Definitive Stereotactic Body Radiation Therapy Research Articles

An in-silico planning study of stereotactic body radiation therapy for polymetastatic patients with more than ten extra-cranial lesions

Background and purposeLimited data is available about the feasibility of stereotactic body radiation therapy (SBRT) for treating more than five extra-cranial metastases, and almost no data for treating more than ten. The aim of this study was to investigate the feasibility of SBRT in this polymetatstatic setting. Materials and methodsConsecutive metastatic melanoma patients with more than ten extra-cranial metastases and a maximum lesion diameter below 11 cm were selected from a single-center prospective registry for this in-silico planning study. For each patient, SBRT plans were generated to treat all metastases with a prescribed dose of 5x7Gy, and dose-limiting organs (OARs) were analyzed. A cell-kill based inverse planning approach was used to automatically determine the maximum deliverable dose to each lesion individually, while respecting all OARs constraints. ResultsA total of 23 polymetastatic patients with a medium of 17 metastases (range, 11–51) per patient were selected. SBRT plans with sufficient target coverage and respected OARs dose constraints were achieved in 16 out of 23 patients. In the remaining seven patients, the lungs V5Gy < 80 % and the liver D700 cm3 < 15Gy were most frequently the dose-limiting constraints. The cell-kill based planning approach allowed optimizing the dose administration depending on metastases total volume and location. ConclusionThis retrospective planning study shows the feasibility of definitive SBRT for 70% of polymetastatic patients with more than ten extra-cranial lesions and proposes the cell-killing planning approach as an approach to individualize treatment planning in polymetastatic patients’.

Exploring published and novel pre-treatment CT and PET radiomics to stratify risk of progression among early-stage non-small cell lung cancer patients treated with stereotactic radiation

PurposeDisease progression after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) occurs in 20–40% of patients. Here, we explored published and novel pre-treatment CT and PET radiomics features to identify patients at risk of progression. Materials/MethodsPublished CT and PET features were identified and explored along with 15 other CT and PET features in 408 consecutively treated early-stage NSCLC patients having CT and PET < 3 months pre-SBRT (training/set-aside validation subsets: n = 286/122). Features were associated with progression-free survival (PFS) using bootstrapped Cox regression (Bonferroni-corrected univariate predictor: p ≤ 0.002) and only non-strongly correlated predictors were retained (|Rs|<0.70) in forward-stepwise multivariate analysis. ResultsTumor diameter and SUVmax were the two most frequently reported features associated with progression/survival (in 6/20 and 10/20 identified studies). These two features and 12 of the 15 additional features (CT: 6; PET: 6) were candidate PFS predictors. A re-fitted model including diameter and SUVmax presented with the best performance (c-index: 0.78; log-rank p-value < 0.0001). A model built with the two best additional features (CTspiculation1 and SUVentropy) had a c-index of 0.75 (log-rank p-value < 0.0001). ConclusionsA re-fitted pre-treatment model using the two most frequently published features – tumor diameter and SUVmax – successfully stratified early-stage NSCLC patients by PFS after receiving SBRT.

The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand?

Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor whilst sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for the traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as an alternative to brachytherapy boost after external beam RT. It is also used as a primary treatment option for elderly or medically unfit patients. More recently, an SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications.

Sinoatrial Node Dose Is Associated With Worse Survival in Patients Undergoing Definitive Stereotactic Body Radiation Therapy for Central Lung Cancers

Our purpose was to evaluate the clinical consequences of sinoatrial node (SAN) and atrioventricular node (AVN) irradiation in patients undergoing stereotactic body radiation therapy (SBRT) for central non-small cell lung cancer (NSCLC) tumors. A single-institutional retrospective review of patients with primary NSCLC undergoing definitive SBRT for centrally located thoracic tumors from February 2007 to December 2021 was performed. The SAN and AVN were contoured in accordance with a published contouring atlas, and the maximum dose (Dmax) and mean dose (Dmean) for each structure were calculated. Sequential log rank testing between the 50th and 90th percentiles was used to identify potential cutoff values for the corresponding dosimetric parameters and overall survival. Among 93 eligible patients, the median age was 72.5 years (IQR, 66.6-78.3), and median follow-up was 32.4 months (IQR, 13.0-49.6). The median SAN Dmax and Dmean were 95 cGy (range, 9-5394) and 58 cGy (range, 7-3168), respectively. The median AVN Dmax and Dmean were 45 cGy (range, 4-2121) and 34 cGy (range, 3-1667), respectively. Candidate cutoff values for SAN Dmax and Dmean were 1309 and 836 cGy, respectively. No associations between AVN parameters and survival outcomes were identified. Upon multivariate Cox regression, the SAN Dmax cutoff (hazard ratio [HR], 2.03 [1.09-3.79]; P=.026) and SAN Dmean cutoff (HR, 2.22 [1.20-4.12]; P=.011) were significantly associated with overall survival. For noncancer-associated survival, the SAN Dmax cutoff trended toward significance (HR, 2.02 [0.89-4.57]; P=.092), and the SAN Dmean cutoff remained significantly associated (HR, 2.34 [1.05-5.18]; P=.037). For patients undergoing SBRT for NSCLC, SAN Dmax and Dmean were significantly associated with worse overall survival using cut-off values of 1309 and 836 cGy, respectively. Further studies examining the effect of SAN irradiation during SBRT are warranted.

