Utilization Of Stereotactic Body Radiation Therapy Research Articles

Stereotactic body radiotherapy is an alternative to radiofrequency ablation for single HCC ≤5.0 cm

Background & AimsRadiation therapy has been refined with the increasing evidence of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤ 5.0 cm. MethodsPatients with a single HCC lesion ≤ 5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate (CLRR/CDRR), progression-free survival (PFS), overall survival (OS), adverse events (AEs) and subsequent treatments after recurrence were analyzed. ResultsA total of 288 patients received RFA (166) or SBRT (122) were enrolled. The baseline characteristics between the two groups were comparable. The CLRR in the SBRT group was significantly lower than that in the RFA group (HR = 0.30, 95%CI = 0.16 – 0.57, P < 0.001), especially for patients with tumors > 2.0 cm (HR = 0.20, 95% CI = 0.08 – 0.50, P < 0.001) or adjacent to major vessels (HR = 0.29, 95% CI = 0.13 – 0.66, P < 0.001). CDRR, PFS and OS showed no significant differences between the two groups (all P > 0.050). AEs were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and TB increase. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (P < 0.001). ConclusionsBoth RFA and SBRT were effective and safe for HCC with a single lesion ≤ 5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumors > 2.0 cm or adjacent to major vessels. Impact and implicationsStereotactic body radiation therapy (SBRT) may be used as an alternative therapy to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumors > 3 cm and those with 1 to 3 tumors. This study focused on HCC patients with specific tumor burden, a single lesion ≤ 5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumors > 2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting for the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.

Racial Disparities in the Utilization of Stereotactic Body Radiation Therapy (SBRT) in Patients with Hepatocellular Carcinoma

SBRT has now been demonstrated to improve OS, PFS and TTP in patient with hepatocellular carcinoma (HCC) when compared to systemic therapy alone. Disparities in the availability and utilization of SBRT for minority racial patients may affect oncologic outcomes. This study examines racial and sociodemographic disparities in the utilization of SBRT for HCC patients. In this registry-based cohort study, data from the American College of Surgeons National Cancer Database (NCDB) from 2004 - 2017 was analyzed. Adults with a new diagnosis of localized, non-metastatic, HCC were included in this analysis. Patients were sub-grouped by race and whether they were treated with liver SBRT. In this analysis, SBRT was defined as radiation delivered in 3-5 fractions and in the 30-60Gy range. The primary outcome of this study was the utilization rate of liver SBRT in HCC, depending on race. Survival was also examined in these patients. Statistical analysis was performed using SPSS v28 for univariate and multivariate logistical regression and Kaplan-Meier analysis. From 2004 - 2017, 95132 cases of localized HCC were identified in patients who were white, non-Spanish, non-Hispanic (WNH) and 40964 cases who were black or Hispanic/Spanish (BH). Of all these patients, only 1963 patients, or 1.4%, were treated with liver SBRT. Comparing WNH patients to BH patients, 1423 (1.5%) WNH patients were treated with SBRT and 334 (0.8%) BH patients were treated with SBRT (p<0.001). Looking at the number of patients treated with SBRT each year, there has been a yearly increase in the use of liver SBRT, from 48 patients in 2007 to 340 patients in 2017. The utilization of SBRT in WNH patients has increased at a higher rate than for BH patients over this time period. The median survival for patients with localized HCC was similar for both WNH and BH patients with a median survival of 17 months (p = 0.36). However, patients who were treated with liver SBRT had an improved median survival of 25 months for WNH patients and 34 months for BH patients (p<0.001). Overall, liver SBRT is severely underutilized for patients with localized HCC in the patient population represented in this database, and fewer BH patients are treated with liver SBRT compared with WNH patients. Liver SBRT is associated with improved survival of HCC patients in this study. With the findings of the RTOG 1112 trial, demonstrating improved OS and PFS with the use of SBRT for HCC, it is essential to adopt liver SBRT more broadly and to develop strategies to reduce the racial disparities in utilization.

Prospective Phase II Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy (SBRT) Followed By Concurrent Mediastinal Chemoradiation and Adjuvant Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer (LA NSCLC)

