Wilcoxon signed-rank test. Intratreatment motion correction between each arc may enable reductions PTV margin requirements. It may also compensate for unidimensional negative AP movement, and improve target and OAR dosimetry.

Brachial Plexopathy After Single-Fraction Stereotactic Body Radiation Therapy in Apical Lung Tumors

The objective of this study was to evaluate the incidence of brachial plexus injury (BPI) after single-fraction stereotactic body radiation therapy (SBRT) to apical lung tumors. A retrospective cohort analysis was performed of all patients treated with single-fraction lung SBRT at our institution from 2007 to 2022. Apical tumors were identified as those with an epicenter located above the arch of the aorta. Dosimetric analysis of dose to the brachial plexus (BP) was done using both the subclavian vessel (SCV) surrogate structure and anatomic BP. BPI was assessed per Common Terminology Criteria for Adverse Events, version 4.0, as regional paresthesia, marked discomfort and muscle weakness, and limited movement of the arm or hand. A total of 45 patients met inclusion criteria with median follow-up of 21 months. There were 9 patients who exceeded the BP dose constraint using the SCV or anatomic BP volume. Only 1 patient (2.2%) developed grade 2 BPI, occurring 7 months after SBRT. Dose to the anatomic BP for the affected patient was 26.39 Gy. For the entire cohort, the median SCV and anatomic maximum BP doses were 8.44 and 7.14 Gy, respectively. There is considerable variability in dose delivered to the BP after SBRT to apical lung tumors. BPI after single-fraction SBRT to apical tumors is rare and rates are comparable with those reported with multifraction regimens.

Prospective Evaluation of Stereotactic Body Radiation Therapy (SBRT) for Patients with Metastatic Epidural Spinal Cord Compression

<h3>Purpose/Objective(s)</h3> Metastatic epidural spinal cord compression (MESCC) can be very painful and disabling. We hypothesized that an initial fraction of SBRT would provide rapid decompression and allow for potential dose escalation via a follow up treatment. Our primary objective was to assess the feasibility of a staged SBRT approach to provide short-interval treatment response. Secondary endpoints included pain control and quality of life (QoL). <h3>Materials/Methods</h3> This single institution, prospective study enrolled non-surgical candidates with MESCC from 07/2015 to 02/2018. Those with spine instability (SINS>12), bony retropulsion, or radiosensitive histologies were excluded. After baseline imaging (MRIpre), patients received SBRT (10-16 Gy) and a short interval MRI within 2-3 weeks (MRI1). Subsequently, patients could receive an additional treatment at the discretion of the treating physician. A second MRI was completed 8-10 weeks post-tx (MRI2). QoL questionnaires and pain scores were obtained at all time points. The primary endpoint was the smallest cord-disease distance (CDD) in the axial plane and the thecal sac patency (TSP), defined as the thecal sac area at the level of maximal compression divided by the average thecal sac area one level above and below. Secondary endpoints included pain scores and QoL using the Functional Assessment of Cancer Therapy – General (FACT-G). Statistical comparisons utilized the Wilcoxson signed-rank test. <h3>Results</h3> 22 patients were enrolled in the study and received SBRT. The most common primary diagnoses were lung (36%) and prostate (32%) cancer. The most common initial SBRT doses were 16 Gy (41%) and 14 Gy (36%). 12 patients completed all 3 scans and 3 other patients completed 2 scans (MRIpre and either MRI1 or MRI2). No patient received a second,adaptive fraction of radiation (due to lost to follow up, systemic progression, or no local progression). TSP significantly increased on MRI1 (median change 9%, IQR 1%-28%, p = 0.034) and on MRI2 (median change 24%, IQR 12-32%, p = 0.002). CDD did not increase significantly on MR1 (median change 0.0 mm, IQR 0-0.3 mm, p = 0.125) but did on MRI2 (median change 1.5 mm, IQR 0-1.8 mm, p = 0.001). On radiology report, 23% had disease improvement on MRI1, all of whom received 16 Gy. 64% had disease improvement on MRI2. No patients progressed neurologically. There was a numerical decrease in best and worst pain score over time (p=0.093). FACT-G scores did not change significantly over time. There were no grade 3 or greater toxicities related to RT. <h3>Conclusion</h3> Single-fraction SBRT can provide rapid decompression of epidural disease safely and quickly. Radiosurgical decompression can be a feasible alternative to surgery in patients with MESCC, especially as a large segment of such patients are non-surgical candidates. A follow up study comparing SBRT to 3D CRT is being planned.