Utility of Stereotactic Body Radiation Therapy in Establishing Local Control for Patients With Invasive Breast Cancer Not Undergoing Definitive Surgery

Surgery is the backbone of breast cancer (BC) treatment. For patients who cannot undergo surgery, improving local control (LC) of the primary tumor is paramount. To that end, this study explored the role of stereotactic body radiation therapy (SBRT). Between 2015 and 2022, 21 nonsurgical candidates (10 metastatic, 11 stage IA-IIIC) received 23 SBRT courses to primary BC. Seven were analyzed retrospectively; 15 are currently enrolled in a prospective study. SBRT (40 Gy/5 fractions) was delivered every other day. Follow-up imaging was reviewed. Acute (≤3 months) and late toxicities were evaluated using Common Terminology Criteria for Adverse Events, version 5. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Median age was 78.4 years (45.9-97.3). Median follow-up was 14.7 months (3.3-70.3). Median pre-SBRT index lesion size was 3.1 cm (0.5-14.5) and planning treatment volume was 32.4 cc (11.5-522.4). Initial posttreatment imaging performed at a median 4.0 months (0.6-11.9) post-SBRT demonstrated median decrease in index lesion size of 20.8% (0%-100%); SUV reduction of 65.2% (20.8%-100%). Second follow-up scans at a median 7.8 months post-SBRT showed 62% (0%-100%) and 88% (33.3%-100%) median reduction in tumor size and SUV, respectively, compared with pre-SBRT values. The estimated LC rate was 100% at 6 months and 93.3% at 12, 24, and 36 months. Local progression occurred in 1 case 9.5 months after SBRT, after an initial response. Regional progression occurred in 4 cases (17.4%) at a median 18.6 months (5.2-22.7) post-SBRT. Six patients (35.3%) developed distant progression at a median 2.7 months (0.9-16.2). The estimated OS was 85.7% at 6 months, 69.6% at 12 months, and 63.8% at 24 and 36 months. The rates of acute toxicity were G1: 47.8%, G2: 4.3%, G3: 8.7%, and G4: 0%. Definitive SBRT for primary BC resulted in good LC in nonsurgical patients and was well-tolerated. Considering the pattern of progression, additional approaches to improve regional/distant control should be investigated.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old-Updated Results.

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports updated outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. Between April 2006 and December 2022, 6,130 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator. Information was available for 4,143 patients. 3568 (86.12%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 575 (13.88%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 1,035 (24.98%) of these cases. The mean age was 67.4 years old. 48 patients were younger than 50 years old (mean age 46.6). 4,095 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 43.75%, 50.00%, 6.25% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 23.88%, 57.05%, 19.07% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 47.92%, 7 in 47.92%, and 8-10 in 4.16%. 44 younger patients were treated with SBRT alone. 4 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.42%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 29.84%, 7 in 54.14%, and 8-10 in 16.02%. 3522 were treated with SBRT alone. 573 patients also received supplemental external beam radiation (median dose 4500cGY) and 1030 patients (25.15%) received Androgen Deprivation Therapy (ADT) as part of their treatment. At 75 months the 6-year biochemical relapse free survival was 95.83% in younger patients compared to 98.41% in older patients using the Phoenix definition of biochemical failure. The 6-year median post treatment PSA was 0.3 in younger patients and 0.2 in the older patients. There were no significant differences in the risk stratification between the 2 groups. This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With updated 6-year follow up, SBRT remains an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Advanced Hepatocellular Carcinoma Patients with Poor Access to Systemic Therapy Treated with Definitive Stereotactic Body Radiation Therapy: A Single-Institution Experience in Latin America

The standard treatment for patients with advanced hepatocellular carcinoma (aHCC) is systemic therapy with or without stereotactic body radiation therapy (SBRT). We present our experience using SBRT as a definitive treatment for aHCC patients with poor access to systemic therapy. We performed a retrospective review of patients treated with SBRT at the largest institution in Santiago, Chile between June 2016 and September 2022. All patients were deemed unsuitable for another locoregional treatment by the tumor board. We registered demographic, clinical and treatment characteristics. Additionally, treatment response rates using mRECIST criteria, overall survival (OS), local control (LC) and treatment toxicity were reported. We performed a multivariate analysis of variables using Cox proportion hazard ratio for OS and logistic regression for LC. A total of 59 patients were included (41 males and 18 females; median age: 70 years [range: 38 - 85 years]), with a total of 63 treatment courses. Most common etiologies of chronic liver disease were nonalcoholic fatty liver disease (23%) and chronic alcohol consumption (20%). Most patients were classified as Child-Pugh Class A (80%). Barcelona Clinic Liver Cancer (BCLC) stage was 2%, 11%, 49% and 38% for stages 0, A, B and C, respectively, while macrovascular invasion was present in 10 (18%) of patients. Forty-six patients (73%) had been subjected to prior locoregional therapy and only 5 patients (8,5%) received systemic therapy after SBRT. Median tumor size was 7 cm. (range: 0.95 - 32 cm). Median radiation dose was 40 Gy (range: 26.5 - 50 Gy) in 5 fractions. Evaluation of radiological response was performed in 46 patients (79%), with complete response, partial response, stable disease and progressive disease in 41%, 43%, 7% and 9% of the cohort, respectively. With a median follow-up of 9 months (range: 0 - 58), 34 patients (58%) died with a median OS of 10.8 months (range: 0 - 28 months). At 12 months, OS was 65.2% (95% CI: 50.9 - 76.3) and at 24 months was 40.7% (95% CI: 26.2 - 54.6) In multivariate analysis tumor size (as a continuous variable) was the only significant variable for LC (OR 2.9 [CI 1.1 - 5.3; p 0.03]) and for OS (HR 3.4 [CI 1.3 - 6.7; p< 0.01]). Four patients developed grade 3 toxicity (3 thrombocytopenia and 1 duodenal ulcer) and only two treatments were suspended definitively. Despite systemic therapy is the standard treatment for aHCC, a minor proportion of patients received the standard of care. SBRT is safe, feasible and a well-tolerated treatment option for aHCC with good clinical outcomes. To our knowledge, this is the first cohort reported of patients with aHCC treated with SBRT in Latin America.