To report the efficacy and toxicity outcomes of a prospective phase II trial of primary tumor SBRT followed by conventional chemoradiation to the lymph nodes and adjuvant immunotherapy in patients (pts) with unresectable LA NSCLC. Eligible pts included stage II-III LA NSCLC with peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions to the involved lymph nodes with concurrent platinum doublet chemotherapy. The trial was amended to allow pts without disease progression after chemoradiation to receive adjuvant durvalumab per the PACIFIC trial. The primary endpoint was 1 year progression free survival (PFS), evaluated as a binary variable. Frequencies and proportions were used for reporting this primary endpoint, in addition to adverse events and patterns of failure. Median PFS and OS were estimated using Kaplan Meier methods. Safety and efficacy is reported on the first 50 pts enrolled in the trial with a median follow-up of 24 months (mos) (range, 1-54 mos). Pts were primarily stage IIIA (60%) or stage IIIB (34%), with 6% of pts stage IIB. Overall grade 3 or higher toxicity related to SBRT and/or mediastinal radiation was 8% with two pts (4%) developing grade 3 pneumonitis and one pt having a grade 5 lung infection possibly related to radiation. Overall grade 2 pneumonitis related to SBRT or mediastinal radiation was 20%. Only one pt (2%) developed grade 3 esophagitis. No late cardiac events have been observed. The one-year PFS for all pts was 62% with a median PFS of 26.3 mos and median overall survival of 40.8 mos. Of the 50 pts enrolled, 37 received at least one dose of adjuvant durvalumab. The one-year PFS for pts who received at least one dose of durvalumab was 70.3% with a median PFS not yet reached in this group (median follow-up 24 mos). Patterns of failure were mostly distant with 26% of pts experiencing distant failure, 6% regional, and 2% distant and regional. There was only one local failure (2%) after SBRT in all 50 pts. SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes and adjuvant immunotherapy was well tolerated and showed improved 1-year PFS compared to prior conventional chemoradiation trials for locally advanced NSCLC. The results of this trial will be further evaluated in a randomized phase III study, NRG LU-008. Pts will receive either conventional chemoradiation vs. SBRT to the primary tumor followed by chemoradiation to the involved lymph nodes followed by consolidative immunotherapy to evaluate the possibility of utilization of SBRT as a new standard of care for LA NSCLC.

Abstract CT151: A phase II study of optimized individualized adaptive radiation therapy for hepatocellular carcinoma

Abstract Introduction: Stereotactic body radiation therapy (SBRT) for the treatment of hepatocellular carcinoma (HCC) remains a challenge due to high rates of toxicity in patients with impaired liver function or tumors not amenable to thermal ablation. We performed a single-arm prospective phase II clinical trial utilizing a novel treatment paradigm optimizing the utility of SBRT based on the individual patient’s probability for tumor control traded off against the risk of liver injury. We hypothesized that maximizing the utility of treatment would decrease toxicity while achieving the same tumor control rate as standard therapy. Methods: Patients with Child-Pugh (CP) A to B7 disease with tumors &amp;gt;3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an IRB approved clinical trial to undergo SBRT with baseline dose optimization and mid-treatment response adaptation. Optimization and adaptation were based on the expected utility of treatment, calculated as a weighted average of the probability of 4 combinations of toxicity and efficacy outcomes. These calculations were based on the individual patient’s baseline indocyanine green retention at 15 minutes or albumin-bilirubin score (ALBI), CP score, intended dose and fractionation, and mean liver dose with the goal of maximizing the difference between the probability of local control compared to the probability of treatment-related toxicity. Primary endpoints were rate of liver decompensation as measured by ≥2 point change in CP score within 6 months, and lesion-specific local control. Overlap weighting was used to compare patients treated on protocol with patients receiving conventional SBRT at another high-volume cancer center. Results: 56 patients with 80 tumors met inclusion criteria and had a median follow-up of 11.2 months. 44 tumors with a median size of 3.8 cm were treated in CP-A to B7 patients, while 36 tumors with a median size of 2.1 cm were treated in CP ≥ B8 patients. Optimization resulted modification of initial dose for 38% of patients. Sixty-eight percent of patients underwent mid-treatment adaptation with either omission or dose reduction of the final two treatments based on change in expected utility. The 1 year freedom from local progression was 94%. A total of 21% of patients experienced a ≥ 2 point change in CP score within 6 months. Overlap weighted analysis revealed similar local control (HR 0.69, 95% CI [0.25-1.91], p = 0.48), and overall survival (HR 1.45, 95% CI [0.69-3.0], p = 0.33), with decreased toxicity (OR 0.26, 95% CI [0.07 - 0.99], p = 0.048) compared to conventional SBRT. Conclusion: SBRT for HCC patients with large tumors or poor liver function can be optimized via an individualized, utility-based treatment paradigm which may decrease treatment-related toxicity while maintaining tumor control. Citation Format: Daniel J. Herr, Chang Wang, Mishal Mendiratta-Lala, Martha Matuszak, Charles S. Mayo, Yue Cao, Neehar Parikh, Randy Ten Hanken, Dawn Owen, Teodor Stanescu, Michael Yan, Laura A. Dawson, Matthew Schipper, Theodore S. Lawrence, Kyle C. Cuneo. A phase II study of optimized individualized adaptive radiation therapy for hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT151.