Systematic Review of Single-Fraction Stereotactic Body Radiation Therapy for Early Stage Non-Small-Cell Lung Cancer and Lung Oligometastases: How to Stop Worrying and Love One and Done.

Simple SummaryAdoption of single-fraction stereotactic body radiation therapy for lung tumors has been limited among different institutions even during the coronavirus disease 2019 (COVID-19) pandemic. Potential reasons may include a lack of familiarity and concerns regarding potential toxicities. To address this knowledge gap, we performed a systematic review of prospective literature on single-fraction SBRT. Our PubMed search of prospective trials resulted in nine studies that showed favorable local control and survival outcomes among peripheral tumors. Many toxicities were grade 1–2, with 0–17% of patients experiencing grade ≥3 toxicity. Encouraging outcomes suggest that the utility of single-fraction stereotactic body radiation therapy may extend beyond the current COVID-19 pandemic.Adoption of single-fraction lung stereotactic body radiation therapy (SBRT) for patients with medically inoperable early stage non-small-cell lung cancer (NSCLC) or oligometastatic lung disease, even during the coronavirus disease 2019 (COVID-19) pandemic, was limited despite encouraging phase II trial results. Barriers to using single-fraction SBRT may include lack of familiarity with the regimen and lack of clarity about the expected toxicity. To address these concerns, we performed a systematic review of prospective literature on single-fraction SBRT for definitive treatment of early stage and oligometastatic lung cancer. A PubMed search of prospective studies in English on single-fraction lung SBRT was conducted. A systematic review was performed of the studies that reported clinical outcomes of single-fraction SBRT in the treatment of early stage non-small-cell lung cancer and lung oligometastases. The current prospective literature including nine trials supports the use of single-fraction SBRT in the definitive treatment of early stage peripheral NSCLC and lung oligometastases. Most studies cite local control rates of >90%, mild toxicity profiles, and favorable survival outcomes. Most toxicities reported were grade 1–2, with grade ≥3 toxicity in 0–17% of patients. Prospective trial results suggest potential consideration of utilizing single-fraction SBRT beyond the COVID-19 pandemic.

Patterns of Care in Stereotactic Body Radiation Therapy Fractionation Schedules in Non-Small Cell Lung Cancer in the United States From 2004-2016

Stereotactic Body Radiation Therapy (SBRT) is considered standard of care for inoperable early stage non-small cell lung cancer (NSCLC) and is commonly delivered in 1-5 fractions. Single fraction SBRT is supported by randomized data demonstrating equivalent safety compared to fractionated approaches. The purpose of this study is to measure trends in the utilization of SBRT fractionation in NSCLC patients in the National Cancer Database (NCDB) from 2004-2016.The NCDB was queried for patients with cT1-T3N0M0 NSCLC who were treated with a known SBRT dosing schema during the study period (including 30-34 Gy/1 fraction, 54-60 Gy/3 fractions, 48-50 Gy/4 fractions, and 50-60 Gy/5 fractions). Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received SBRT using 1, 3, 4, and 5 fractions. Average annual percentage changes (AAPC) were computed and compared to determine if a significant change (defined a priori as P < 0.01) occurred in the use of different fractionation schemes over time. Multivariable analysis was used to evaluate factors associated with receipt of single fraction SBRT.The analytic cohort consisted of 39,536 patients. Use of 3 fraction SBRT decreased from 72.6% in 2004 to 20.3% in 2016 (AAPC -10.6% per year, 95% CI: [-12.1%, -9.1%], P < 0.001). During this interval, a corresponding increase in the use of 5 fraction SBRT also occurred, from 6.5% in 2004 to 53.7% in 2016 (AAPC +18.3% per year, 95% CI: [+13.3%, +23.4%], P < 0.001). No significant change was observed in single fraction and 4 fraction SBRT utilization; < 1% of patients per year received single fraction SBRT in all but three years of the study with a 1.1% percent utilization rate in 2016. On logistic regression, cT2 patients were less likely to receive single fraction SBRT (Odds Ratio 0.592, 95% CI: 0.414-0.846) while academic facility (Odds Ratio 5.821, 95% CI: 4.331-7.823) and Charlson Deyo Score > 2 (Odds Ratio 1.447, 95% CI: 1.038-2.017) were significantly associated with receipt of single fraction SBRT. Age, insurance, distance to treatment facility, and treatment year were not significantly associated with single fraction SBRT.Single fraction SBRT use remained scarce in the United States during 2004-2016, with no clear indication of increased utilization after 2014 when RTOG0915 was first reported. With prospective evidence that long-term toxicity, local control, and survival are similar to 3-4 fraction regimens, the application of single fraction SBRT in the clinic may warrant further interest in light of the recent COVID-19 pandemic and the implementation of the alternative payment model.