Sinoatrial Node Irradiation in Patients Undergoing Definitive Stereotactic Body Radiation Therapy (SBRT) for Central Lung Cancers

The clinical consequences of sinoatrial node (SAN) and atrioventricular node (AVN) irradiation in patients undergoing thoracic stereotactic body radiation therapy (SBRT) remains unclear. We examined the relationship between SAN and AVN dose with survival outcomes in patients with central non-small cell lung cancer (NSCLC) tumors. A single-institutional retrospective review of patients with primary NSCLC undergoing definitive SBRT for centrally located tumors from February 2007 to December 2021 was performed. Central tumors were defined as within 2 cm of the proximal airway, mediastinum, great vessels, or spinal cord whereas ultracentral tumors were directly abutting any of the above structures. All patients underwent five-fraction SBRT to a total dose of 50 to 60 Gy. The SAN and AVN were contoured in accordance with a published contouring atlas and the maximum dose (Dmax) and mean dose (Dmean) for each structure were calculated. Sequential log rank testing between the 50th and 90th percentiles was used to identify potential cutoff values for the corresponding dosimetric parameters and non-cancer associated survival. Among 93 eligible patients, the median age was 72.5 years (Inter-Quartile Range [IQR], 66.6-78.3), median follow up was 32.4 months (IQR, 13.0-49.6), and 48 patients were female (52%). There were 49 ultracentral tumors (53%) and the median planning target volume (PTV) was 31.0 cc (IQR, 18.0-53.3). The median SAN Dmax and Dmean were 95 cGy (IQR, 37-1,072) and 58 cGy (IQR, 26-641), respectively. The median AVN Dmax and Dmean were 45 cGy (IQR, 19-506) and 34 cGy (IQR, 15-160), respectively. Candidate cutoff values for SAN Dmax and Dmean were 1,309 cGy and 814 cGy, respectively. No significant cutoff values were identified for either AVN parameter. Kaplan-Meier analysis for the proposed SAN Dmean constraint was significantly associated with overall (p = 0.016) and non-cancer associated survival (p = 0.028). The SAN Dmax constraint was significantly associated with only overall survival (p = 0.029). In a multivariate model, the SAN Dmean cutoff significantly correlated with both overall (Hazard Ratio [HR] 2.1 [1.13-3.78], p = 0.019) and non-cancer associated survival (HR 2.39 [1.12-5.10], p = 0.025) whereas the SAN Dmax cutoff was only significantly associated with overall survival (HR 1.95 [1.03-3.68], p = 0.041). SAN Dmax and Dmean were associated with significantly worse overall survival using cut-off values of 1,309 cGy and 814 cGy, respectively. SAN dose should be considered in radiation planning and further study on the consequence of SAN irradiation during SBRT is warranted.

Pre-Treatment Trends in Child-Pugh Score as an Indicator of Post-Treatment Survival in Patients Receiving Liver SBRT for HCC