Planning for the Effect of the SC.24 Trial on Spine Stereotactic Body Radiation Therapy Utilization at a Tertiary Cancer Center

The goal of this study was to assess the potential real-world effect of the recently reported SC.24 trial on spine stereotactic body radiation therapy (SBRT) utilization. We estimated the proportion of patients treated with conventional radiation therapy (CRT) who would have been eligible for spine SBRT per trial inclusion criteria and analyzed the potential estimated increased costs to our institution. This was a retrospective review of patients who received spine CRT at our institution between August and October 2020. Data abstracted included demographics, SC.24 eligibility criteria, provider-reported pain response, and survival. A cost analysis and time survey was performed using institutional and provincial data. Of 73 patients reviewed, 24 patients (33%) were eligible. The most common exclusion factors included irradiation of ≥3 consecutive spinal segments (n=32, 44%), Eastern Cooperative Oncology Group performance status >2 (n=17, 23%), and symptomatic spinal cord compression (n=13, 18%). Of eligible patients, the mean age was 68.92 years, median spinal instability in neoplasia score was 8 (interquartile range, 7-9), and median Eastern Cooperative Oncology Group performance status was 2 (interquartile range, 1-2). The most common primary cancer types among eligible patients were lung (n=10) and breast (n=4). The median survival of eligible patients was 10 months (95% confidence interval, 4 months to not reached) with 58% surviving longer than 3 months. Of patients who had subjective pain documented after CRT, 54% had at least some response. The cost of spine SBRT was estimated at CA$4764.80 compared with $3589.10 for CRT, and tasks for spine SBRT took roughly 3 times as long as those for CRT. One-third of patients who received palliative spine CRT met eligibility criteria for SC.24. This possible expanded indication for spine SBRT can have a substantial effect on resource utilization. These data may be useful in guiding resource planning at institutions looking to commence a spine SBRT program.

Stereotactic body radiation therapy to the kidney for metastatic renal cell carcinoma: A narrative review of an emerging concept

This narrative review provides a historical overview of cytoreductive nephrectomy for metastatic renal cell carcinoma (mRCC) and examines the safety and therapeutic potential of cytoreductive stereotactic body radiation therapy (SBRT) for mRCC in the modern immunotherapy era. In the last five years, the introduction of immune checkpoint inhibitors for the treatment of mRCC has improved outcomes for patients. This has brought forth new exploration of the role of CN in combination with immunotherapy. Early retrospective evidence suggests that there may be a benefit of deferred CN after immunotherapy (IOT) for de novo mRCC patients. However, there has also been concern regarding the feasibility of surgery after IOT due to inflammation. SBRT may be an appropriate alternative in these circumstances. Since 1999, cytoreductive SBRT has been used for inoperable primary RCC. Several prospective and retrospective studies treating the kidney tumor for localized RCC have shown that this technique is safe and produces favorable and durable local control. SBRT has also exhibited similar effectiveness to CN, while providing additional benefits including noninvasiveness and the ability to treat tumors that can't be treated with nephrectomy or ablation due to size or location. Furthermore, SBRT confers immunostimulatory effects, which are hypothesized to work synergistically with immunotherapy. Clinicians should consider SBRT a safe and reliable alternative to CN for RCC patients. Ongoing studies are exploring the utility of SBRT for treatment of the primary tumor in mRCC patients receiving standard of care immunotherapy.

Pattern of Radiotherapy Treatment in Low-Risk, Intermediate-Risk, and High-Risk Prostate Cancer Patients: Analysis of National Cancer Database.

In this study, the utilization rates and survival outcomes of different radiotherapy techniques are compared in prostate cancer (PCa) patients stratified by risk group. We analyzed an extensive data set of N0, M0, non-surgical PCa patients diagnosed between 2004 and 2015 from the National Cancer Database (NCDB). Patients were grouped into six categories based on RT modality: an intensity-modulated radiation therapy (IMRT) group with brachytherapy (BT) boost, IMRT with/without IMRT boost, proton therapy, stereotactic body radiation therapy (SBRT), low-dose-rate brachytherapy (BT LDR), and high-dose-rate brachytherapy (BT HDR). Patients were also stratified by the National Comprehensive Cancer Network (NCCN) guidelines: low-risk (clinical stage T1-T2a, Gleason Score (GS) ≤ 6, and Prostate-Specific Antigen (PSA) &lt; 10), intermediate-risk (clinical stage T2b or T2c, GS of 7, or PSA of 10-20), and high-risk (clinical stage T3-T4, or GS of 8-10, or PSA &gt; 20). Overall survival (OS) probability was determined using a Kaplan-Meier estimator. Univariate and multivariate analyses were performed by risk group for the six treatment modalities. The most utilized treatment modality for all PCa patients was IMRT (53.1%). Over the years, a steady increase in SBRT utilization was observed, whereas BT HDR usage declined. IMRT-treated patient groups exhibited relatively lower survival probability in all risk categories. A slightly better survival probability was observed for the proton therapy group. Hormonal therapy was used for a large number of patients in all risk groups. This study revealed that IMRT was the most common treatment modality for PCa patients. Brachytherapy, SBRT, and IMRT+BT exhibited similar survival rates, whereas proton showed slightly better overall survival across the three risk groups. However, analysis of the demographics indicates that these differences are at least in part due to selection bias.