Clinical and dosimetric risk factors for vertebral compression fracture after single-fraction stereotactic body radiation therapy for spine metastases

ObjectivesThis analysis was performed to evaluate the incidence of vertebral compression fracture (VCF) and determine the contributing factors for VCF in patients undergoing single-fraction stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM). MethodsA retrospective review of medical records was conducted for patients undergoing SBRT for SBM at our institution between January 2010 and December 2018. Patients who had undergone neither pre-SBRT surgical excision nor post-SBRT prophylactic fixation were included. The effects of clinical and dosimetric parameters were analyzed with respect to VCF risk. The following dosimietric parameters of the planning target volume (PTV) were calculated: mean/minimum/maximum dose, radiation dose to 10–90% volume, and irradiated volume receiving more than 10–25 Gy (PTV_V10 – 25 Gy). ResultsAmong 163 patients (179 vertebrae), 21 (12.8%) experienced VCF. The 1-year and 2-year VCF rates were 12.1% and 13.2%, respectively. Among dosimetric parameters, PTV_V15 Gy was the most significant for VCF prediction. In a univariate analysis, breast or prostate primary, no vertebral body collapse, and PTV_V15 Gy ≤42 cm3 were significantly associated with a lower incidence rate of VCF. In a multivariate analysis, PTV_V15 Gy was the only significant factor for VCF risk. The 1-year VCF rate was 3.8% in patients with PTV_V15 Gy ≤42 cm3, while it was 22.1% in those with PTV_V15 Gy > 42 cm3 (p < 0.01). ConclusionsSBRT-related VCF was found in 12% of patients in our institution. The PTV_V15 Gy is a significant factor for VCF prediction.

Simulated Single Fraction Stereotactic Body Radiation Therapy for the Treatment of Abdominal Oligometastatic Disease with Online Adaptive Magnetic Resonance Guidance: A Feasibility Study

Local ablative therapy improves overall survival in patients with limited oligometastatic disease. Single fraction SBRT is efficient and is safe in several body sites and can provide a high rate of local control, with 20Gy in 1 fraction commonly used in Europe. However, treating metastases in the abdomen is difficult due close proximity to mobile luminal organs and poor visualization on cone beam CT. The purpose of this study is to determine the feasibility of delivering MR-guided adaptive stereotactic body radiation therapy (SBRT) in a single fraction for abdominal metastases. Patients with abdominal metastases within 8mm from luminal organs treated with hypofractionation or SBRT using maximum inhale breath hold (MIBH) respiratory gating on an integrated MR-Linac or MR-cobalt radiotherapy system were retrospectively analyzed. Single fraction SBRT plans were created on the original MRI simulation with dose constraints from the AAPM Task Group 101 and Timmerman et al. Optimized PTVs (PTVopt) created by a Boolean subtraction of the 3-5mm expansion around luminal organs from the 3mm expansion around the GTV. Using a prescription of 24Gy in 1 fraction, goals included PTV V95% > 90%, PTVopt V95% > 90%, and PTVopt D99% > 20Gy with no OAR dose violations. The single fraction plans were tested on 5 fractional MRI scans. Dosimetric data was collected with the original plan (“predicted”) and after the plan was adapted using an isotoxic approach to the daily re-contoured luminal organ anatomy (“Re-optimized”). The Wilcoxon rank sum test was used to compare dosimetric data and the frequency of meeting dosimetric goals between the multi-fraction and single fraction baseline plans and between the predicted and re-optimized fractional plans. Ten patients with abdominal metastases (4 liver, 3 lymph node, 2 kidney, and 1 adrenal site) with GTV mean and range of 25.5 (1.64, 84.2) mL of various histologies were analyzed. The multi-fraction and single fraction plans mean PTV V95% and PTVopt V95% were 89.7% vs. 81.5% and 97.0% vs. 90.9% respectively (all p>0.05), while 2/10 of both the multi-fraction and single fraction plans had a PTVopt V95% < 90%, and no OAR dose constraints were violated. Comparing the predicted and re-optimized fractional plans, there was a statistically significant, 32.8% increase in the mean PTVopt D99% and 68% decrease in the mean frequency of OAR dose violations (Table 1). Single fraction SBRT for the treatment of abdominal metastases with online adaptive MR guidance is feasible and may be an efficient alternative to multi-fraction treatments. Online MR-guided adaptation is required to maintain adequate target coverage while respecting OAR dose constraints.Abstract 2406; TableTable 1: Isotoxic OptimizationMeanFrequencyPTV V95% (%)PTVopt V95% (%)PTVopt D99% (Gy)PTV V95% > 90%PTVopt V95% > 90%PTVopt D99% > 20GyOAR ViolationsPredicted81.187.917.40.240.680.240.68Re-optimized84.892.822.60.420.820.740p-value0.680.310.01*0.160.360.01*0.001* Open table in a new tab