We sought to understand the value of Child-Pugh (CP) score trends prior to undergoing stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma in patients with advanced cirrhosis, as an indicator of post-treatment morbidity and mortality. We hypothesize that an uptrend in CP score prior to RT increases risk of post-treatment cirrhosis progression, or death. We retrospectively reviewed all patients who underwent definitive SBRT for HCC between 2014-2022 in our health system. Most patients were referred for treatment in the 2nd or 3rd line setting, allowing us to determine CP score at multiple points before SBRT. Response to treatment was evaluated with RECIST or mRECIST criteria. Acute treatment toxicities were assessed by CTCAE v5. OS was assessed using the Kaplan-Meier method, and differences between groups were evaluated using log-rank test. A total of 61 patients were identified, 26 had an immediate pre-SBRT CP score of A5, 11 with A6, 10 with B7, 4 with B8, 4 with B9, 5 with C10, and 1 with C11. Median prescribed dose was 40Gy in 5fx. Median OS of all patients was 24 months. When stratified by CP category, median OS for CP A was not reached (NR) at time of analysis, CP B had a median OS of 14.8mo, and CP C with 1.9mo (p < 0.01). Local control rate at 6mo was 87.5%. 5 patients (8.3%) had CTCAE grade 2 acute toxicity. 10 patients had CP score progression of 2pts or more within 6mo after treatment, and 7 patients had a cause of death attributed to end stage liver disease. Median time interval between HCC diagnosis and start of RT was 338 days. In this time interval, patients with a CP score increase of 2 pts or more prior to starting RT had a median OS of 362 days, compared to NR for patients without increase (p = 0.02). When excluding the CP A group, patients with 2 pt increase had median OS of 362 days vs 445 days (p = 0.34). Again excluding the CP A group, patients with a 1 pt increase had median OS of 362 days vs NR (p = 0.23). Of 9 patients who had a pre-RT CP score increase of 2 pts or more, 7 experienced continued CP progression after treatment. In this multi-institutional retrospective analysis, we found 24 patients with advanced CP B/C cirrhosis who underwent SBRT, none of whom received orthotopic liver transplant. While CP C patients did relatively poorly, we find that some patients with CP B cirrhosis may tolerate SBRT well with good oncologic effect. When taking pre-treatment CP score increase into consideration, we saw a trend but no statistical significance indicating that a pre-SBRT increase in CP score may be associated with worse OS after treatment among CP B/C patients. We conclude that there may be a subset of patients with advanced cirrhosis who, if well selected, are appropriate candidates for SBRT. We suggest a novel use of the CP score and pre-RT trends as an additional clinical tool to aid in decision making when selecting patients. We also suggest that patients with marked up-trending scores pre-treatment have a high likelihood of continued cirrhosis progression after treatment.

Utility of Stereotactic Body Radiation Therapy (SBRT) in Establishing Local Control for Invasive Breast Cancer Patients Not Undergoing Definitive Surgery

Breast cancer (BC) treatment involves a multi-modal approach where surgical resection is the backbone of therapy. However, due to medical comorbidities precluding surgery, unresectable disease, or patient preference, some patients do not undergo surgery. In the absence of resection, it is paramount to improve local control (LC) of the primary tumor. To that end, this study explored the role of ablative RT dose delivered with SBRT. Between 2015-2022, 21 patients (10 metastatic, 11 stage IA-IIIC) received 23 SBRT courses to primary BC lesions without planned surgery at our institution. One patient had undergone whole breast RT 20 years prior to SBRT. 7 patients were analyzed retrospectively; 15 are currently enrolled in a prospective study. SBRT dose was 40 Gy/5 fractions delivered every other day. Follow-up imaging (PET, CT, MRI, MMG/US) was reviewed to evaluate the response. CTCAE v.3 was used to document any acute (≤3 months) and late toxicities. Kaplan-Meier curves were used to estimate local control (LC) and overall survival (OS). Median age was 78.4 (45.9-97.3) years. Median follow-up was 14.7 (3.3-70.3) months after RT completion. Initial post-treatment imaging was available for all cases and was performed at a median of 4.0 (0.6-11.9) months after SBRT. The median pre-SBRT index lesion size was 3.1 (0.5-14.5) cm and PTV was 32.4 (11.5-522.4) cc. At a median 4 months post-SBRT, the median decrease in index lesion size was 20.8 (0-100) % and SUV reduction was 65.2 (20.8-100) %. Further improvement was seen on the 2nd follow-up scans at a median 7.8 months post-SBRT, with 62 (0-100) % and 88 (33.3-100) % median reduction in the tumor size and SUV, respectively, compared to pre-SBRT values. The estimated LC rate was 100% at 6 months and 93.3% at 12 months. The sole case of local progression occurred 9.5 months after SBRT, after an initial interval decrease in the primary lesion. Among the patients with available systemic follow-up scans, regional progression occurred in 4 (17.4%) cases at a median 18.6 (5.2-22.7) months post-SBRT. Six (37.5%) patients developed distant progression at a median 4.8 (0.9-16.2) months, all of whom had metastatic disease at diagnosis. The estimated OS was 85.7% at 6 months and 63.8% at 12 months. Most patients tolerated the treatment well. There was no grade 4 toxicity. Complete acute toxicity data is presented in Table 1. Only one patient experienced late grade 2 breast edema. Based on our preliminary results, definitive SBRT to the primary BC appears to have a role in providing LC in the treatment of non-surgical patients and is well-tolerated. Since the disease progression tends to occur outside the treated primary tumor, additional approaches to improve regional and distant control should be investigated.

Pathologic Nodal Staging Before SBRT for Early-stage NSCLC Does Not Impact Overall Survival: A Propensity Score-matched NCDB Analysis.