Increased Utilization of Stereotactic Body Radiotherapy is Associated with Decreased Disparities and Improved Survival for Early-Stage NSCLC

IntroductionWe sought to determine if increased use of stereotactic body radiation therapy (SBRT) was associated with decreased disparities in the receipt of definitive treatment for early-stage non-small cell lung cancer (NSCLC). MethodsThe National Cancer Database (NCDB) was utilized to determine the proportion of patients with NSCLC receiving surgery, SBRT, or no definitive treatment for clinical cT1-2aN0M0 NSCLC from 2004-2017. Univariable and multivariable logistic regressions were used. Age-adjusted mortality rates were calculated using the Surveillance, Epidemiology, and End Result (SEER) database. ResultsFrom 2004 to 2017, the proportion of early-stage NSCLC undergoing no definitive treatment declined from 22% to 10.5% (P<.001), while the proportion receiving SBRT increased from 1% (0.9%-1.3%) to 22% (21.4%-22.3%; P<.001). Among Whites, the proportion undergoing no definitive treatment decreased from 21% to 10% (P<.001), as compared to Blacks, which had a higher decrease, of 32% to 15% (P<.001). The proportion of Blacks receiving SBRT increased from 1% (0.3%-1.7%) to 22% (20.8%-23.5%) (P<.001). Between 2011 and 2017 likelihood of Blacksreceiving curative therapy increased compared to Whites [OR: 0.55 (0.48-0.64) to 0.70 (0.62-0.79; P<.001]. Furthermore, the age-adjusted mortality rate of early-stage NSCLC decreased from 4.3 (4.0-4.5) in 2004 to 0.8 (0.7-0.9) in 2017 (P<.001). ConclusionsIncreased utilization of SBRT significantly increased the proportion of patients receiving curative therapy for early-stage NSCLC and was associated with an improvement in mortality. Furthermore, the use of SBRT reduced previously seen disparities in receipt of treatment between Whites and Blacks. SBRT was also associated with decreased mortality from early-stage NSCLC.

Hospital Utilization of Stereotactic Body Radiation Therapy and Rates of Surgical Refusal

BackgroundIncreasingly, stereotactic body radiation therapy (SBRT) is used for patients unfit for or unwilling to undergo operation for early-stage non–small cell lung cancer. It remains unclear how SBRT utilization has influenced patient refusal of surgical resection. MethodsA retrospective cohort analysis was completed using the National Cancer Database for patients with T1/T2 N0 M0 lesions from 2008 to 2017. Facilities were categorized into tertiles by SBRT/surgery ratio for each year of analysis. Propensity score matching was used to compare rates of surgical refusal and rates of postrefusal receipt of SBRT. Multivariable regression analysis was performed to evaluate effect size. ResultsThe study included 129 901 patients; 63 048 were treated at low-tertile SBRT/surgery facilities, 41 674 at middle-tertile SBRT/surgery facilities, and 25 179 at high-tertile SBRT/surgery facilities. Patients refusing surgery at high SBRT/surgery facilities had fewer comorbid conditions and smaller tumors. Rates of SBRT after surgical refusal differed (low SBRT/surgery facilities, 17.2%; high SBRT/surgery facilities, 55.9%; P < .001). In a matched cohort of 76 636, surgical refusal differed (low SBRT/surgery facilities, 4.2%; high SBRT/surgery facilities, 6.0%; P < .001). On multivariable regression, treatment at a top-tertile SBRT/surgery facility was the largest risk factor for surgical refusal (odds ratio, 3.82 [3.53-4.13]; P < .001) and was most strongly associated with postrefusal receipt of SBRT (odds ratio, 6.11 [5.09-7.34]; P < .001). ConclusionsPatients treated at high SBRT–using facilities are more likely to refuse surgical resection and more likely to receive radiation therapy after surgical refusal. Further analysis is needed to better understand patient refusal of surgery in the setting of early-stage non–small cell lung cancer.

Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer at Facilities With Stereotactic Body Radiation Therapy Programs