Safety, Efficacy, and Patterns of Failure After Single-Fraction Stereotactic Body Radiation Therapy (SBRT) for Oligometastases

PurposeFewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease.Methods and MaterialsBetween February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST).ResultsIn total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively.ConclusionsSF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.

A Pilot Trial Evaluating Stereotactic Body Radiation Therapy to Induce Hyperemia in Combination With Transarterial Chemoembolization for Hepatocellular Carcinoma

Despite the survival benefit of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), a majority of tumors recur, attributed to hypovascularity and treatment resistance. Preclinical studies show that moderate radiation doses induce changes in tumor permeability and perfusion, suggesting an opportunity for TACE sensitization by radiation. In this prospective phase 1 trial, we evaluated the feasibility, safety, tolerability, response, and functional magnetic resonance imaging (MRI) changes associated with single-fraction stereotactic body radiation therapy (SBRT) followed by TACE within 24 hours. Patients with HCC, 1 to 3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hours. Secondary endpoints included safety, tolerability, perfusional changes via functional MRI, overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression, progression-free survival, and overall survival. Sixteen patients were enrolled, and 13 received SBRT and TACE. Median follow-up was 15.3 months. Best overall ORR and CBR were 76.9% and 92.3%, respectively. The 1- and 3-month ORR was 76.9% and 69.2%, respectively, and 1- and 3-month CBR was 92.3% and 69.2%, respectively. Median overall survival, progression-free survival, and freedom from local progression were 14.0, 5.2, and 5.9 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity were 85% and 38%, respectively. No grade 3 to 4 toxicities were recorded. One grade 5 toxicity occurred due to hemorrhage 4 days after TACE. On dynamic contrast-enhanced MRI, the transfer rate constant from blood plasma to extracellular extravascular space (kpe) increased within 6 hours post-SBRT but decreased by 24 hours. We hypothesized a strategy of SBRT preceding TACE for the purpose of enhancing TACE delivery and efficacy and tested this strategy in a small pilot study. We found that single-dose SBRT followed by TACE within 24 hours is feasible and tolerable. Dynamic contrast-enhanced MRI revealed acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination and the effects of SBRT on the HCC microenvironment.

Single-Fraction Radiotherapy (SFRT) For Bone Metastases: Patient Selection And Perspectives.

Bone metastases are a frequent and important source of morbidity in cancer patients. Stereotactic body radiation therapy (SBRT) is an established treatment option for local control and pain relief of bone metastases, and it is increasingly used as upfront treatment, postoperative consolidation or salvage treatment after prior RT. However, heterogeneity of dose schedules described in literature represents a severe limitation in the definition of the role of SBRT as a standard of care. No consensus is available on the use of single versus multiple fraction SBRT for bone metastases. Advantages of single-fraction SBRT include shorter overall duration of treatment, absence of inter-fraction uncertainty, improved compliance, theoretical increased efficacy, and lower costs. However, caution has been advised due to reports of severe late toxicities, in particular, vertebral collapse fracture (VCF). The aim of this paper is to review dose fractionation and indications for the management of bone metastases using SBRT.