Stereotactic body radiation therapy (SBRT) for early-stage non-small cell carcinoma of the lung (NSCLC) is increasingly utilized. We sought to assess overall survival (OS) for early-stage NSCLC patients receiving SBRT depending on staging method. Early-stage NSCLC patients treated with definitive SBRT were identified in the National Cancer Database (NCDB), and OS was determined based on method of staging. Patient, disease, and treatment characteristics were also analyzed. A total of 12,106 patients were included; 865 (7%) received invasive staging (nodal sampling, NS) and 11,241 (93%) had no nodal sampling (NNS). From this larger dataset, a propensity score matching (1:1 without replacement) was performed, which yielded 839 patients for each group (NNS and NS). With a median follow-up time of 3.12 years, median survival for all patients included in the matched dataset was 2.75 years (95% CI: 2.55-2.93y), with 2- and 5-year OS estimated at 63.9% and 25.7%, respectively. In a multivariable analysis on matched data, there was no difference in mortality risk between the NNS and NS groups (hazard ratio=1.08, 95% CI: 0.94-1.24, P =0.25). Negative prognostic factors identified in the multivariable analysis of the matched data included: age more than 65, male sex, Charlson-Deyo Score ≥1, and tumor size ≥3cm. SBRT use in early-stage NSCLC steadily increased over the study period. Most patients proceeded to SBRT without nodal staging, conflicting with National Comprehensive Cancer Network (NCCN) guidelines which recommend pathologic mediastinal lymph node evaluation for all early-stage NSCLC cases, except stage IA. Our findings suggest similar OS in patients with early-stage NSCLC treated with SBRT irrespective of nodal staging. Furthermore, we highlight patient-related, disease-related, and treatment-related prognostic factors to consider when planning therapy for these patients.

Definitive Stereotactic Body Radiation Therapy in Early-Stage Solitary Hepatocellular Carcinoma: An Australian Multi-Institutional Review of Outcomes

AimsStandard curative options for early-stage, solitary hepatocellular carcinoma (HCC) are often unsuitable due to liver dysfunction, comorbidities and/or tumour location. Stereotactic body radiation therapy (SBRT) has shown high rates of local control in HCC; however, limited data exist in the treatment-naïve, curative-intent setting. We report the outcomes of patients with solitary early-stage HCC treated with SBRT as first-line curative-intent therapy. Materials and methodsA multi-institutional retrospective study of treatment-naïve patients with Barcelona Clinic Liver Cancer stage 0/A, solitary ≤5 cm HCC, Child-Pugh score (CPS) A liver function who underwent SBRT between 2010 and 2019 as definitive therapy. The primary end point was freedom from local progression. Secondary end points were progression-free survival, overall survival, rate of treatment-related clinical toxicities and change in CPS >1. ResultsIn total, 68 patients were evaluated, with a median follow-up of 20 months (range 3–58). The median age was 68 years (range 50–86); 54 (79%) were men, 62 (91%) had cirrhosis and 50 (74%) were Eastern Cooperative Oncology Group 0. The median HCC diameter was 2.5 cm (range 1.3–5) and the median prescription biologically effective dose with a tumour a/b ratio of 10 Gy (BED10) was 93 Gy (interquartile range 72–100 Gy). Two-year freedom from local progression, progression-free survival and overall survival were 94.3% (95% confidence interval 86.6–100%), 59.5% (95% confidence interval 46.3–76.4%) and 88% (95% confidence interval 79.2–97.6%), respectively. Nine patients (13.2%) experienced grade ≥2 treatment-related clinical toxicities. A rise >1 in CPS was observed in six cirrhotic patients (9.6%). ConclusionSBRT is an effective and well-tolerated option to consider in patients with solitary, early-stage HCC. Prospective, randomised comparative studies are warranted to further refine its role as a first-line curative-intent therapy.

Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (SBRT).

Patients with lung cancer sometimes present with multiple primary lung cancers (MPLCs), either simultaneously (synchronous) or after treatment of an initial lesion (metachronous). Although open surgery remains a treatment mainstay for patients with stage I-II non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) is an acceptable alternative for patients who are medically unfit for or who refuse surgery. In this study, we retrospectively examine the outcome among patients with early-stage MPLCs treated at our institution with SBRT. Patients at our institution receiving SBRT for MPLC between June 2011 and March 2020 were reviewed retrospectively. Prior to undergoing definitive SBRT, the imaging, and pathology for every patient were reviewed in a multi-disciplinary thoracic/pulmonary tumor board. Dose and fractionation varied with the most common prescriptions being 50 Gy/5 fractions, 56 Gy/4 fractions, and 55 Gy/5 fractions. A total of 38 patients with a total of 80 MPLCs were treated, among which 68 were T1 lesions and 12 were T2 lesions. Median follow-up was 25.9 months, with local control (LC) rates calculated per lesion to be 98.6%, 93.3%, and 88.2% at one, two, and three years. Median overall survival (OS) was 43.5 months; 83.6%, 67.8%, and 52.3% at one, two, and three years, respectively. Sixty-two of the 80 (77.5%) treated lesions were not associated with any subsequent acute or late toxicity. The 18 (22.5%) lesions associated with toxicity included nine acute and nine late events. All toxicity was either grade 1 (13 of 18) or grade 2 (five of 18). SBRT for early-stage MPLC achieves high control rates with limited toxicity. MPLC patients deemed unfit for open surgical management should be considered for definitive SBRT.

Retrospective comparison between definitive stereotactic body radiotherapy and radical surgery for 538 patients with early-stage non-small cell lung cancer in a single institution.