<h3>Purpose/Objective(s)</h3> Patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC) may be at high-risk for post-operative mortality. Access to stereotactic body radiation therapy (SBRT), a less invasive alternative, may facilitate more appropriate patient selection for surgery. <h3>Materials/Methods</h3> An analysis of all patients with early-stage NSCLC reported to the National Cancer Database between 2004-2015 was performed. Post-operative mortality rates were derived using vital status data. Utilization of SBRT was defined by each facility's SBRT Experience in years and SBRT-to-Surgery Volume Ratios, defined by quartiles. Multivariable logistic regression with backward elimination was used to test for the associations between facility-level SBRT utilization and post-operative mortality. Interaction testing of independent covariates was performed to assess the effect of SBRT utilization across subgroups. <h3>Results</h3> The study cohort consisted of 202,542 patients who underwent surgical resection of clinical stage T1-T2 N0 M0 NSCLC between 2004-2015. The 90-day post-operative mortality rate declined significantly during the study period from 4.6% to 2.6% (p < 0.001). During this period, the proportion of facilities that utilized SBRT increased from 4.6% to 77.5% (p < 0.001) and the proportion of patients treated with SBRT increased significantly from 0.7% to 15.4% (p < 0.001). On multivariable analysis, lower 90-day post-operative mortality rates were observed among patients who underwent resection at facilities with greater than six years of SBRT Experience (OR 0.84, CI 0.76-0.94, p = 0.003) and SBRT-to-Surgery Volume Ratios above 17% (OR 0.85, CI 0.79-0.92, p < 0.001). Additional covariates associated with 90-day mortality included higher surgical volume, geographic region, year of diagnosis, age, sex, race, insurance status, facility type, Charlson-Deyo score, clinical T stage, histology, anatomic location, surgery type, and prior malignancy. Interaction testing between these covariates was negative, demonstrating that findings were consistent across subgroups. <h3>Conclusion</h3> Patients who underwent surgical resection for early-stage NSCLC at facilities with higher SBRT Experience and SBRT-to-Surgery Volume Ratios had lower rates of post-operative mortality. These findings suggest that the availability of SBRT may improve allocation of patients to surgery or SBRT, particularly for higher-risk patients. The observation of higher post-operative mortality rates at facilities without an SBRT program merits further investigation.

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.

Surgical outcomes for early-stage non-small cell lung cancer at facilities with stereotactic body radiation therapy programs.

8538 Background: Patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC) may be at high-risk for post-operative mortality. Access to stereotactic body radiation therapy (SBRT) offers a less invasive alternative for this population that may facilitate more appropriate patient selection for surgery. Methods: An analysis of all patients with early-stage NSCLC reported to the National Cancer Database between 2004-2015 was performed. Post-operative mortality rates were derived using vital status data. Utilization of SBRT was defined by each facility’s SBRT Experience in years and SBRT-to-Surgery volume ratios, defined by quartiles. Multivariable logistic regression with backward elimination was used to test for independence of associations between exposures of interest and post-operative mortality. Interaction testing was performed to assess the statistical relationship of covariates found to have independent associations. Results: The study cohort consisted of 202,542 patients who underwent surgical resection of clinical stage T1-T2 NSCLC (AJCC 7th edition). The 90-day post-operative mortality rate declined significantly during the study period from 4.6% to 2.6% (p &lt; 0.001). During this period, the proportion of facilities that utilized SBRT increased from 3.3% to 77.5% (p &lt; 0.001) and the proportion of patients treated with SBRT increased significantly from 0.7% to 15.4% (p &lt; 0.001). Lower 90-day post-operative mortality rates were observed at facilities with greater than six years of SBRT experience (OR 0.84, CI 0.76-0.94, p = 0.003) and SBRT-to-Surgery volume ratios above 17% (OR 0.85, CI 0.79-0.92, p &lt; 0.001). Additional covariates associated with 90-day mortality included higher surgical volume, geographic region, year of diagnosis, age, sex, race, insurance status, facility type, Charlson-Deyo score, clinical T stage, histology, anatomic location, surgery type, and prior malignancy. Interaction testing between these covariates was negative, demonstrating that higher SBRT Experience and SBRT-to-Surgery volume ratios were independently associated with lower 90-day surgical mortality. Conclusions: Patients who underwent surgery for early-stage NSCLC at facilities with higher SBRT Experience and SBRT-to-Surgery volume ratios had lower rates of post-operative mortality. These findings suggest that the availability of SBRT may be a surrogate for a more comprehensive and safer approach to matching patients to surgery or SBRT. The observation of higher post-operative mortality rates at facilities without an SBRT program deserves further study.

Stereotactic body radiation therapy for early-stage non-small cell lung cancer in the USA: patterns of adoption and potential healthcare disparities

Stereotactic body radiation therapy (SBRT) is a definitive treatment option for early-stage non-small cell lung cancer (NSCLC), but access is not universal. This study evaluated trends in SBRT utilization to identify potential disparities. This was a cancer registry study using the National Cancer Database (NCDB). The NCDB was queried for patients diagnosed with early-stage NSCLC from 2004 to 2016. Patients receiving surgery, chemotherapy, radiation not meeting criteria for SBRT, or other ablative procedures were excluded. SBRT use in treatment facilities over time was evaluated, and patients were analyzed by various socioeconomic factors to determine predictors of SBRT vs no-treatment. Multivariate and Cox regression analyses were performed to determine the extent to which decreased treatment with SBRT may be contributing to worse overall survival. A total of 65,376 patients were included. There was a significant increase in SBRT use from 2004 (n = 80) to 2016 (n = 7948). Patients treated in academic centers were more likely to get SBRT than community programs, but the use in the community has increased in recent years. Covariates associated with decreased use of SBRT included lack of insurance (OR 0.45, p < 0.0001), Hispanic (OR 0.79, p < 0.001), black (OR 0.59, p < 0.0001), or ‘other’ race (OR 0.48 p < 0.0001), and living in a less-educated community (OR 0.83, p < 0.001). On multivariate analysis, use of SBRT was associated with decreased risk of death (HR = 0.48, p < 0.001), and patients treated with SBRT had increased median overall survival compared with patients receiving no treatment (39.6 versus 14.9 months, p < 0.001 by log-rank test). SBRT use is increasing across all treatment facilities but there are notable health disparities based on socioeconomic factors including race that may be contributing to worse survival outcomes.