A Phase I Trial Evaluating Stereotactic Body Radiation Therapy to Induce Hyperemia in Combination with Transarterial Chemoembolization for Hepatocellular Carcinoma

Transarterial chemoembolization (TACE) is indicated in patients with intermediate-stage, unresectable hepatocellular carcinoma (HCC). Stereotactic body radiation therapy (SBRT) is increasingly being used in HCC. Preclinical studies show that moderate radiation doses (5-10 Gy) induce acute changes in tumor permeability and perfusion. Thus, we hypothesize that SBRT followed by TACE within 24 hours promotes sensitization to TACE. In this prospective phase I trial, we evaluated the feasibility, safety, tolerability, and functional magnetic resonance imaging (MRI) changes associated with single-fraction SBRT followed by TACE within 24 hrs. Patients with HCC, 1-3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hrs. Secondary endpoints included safety, tolerability, tumor perfusion changes via dynamic-contrast enhanced (DCE) MRI (at 6 or 24 hrs after SBRT), overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS). Tumor response and progression were graded using modified RECIST criteria. The uni-directional exchange rate constants kep (interstitial space to blood plasma) and kpe (blood plasma to interstitial space) were reported as measures of vascular permeability/perfusion. A total of 16 patients were enrolled, and all but one patient received SBRT. Within 24 hours, 13 of these 15 patients successfully underwent TACE. The median age was 64 years (range 48 to 79) and 84.6% of patients were males. Median tumor size was 5.6 cm (range 2.0 to 12.0). Median follow up for living patients is 12.6 months. Crude ORR and CBR are 58% and 75%, respectively. Median OS, PFS, and FFLP are 14.2 months, 6 months, and 5.3 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity are 85% and 38%, respectively. There were no grade 3 or 4 toxicities. One patient died due to TACE-related hemorrhage 4 days after TACE (grade 5). Regarding DCE-MRI metrics, kpe showed a rapid increase within 6 hrs post-SBRT (mean +300.0%, range -6% to +1030%, p=0.01), but a decrease by 24 hrs (mean -34%, range -75% to +17%, p=0.05). A similar trend was also observed for kep, with an increase within 6 hrs post-SBRT (mean +61.3%, range -50% to +218%, p=0.07) and return to near baseline by 24 hrs (mean +21%, range -29% to +155%, p=0.23). Single-fraction SBRT followed by TACE within 24 hrs is a feasible and tolerable strategy for intermediate-stage HCC. DCE-MRI analysis revealed significant acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination, and the effects of SBRT on the HCC microenvironment.

Stereotactic Body Radiation Therapy Boost for Intermediate-Risk Prostate Cancer: A Phase 1 Dose-Escalation Study

High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost. Patients had intermediate-risk PCa and were accrued to 3 different SBRT single-fraction dose-level cohorts (10Gy, 12.5Gy, and 15Gy). All received supplemental radiation therapy afterwards (37.5Gy in 15 fractions). Three gold fiducials were implanted for image guidance. Patients were simulated and treated with a foley catheter and intrarectal balloon. A T2 magnetic resonance imaging scan was used for contouring, and a cine magnetic resonance imaging scan was used tocalculate patient-specific internal target volume margins. Toxicity and quality-of-life data were collected using Common Terminology Criteria for Adverse Events v3.0 and the Expanded Prostate Cancer Index Composite. 30 patients were accrued, 10 in each cohort. Median follow-up was 72months. 60% had unfavorable intermediate-risk PCa. Two patients in the 15Gy cohort developed late grade ≥3 gastrointestinal and genitourinary toxicity, with 1 patient suffering from a grade-4 rectal fistula after a rectal ulcer was biopsied repeatedly. Two patients had biochemical failure. Median PSA nadir was 0.4ng/mL with 10Gy, 0.09ng/mL with 12.5Gy and 0.07ng/mL with 15Gy. Median PSA at 4years as well as proportion achieving a nadir <0.2ng/mL improved significantly with higher doses. There was no significant change in quality of life from baseline in any of the domains, and the minimal clinically important change was not statistically different between the 3 cohorts. Other than a grade 4 toxicity, which may in part be due to repeated biopsies of a rectal ulcer, single-fraction SBRT boost was feasible and well tolerated. Larger studies are warranted to better document the outcomes of such an approach.