Survival information for stereotactic body radiotherapy (SBRT) and surgery for stage I non-small cell lung cancer (NSCLC) was examined. Stage I NSCLC patients who underwent surgery or SBRT between 2012 and 2016 were retrospectively enrolled in this single-institution study. Using the Kaplan--Meier method and Cox regression model, overall survival (OS) was estimated and compared. Among 538 enrolled patients, compared to the surgery group (443), the SBRT group (95) had more complications (P = 0.01), worse performance status (P = 0.001), and were older (P < 0.001). Three-year OS was 70.5% post SBRT and 90.1% postsurgery. The 3-year cancer-specific survival (CSS) and disease-free survival (DFS) post SBRT and postsurgery were 92.7% vs. 92.3% and 61.1% vs 79.3%, respectively. Three-year locoregional and distant control rates post SBRT and postsurgery were 85.6% vs. 90.1% and 82.5% vs. 86.4%, respectively. Multivariate analysis using the Cox model, including age, T-stage, CCI, and C/T ratio and treatment, showed the surgery group's OS to be significantly superior to that of the SBRT group (HR of SBRT per surgery: 1.90, 95%CI: 1.12-3.21, P = 0.017). No significant differences were observed in rates of adverse events. Although OS was better in the surgery group, no differences in CSS existed. This analysis suggests the need for future studies that compare specific radical surgeries and SBRT in a prospective and randomized setting.

Right Atrial Dose is Associated with Worse Outcome in Patients Undergoing Definitive Stereotactic Body Radiation Therapy for Central Lung Tumors

<h3>Purpose/Objective(s)</h3> The consequence of cardiac substructure irradiation in patients receiving stereotactic body radiation therapy (SBRT) is not well characterized. We hypothesize that dose to the cardiac substructures is associated with outcome in this patient population <h3>Materials/Methods</h3> We reviewed the charts of patients with central lung tumors managed by definitive SBRT from June 2010-April 2019. All patients were treated with 5 fractions, typically either 5000cGy or 5500 cGy. Via a multi-patient atlas, fourteen cardiac substructures were autosegmented, manually reviewed and analyzed using dosimetric parameters. To identify relationships between dose and outcome, continuous values of each dosimetric parameter were evaluated for significant associations with non-cancer associated survival via Cox regression. Candidate constraint values were identified via dichotomization of observed values between the 20th and 95th percentile of the selected variable and compared the risk of non-cancer deaths between two groups by log-rank tests. <h3>Results</h3> A total of 83 patients were included with a median follow up of 33.4 months. Univariate Cox regression analysis identified significant relationships between D45% dose to the right atria and ventricle and non-cancer associated survival with sequential log-rank testing identifying candidate cutoff values of 890.3cGy and 564.4cGy respectively. Kaplan Meier analysis using the reported cutoff values found the D45% right atria constraint to be significantly associated with non-cancer associated (p=<0.001) and overall survival (p=<0.001) but not the right ventricle constraint. Within a multivariate model incorporating relevant clinicopathologic variables and proximal airway dose constraints, the proposed right atria D45% cutoff remained significantly correlated with non-cancer associated survival (Hazard's Ratio (HR)=8.5, 95% confidence interval (CI) 1.1-64.5, p=0.04) and OS (HR= 6.1, 95% CI 1.0-36.8, p=0.04). <h3>Conclusion</h3> Dose to D45% of the right atria significantly correlated with outcome and the candidate constraint of 890cGy stratified non-cancer associated and overall survival. Inclusion of these findings with previously characterized relationships between proximal airway constraints and survival enhances our understanding of why centrally located tumors are high risk and potentially identifies key constraints in organ at risk prioritization.

Multi-Institutional Dosimetric Analysis of Toxicity from Definitive SBRT in Cervical Cancer

<h3>Purpose/Objective(s)</h3> Brachytherapy is standard of care in locally advanced cervical cancer. In patients unable to undergo brachytherapy due to complex medical comorbidities, technical reasons, or refusal, treatment with stereotactic body radiotherapy (SBRT) is an option. We report a retrospective analysis of dosimetric parameters and toxicities for definitive cervix patients who received SBRT boost across three institutions. <h3>Materials/Methods</h3> Eligible patients had FIGO IB2-IVB cervical cancer and did not receive brachytherapy. Patient were treated with concurrent chemotherapy and pelvic external beam (EBRT) followed by SBRT with patient immobilization and fiducial image guidance. GTV and HR-CTV were defined according to EMBRACE II guidelines for brachytherapy. Clinicopathological data, dosimetric data, toxicity (CTCAE V 4.0), and outcome data was collected. Spearman correlations completed in R v4.2.1. <h3>Results</h3> 95 patients were included. All patients received EBRT to the pelvis with doses ranging from 45- 51.75Gy in 25-29 fx. SBRT doses to HR-CTV ranged from 16.8-40 Gy given in 4-6 fractions. Median (IQR) HR-CTV volume was 72.6 (58.7). The median total EQD2 were 104.25 (20.3) and SBRT EQD2 60 (20.3). Total EQD2 to 2cc of rectum and bladder were 65.67 (11.9) and 75.8 (21.5). Rates of acute and late grade 1-2 and grade 3 toxicities are reported in Table 1; there were no grade 4+ toxicities. Low grade urinary frequency was the most common reported toxicity and decreased over time. GU stricture (ureteral) was the most common acute grade 3 toxicity and was correlated with EQD2 of EBRT, SBRT, and total dose (P < 0.001), in addition to bladder 2cc SBRT (p = 0.04) and total EQD2 (p=0.02). Fistulas were rare, though some grade 3 fistula occurred. Acute grade 1-2 recto-vaginal fistulas were correlated with EQD2 of EBRT (P < 0.01), SBRT (p= 0.02), and total EQD2 (p=0.02). Late grade 3 fistulas were significantly correlated with HR-CTV volume, EQD2 of EBRT and SBRT (p=0.01) in addition to rectum 2cc SBRT dose (p=0.012), SBRT EQD2 (p=0.01), and total EQD2. <h3>Conclusion</h3> These data suggest that higher bowel/bladder 2cc SBRT and higher total EQD2 is associated with greater rates of acute and late grade 3 bowel and bladder toxicity in a cohort of women receiving SBRT for cervical cancer. Overall rates of ≥ grade 3 toxicities were small and SBRT can be a safe option for patients who cannot receive standard of care brachytherapy, especially when careful attention is given to D2cc volumes.