Analysis of Stereotactic Body Radiotherapy for Head and Neck Cancer using the National Cancer Database

Recent studies have demonstrated promising results with stereotactic body radiation therapy (SBRT), usually as re-irradiation in recurrent head and neck cancer (HNC) or second primary HNC, and in patients who cannot tolerate 6-7 weeks of conventional radiotherapy. We seek to evaluate the uptake of SBRT for HNC using the National Cancer Database (NCDB) and evaluate social, clinicopathological and treatment factors impacting overall survival (OS). To evaluate the national utilization of SBRT for head and neck cancer and investigate the relationship between social demographics, clinicopathological factors, and treatment dose fractionation with overall survival. The NCDB was queried to identify 549 HNC cases undergoing SBRT from 2004 to 2015. Patients were treated in 1 (15-24Gy, n=46), 2 (7.5-12Gy, n=19), 3 (5-12Gy, n=57), 4 (5-12Gy, n=34), or 5 (4-10Gy, n=393) fractions. The biologically effective dose with α/β=10 (BED10) was calculated. A BED10 of 59.5 Gy10 using a dose/fractionation scheme of 35 Gy in 5 fractions was used as a cut point to evaluate SBRT effective dose regimens on survival. The following patient factors were analyzed: age, race, insurance status, median household income, and Charlson-Deyo Score (CDS), year of diagnosis, TNM stage category, history of cancer, and tumor site (larynx/hypopharynx, oral cavity/oropharynx/lip, sino-nasal/nasopharynx, salivary gland). Treatment factors included BED10 (<59.5 Gy10, ≥59.5 Gy10), facility type, and treatment modality (radiation only, RT; chemoradiation, CRT; surgery with radiation, S+R; surgery with chemoradiation, S+CRT). Median OS, three, and five-year survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression modeling was used to compute adjusted hazard ratios (HR) with 95% confidence intervals (CI). The median age was 70 years (interquartile range, 60-81). The majority of patients were white (84.7%, n=465), on Medicare (56.5%, n=310), and were treated at an academic treatment facility (63.2%, n=347). History of prior cancer was recorded in 39.3% of patients. The most common treatment modality was RT (43.5%, n=239) followed by CRT (24.6%, n=135), S+R (24.0%, n=134), and S+CRT (7.8%, n=43). Median follow-up in all and surviving patients was 11.9 and 29 months, respectively. A total of 436 deaths were reported, and the overall 3-year survival rate was 23.0% (median survival, 12.6 months). On multivariate analysis, older age, CDS ≥2, advancing T, and N category was associated with poor survival. Patients with a history of cancer (HR 1.40, 95% CI 1.13-1.75, p=0.003) and M1 disease (HR 2.34, 95% CI 1.73-3.15, p<0.0001) also reported poor survival. Compared to RT, improved survival was noted for CRT (HR 0.61, 95% CI 0.47-0.80, p=0.0003) and S+R (HR 0.50, 95% CI 0.37-0.69, p<0.0001) but not S+CRT. A BED10 value of ≥59.5 Gy10 was also associated with improved survival (HR 0.57, 95% CI 0.46-0.71, p<0.0001). No significant difference in survival was noted by race, insurance, income, and treatment facility. Factors adversely affecting survival in HNC patients treated with SBRT included a history of prior cancer, older age, patient co-morbidities, advanced T, N, and M stage. SBRT dose fractionation with a BED10 of ≥59.5 Gy, and combination with chemotherapy and surgery improves survival for HNC.

Stereotactic Body Radiation Therapy for Recurrent, Isolated Hepatocellular Carcinoma Lymph Node Metastasis With or Without Prior Liver Transplantation.

Lymph node metastases from hepatocellular carcinoma (HCC) represents a challenging clinical scenario with a poor prognosis, especially in the setting of prior liver transplant. Long-term survival is achievable in select patients with isolated lymph node metastases who undergo surgical resection, but little data exist regarding non-surgical options. For intrahepatic HCC, stereotactic body radiation therapy (SBRT) has emerged as a standard and effective nonsurgical treatment option. Here, we present three patients (two with prior liver transplant) with isolated lymph node metastases treated with curative intent using SBRT to doses of 30-45 Gy in three to five fractions. Two patients (with follow-up of 27 and 31 months) had a complete or near-complete response and remain cancer-free. One patient had intrahepatic HCC recurrence shortly after SBRT but stable disease in the treated lymph node metastasis at 20 months. Liver function remained excellent after radiation in all three patients, but one patient developed a grade 3 duodenal ulcer at 20 months that resolved with medical management. These cases illustrate the potential utility of SBRT as a non-invasive, definitive treatment option for patients with isolated lymph node metastases from HCC.