Four-year quality-of-life outcomes in low- to intermediate-risk prostate cancer patients following definitive stereotactic body radiotherapy versus management with active surveillance.

To review quality-of-life (QoL) metrics between patients who underwent definitive stereotactic body radiotherapy (SBRT) versus active surveillance (AS) for management of low- to intermediate-risk prostate cancer (PCa). A prospectively maintained PCa database was reviewed containing results of patient-reported QoL surveys. Patients with localized disease who chose AS or SBRT and completed at least one survey within four years of treatment were included. Patients who received salvage therapy were excluded. Survey results were compared across time using mixed-effects repeated measures analysis of covariance models that adjusted for factors significant in univariate analysis. A group x time interaction effect was examined to compare rate of change over time between AS and SBRT. P < 0.05 was significant. 148 AS and 161 SBRT patients were included. Significantly more SBRT patients had intermediate-risk disease (p < 0.0001). AS had significantly worse sexual function compared to SBRT across time. While not significant, bowel function scores were lower for SBRT patients across time points. SBRT patients had significantly lower anxiety than AS patients at 24months (p < 0.011) and 36months (p < 0.010). Urinary function though worse in SBRT patients at 12months in EPIC, was not significantly different in both groups across time points. SBRT patients have excellent QoL compared to AS with regard to anxiety post treatment. Though SBRT patients initially have worse urinary and bowel function than AS, scores were eventually similar in both cohorts by 48 months. SBRT patients have significantly worse sexual function post treatment. This study may help facilitate counseling in patients choosing PCa treatment.

Minimal residual disease (MRD) detection by ctDNA in relation to radiographic disease progression in patients with stage I-III non–small cell lung cancer (NSCLC) treated with definitive radiation therapy.

8540 Background: The standard of care for patients with inoperable early stage or locally advanced NSCLC is definitive stereotactic body radiotherapy (SBRT) or conventional radiation therapy (RT) with systemic therapy. Circulating tumor DNA (ctDNA) testing can be used for the assessment of MRD and predict risk of recurrence. Few studies have prospectively evaluated MRD detection and ctDNA dynamics specifically among patients with early or locally advanced NSCLC receiving definitive RT. Methods: In a prospective clinical cohort of patients with stage I-III NSCLC (n = 17), serial plasma samples (n = 70) were collected before and after SBRT as well as before, during, and after conventional RT with or without concurrent systemic therapy and adjuvant durvalumab. Patients were followed-up for a median of 29 months (range: 4 to 54 months) with the last serial plasma collected at a median of 5 months from completion of RT (range: 1 – 26 months). A personalized, tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA and tracked 16 tumor variants among 16 patients and 15 tumor variants in one patient. This study evaluated the prognostic value of ctDNA, correlating MRD status with clinical outcomes, in addition to ctDNA clearance kinetics during RT. Results: Among 17 patients with early-stage and locally advanced NSCLC, baseline ctDNA was detected in 82% of patients (14/17). Clinical progression was confirmed radiographically for 53% (9/17). All events of clinical progression were detectable by ctDNA (sensitivity 100%, 0.63 – 1.0), with a median lead-time of 5.5 months for MRD detection compared to radiographic disease progression. Durable ctDNA clearance was observed in 29% (5/17) of patients, all of whom then remained recurrence-free until the end of follow-up (median 12 months; specificity 100%, 95% CI 0.6 – 1.0). Transient ctDNA clearance was observed in 3 patients, and recurrent ctDNA was detected before or at the time of disease progression in all 3. ctDNA status after treatment at a single time point and longitudinally were highly predictive of disease recurrence (p &lt; 0.0001). Conclusions: ctDNA detection is feasible for patients with stage I-III NSCLC undergoing definitive chemoradiation. and can serve as a powerful predictive biomarker for disease recurrence. High baseline detection rate is essential for feasibility of a ctDNA-based MRD assay. Residual detectable ctDNA represents a powerful predictive tool to identify patients who might benefit from intensification of adjuvant therapy following definitive RT.

Right Atrial Dose Is Associated with Worse Outcome in Patients Undergoing Definitive Stereotactic Body Radiation Therapy for Central Lung Tumors

Simple SummaryThe clinical consequences of irradiating the cardiac substructures during stereotactic body radiation therapy (SBRT) remains unclear. We evaluated 83 lung cancer patients who underwent SBRT for early stage lung cancer. Using specialized software, we generated structures for fourteen cardiac substructures and evaluated radiation dose parameters for each. Among these parameters, the dose to 45% (D45%) of either the right atria or ventricle was associated with worse non-cancer associated survival with an identified cutoff value of 890 cGy and 564 cGy for each, respectively. Via these cutoffs, the D45% to the right atria, not the right ventricle, was associated with worse non-cancer associated and overall survival. Based on these findings, reducing the dose to the right atria during SBRT may improve patient outcomes in at risk patients.The consequence of cardiac substructure irradiation in patients receiving stereotactic body radiation therapy (SBRT) is not well characterized. We reviewed the charts of patients with central lung tumors managed by definitive SBRT from June 2010–April 2019. All patients were treated with five fractions, typically either 5000 cGy (44.6%) or 5500 cGy (42.2%). Via a multi-patient atlas, fourteen cardiac substructures were autosegmented, manually reviewed and analyzed using dosimetric parameters. A total of 83 patients were included with a median follow up of 33.4 months. Univariate Cox regression analysis identified a D45% dose to the right atria and ventricle for further study. Sequential log-rank testing evaluating an association between non-cancer associated survival and D45% dose to the right atria or ventricle and association was employed, identifying candidate cutoff values of 890.3 cGy and 564.4 cGy, respectively. Kaplan–Meier analysis using the reported cutoff values found the D45% right atria constraint to be significantly associated with non-cancer associated (p ≤ 0.001) and overall survival (p ≤ 0.001) but not the right ventricle constraint. Within a multivariate model, the proposed right atria D45% cutoff remained significantly correlated with non-cancer associated survival (Hazard’s Ratio (HR) ≤ 8.5, 95% confidence interval (CI) 1.1–64.5, p ≤ 0.04) and OS (HR ≤ 6.1, 95% CI 1.0–36.8, p ≤ 0.04). In conclusion, a dose to D45% of the right atria significantly correlated with outcome and the candidate constraint of 890 cGy stratified non-cancer associated and OS. The inclusion of these findings with previously characterized relationships between proximal airway constraints and survival enhances our understanding of why centrally located tumors are high risk and potentially identifies key constraints in organ at risk prioritization.

Prediction of Regional and Distant Failure After Definitive Thoracic Stereotactic Body Radiation Therapy (SBRT) Using Pre-Treatment CT-Based Radiomic Analysis

<h3>Purpose/Objective(s)</h3> Patients with early-stage non-small cell lung cancer (NSCLC) have the option of either lobectomy or definitive SBRT, both of which provide excellent local control. However, a tangible portion still suffer regional failure (RF) in the lymph nodes (LNs), or distant failure (DF) outside the thorax. Those receiving SBRT are at a further disadvantage as a LN dissection can identify occult nodal spread at the time of surgery. Thus predicting the risk of RF/DF, particularly for those treated with SBRT, remains an essential issue. Here we seek to assess whether CT-based radiomics (quantitative, sub-visual cues) could provide such insight. <h3>Materials/Methods</h3> We identified patients who received definitive lung SBRT between 2014-2019, had a pre-treatment CT chest (CT1) within 3 months prior, and had at least 12 months of follow-up. Charts were assessed for RF and DF. A pre-trained U-Net model was used to segment right and left lungs from CT1 for radiomic feature extraction. 304 radiomic signatures (Gabor wavelet, Haralick, and CoLlAGe) were extracted, filtered, and used to train Linear Discriminant Analysis (LDA) machine learning classifiers for RF and DF prediction tasks. Features from the ipsilateral (Ip) and contralateral (Con) lung were analyzed separately to assess for their comparative utility. Leave-one-out cross validation method was utilized. To serve as a control, a baseline LDA classifier was trained using canonical clinical features (Clin) including performance status, tumor stage, age, and tumor location. <h3>Results</h3> 89 stage I-II NSCLC patients with 90 lesions who received definitive SBRT were included. Median dose was 48 Gy (range: 40-54 Gy) in 3-5 fractions, prescribed to the 100% isodose line. RF was identified in 12 (13%) lesions, while DF was found in 21 (23%) lesions. Radiomic features significantly outperformed the baseline approach in both RF (AUC=0.65 vs. 0.46) and DF (AUC=0.66 vs. 0.57). There was no significant difference between features from the ipsilateral vs. contralateral lung. <h3>Conclusion</h3> CT-based radiomic analysis predicted RF and DF more accurately than clinical features alone. The similar performance between the ipsilateral and contralateral lung suggests there may be features intrinsic to the parenchyma contributing to disease recurrence. Further studies should assess whether different ROIs, including the hilum/mediastinum or peritumoral region, are more informative.