Impact of Travel Distance on Radiation Treatment Modality for Central Nervous System Disease.

Background Stereotactic body radiation therapy (SBRT) has emerged as a popular alternative to conventional radiation therapy (RT) over the past 15 years. Unfortunately, the impact of patient distance from radiation treatment centers and utilization of SBRT versus conventional RT has been sparsely investigated. This report represents the first analysis of the impact of patient distance on radiation treatment modality for central nervous system (CNS) disease. Materials and Methods Since the inception of our RADIation oncology And Neuro-Surgery (RADIANS) multidisciplinary clinic at a community hospital in 2016, 27 patients have received either SBRT or conventional RT as their sole radiation treatment modality for CNS disease. Twenty-four (88.9%) presented with metastatic disease. Fisher’s exact test evaluated the relationship between patient residence from treatment (in miles) and radiation treatment modality received. Results Mean patient distance from our RADIANS clinic was 50.6 miles (median = 15.3). Twenty-one patients (77.8%) received SBRT; the remaining six received conventional RT. Mean patient distance from SBRT was 63.6 miles, and mean patient distance for conventional RT was 5.1 miles; this finding was statistically significant ( p = 0.0433; 95% confidence interval = 1.9–115.1). Conclusion Our findings indicate that patients with CNS disease who receive SBRT over conventional RT are statistically more likely to reside further from treatment centers. This is similar to findings of national studies comparing proton versus photon treatment for pediatric solid malignancies. The results from our work have implications for neuro-oncology treatment and the development of community hospital-based clinic models similar to RADIANS in the future.

Temporal Trends in the Utilization of Stereotactic Body Radiotherapy for Non-Small Cell Lung Cancer in the United States

The optimal treatment of early stage non-small cell lung cancer (NSCLC) continues to evolve. Stereotactic body radiation therapy (SBRT) has become the preferred treatment modality for patients deemed medically inoperable. The trends in SBRT utilization and other treatment modalities were evaluated over time for patients with early stage NSCLC. We hypothesize that an increase in the use of SBRT for early NSCLC may be related to the increase in smaller lesion size detected in recent years. The National Cancer Database was queried for patients at least 18 years of age with pathologically proven, cT1-T3N0 and less than 5 cm in size (AJCC 7th ed.), NSCLC from 2004-2014. Patients who got chemotherapy or radiation before surgery were excluded. Patients were grouped by treatment modality (sublobar resection, lobectomy, SBRT, and no treatment). Treatment modality as a percentage of total new cases was assessed by year of diagnosis and by tumor size. A multinomial logistic regression model was used to measure the relationship between treatment modality, year of diagnosis, and tumor size, after controlling for other covariates. A total of 156,092 patients met inclusion criteria and were included in the analysis. The absolute number of cases of lobectomy and sublobar resections remained stable over 2008-2014, while SBRT cases rose over the course of the study period. The proportion of lobectomy cases decreased from 56% in 2008 to a nadir of 44% in 2014. Proportion of SBRT use increased from 1.5% to 25%, and the proportion of patients receiving no therapy declined from 27% to 13%. Mean lesion size decreased from 24.5 ± 10.8 mm (mean ± SD) to 22.5 ± 10.1 mm over the study period. In the multinomial logistic regression model, the likelihood of receiving SBRT continuously increased each year while no treatment decreased over the study period (p<0.0001) after controlling for tumor size, age, race, insurance, facility type, Charlson-Deyo score, and education. SBRT was also more likely to be used for smaller tumors compared to lobectomy (p<0.0001). Utilization of SBRT for early stage NSCLC increased significantly over the study period. Given the lack of significant change in the number of surgeries, much of the SBRT use appears to have focused on patients who would have otherwise received no therapy. The lesion size treated with SBRT decreased slightly over time, in parallel with the overall population, likely due to combination of increased incidental findings from imaging and screening efforts. This study provides important information on patterns of care for early stage NSCLC in the U.S. and identifies SBRT as an important treatment modality, especially for small tumors and for poor surgical candidates who may otherwise receive no treatment.

Recommendations for Single-Fraction Radiation Therapy and Stereotactic Body Radiation Therapy in Palliative Treatment of Bone Metastases: A Statewide Practice Patterns Survey

PurposeSingle-fraction (SF) radiation therapy is effective and convenient for patients with painful noncomplex bone metastases. Prior survey results reported a low recommendation of SF radiation therapy in the US. We sought to assess contemporary treatment recommendations for the management of bone metastases among diverse physicians participating in a statewide quality consortium. Methods and MaterialsMembers of the Michigan Radiation Oncology Quality Consortium were surveyed between April and May 2017. Physicians rated the importance of 31 variables on their choice of dose fractionation. The survey also covered 7 patient scenarios. ResultsFifty-six physicians responded who were practicing at 18 of 20 centers surveyed. Respondents recommended 23 dose-fractionation schedules across the 7 scenarios. Highest-rated factors considered when choosing a dose fractionation regimen were performance status, prognosis, spinal cord compression, and prior radiation therapy. Recommendations for SF overall were uncommon (16.1%). On multivariable analysis, factors associated with SF use included academic employment (odds ratio [OR] 2.04; 95% CI, 1.02-4.08; P = .044) and higher palliative case volume (OR 2.59; 95% CI, 1.45-4.63; P = .001). Stereotactic body radiation therapy (SBRT) was recommended in 16.4% of scenarios overall, and on multivariable analysis, significant predictors for SBRT use were academic employment (OR 2.99; 95% CI, 1.39-6.44; P = .005), more recent residency completion (OR 4.37; 95% CI, 1.26-15.17; P = .02), spine location (OR 12.54; 95% CI, 3.96-39.68; P < .001), and prior radiation therapy (OR 26.67; 95% CI, 7.86-90.57; P < .001). SF rates were higher than in a survey reported in 2009 (16.1% vs 9.4%, P = .0004). ConclusionsSF radiation therapy remains uncommonly recommended, although it may be recommended more now than it was 10 years ago despite the increased utilization of SBRT. We identify multiple key drivers in physician decision making affecting SF recommendations that have not been addressed by prior level one evidence. Further research with evidence-based recommendations to clarify the role of SF and SBRT in management of patients with bony metastases are needed.

Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma

Background: Neoadjuvant therapy is a strategy for resectable and borderline resectable pancreatic cancer, but a consensus approach regarding optimal management is undetermined. Neoadjuvant options include chemotherapy with/without radiotherapy. Stereotactic body radiation therapy (SBRT) is a novel radiation technique that may provide benefit over conventionally fractionated radiation therapy (CFRT) in the neoadjuvant setting. The purpose of the present study is to determine neoadjuvant treatment with SBRT to other neoadjuvant treatment options for patients with resectable pancreatic cancer.Material and methods: The National Cancer Database was queried (2004–2015) for patients with nonmetastatic pancreatic adenocarcinoma receiving neoadjuvant therapy followed by pancreatectomy. Patients were categorized based on the type of neoadjuvant treatment administered. Statistics included temporal trend assessment by annual percent change (APC), predictors for SBRT by multivariable logistic regression, Kaplan–Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling for univariable OS analysis.Results: Of 5828 patients, 332 (5.7%), 3234 (55.5%) and 2262 (38.8%) received neoadjuvant chemo-SBRT, chemotherapy, and chemo-CFRT, respectively. SBRT utilization increased from 0% in 2004 to 9.5% in 2015, with a greater APC after 2010 (p < .001). SBRT was more likely to be utilized in patients with T3–4 and node-positive disease (p < .05 for all). The chemo-SBRT cohort was associated with a higher OS rate before and after propensity matching (p < .05 for both). The rate of R0 resection was higher in radiotherapy groups than the chemotherapy cohort (p < .001).Conclusions: Utilization of neoadjuvant SBRT for pancreatic cancer is increasing. In the neoadjuvant setting, chemo-SBRT may improve R0 resection and OS over chemotherapy and chemo-CFRT, although confirmatory prospective studies are needed for confirmation.

P18 - Impact of Travel Distance on Radiation Treatment Modality for Central Nervous System Disease

Background Stereotactic body radiation therapy (SBRT) has emerged as a popular alternative to conventional radiation therapy (RT) over the past 15 years. Unfortunately, the impact of patient distance from radiation treatment centers and utilization of SBRT versus conventional RT has been sparsely investigated. This report represents the first analysis of the impact of patient distance on radiation treatment modality for central nervous system (CNS) disease. Materials and Methods Since the inception of our RADIation oncology And Neuro-Surgery (RADIANS) multidisciplinary clinic at a community hospital in 2016, 27 patients have received either SBRT or conventional RT as their sole radiation treatment modality for CNS disease. Twenty-four (88.9%) presented with metastatic disease. Fisher’s exact test evaluated the relationship between patient residence from treatment (in miles) and radiation treatment modality received. Results Mean patient distance from our RADIANS clinic was 50.6 miles (median = 15.3). Twenty-one patients (77.8%) received SBRT; the remaining six received conventional RT. Mean patient distance from SBRT was 63.6 miles, and mean patient distance for conventional RT was 5.1 miles; this finding was statistically significant (p = 0.0433; 95% confidence interval = 1.9–115.1). Conclusion Our findings indicate that patients with CNS disease who receive SBRT over conventional RT are statistically more likely to reside further from treatment centers. This is similar to findings of national studies comparing proton versus photon treatment for pediatric solid malignancies. The results from our work have implications for neuro-oncology treatment and the development of community hospital-based clinic models similar to RADIANS in the future.