Stereotactic Body Radiotherapy For Stage Research Articles

Artificial Intelligence-suggested Predictive Model of Survival in Patients Treated With Stereotactic Radiotherapy for Early Lung Cancer.

Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting. Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts. Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2. The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively.

The Impacts of Angiotensin Receptor Blockers (ARBs) or Angiotensin-Converting Enzyme Inhibitors (ACEIs) on Patients with Stereotactic Body Radiation Therapy (SBRT) for Early-Stage NSCLC

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as an alternative to surgery for patients with inoperable early-stage non-small cell lung cancer (NSCLC). The majority of inoperable NSCLC patients are elderly and frequently have comorbidities including cardiovascular diseases for which they frequently receive angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs). The interactions of these medications with SBRT are not clear. The objective of the current study is to investigate the interaction of ARBs and ACEIs with SBRT for the outcomes of early-stage NSCLC. Methods and Materials: A retrospective chart review of patients treated with SBRT for Stage I and II NSCLC (AJCC 7th edition) at a single institution between 2006 and 2017 was conducted. Information on the use of ARBs, ACEIs, demographics, and tumor-related factors was collected. Kaplan-Meier and Cox proportional hazard analyses were performed to assess the impact of ARBs and ACEIs combined with SBRT respectively on the treatment outcomes of these patients. Results: In total, 116 patients were included in the study, among whom 38/116 (32.76%) received ACEIs, and 20/116 (17.24%) received ARBs. In the multivariable analysis, the use of ARBs, but not ACEIs, with SBRT, was significantly associated with the increased risk of dissemination (Hazard Ratio (HR): 2.97; CI: 1.40-6.27; p < 0.004) compared to SBRT without ARBs. The tumor size of > = 3 cm was associated with significantly decreased time to local failure and OS compared to tumor size <3cm. Conclusion: In the current retrospective study, the use of ARBs, in combination with SBRT, was associated with a significantly increased risk of disease dissemination in early-stage NSCLC compared to SBRT alone. The findings warrant further investigations on the concurrent use of ARBs, ACEIs, and other medicines used for chronic diseases with SBRT for early-stage NSCLC.

Survival outcomes of stage I small cell lung cancer (SCLC) treated with stereotactic body radiation therapy (SBRT) versus external beam radiation therapy (EBRT): An NCDB analysis.

e20638 Background: Patients with stage I (T1/T2a, N0) SCLC have a 5-year survival of 48% after surgical resection. Unfortunately, 70% of limited stage patients are inoperable and thus reliant on definitive radiation. The use of SBRT has increased 16-fold from 2004-2013 with continued widespread acceptance due to its safety and projected efficacy; however, there is no category one evidence to support this practice. Currently NCCN guidelines cite experience of SBRT in 117 patients from two studies. The impact of SBRT versus EBRT with or without chemotherapy is not yet well defined and requires more evidence to influence treatment decisions. Methods: We used National Cancer Database (NCDB) to identify 4,012 patients with clinical stage I SCLC treated with surgery, or EBRT with chemotherapy, or SBRT with or without chemotherapy from 2011 to 2020. The primary outcome analyzed was overall survival (OS). Secondary analyses evaluated differences amongst age, gender, race, institution, and Charlson Comorbidity Index (CCI). Kaplan-Meier (KM) plots were used to examine survival outcomes and descriptive analysis was performed to examine the characteristics of clinical variables by the different treatment modalities. Cox regression analysis was used to identify factors associated with OS. Results: The utilization of surgery and SBRT in stage I SCLC has increased over the last fifteen years. As of 2020, SBRT volume has increased 657-fold and is combined with chemotherapy in more than 50% of cases. From 2010-2019, those who were treated with surgery-based therapy had a survival advantage (HR 0.64 95%CI 0.58-0.71, p < 0.01) compared to multimodality radiotherapy techniques. For those treated with definitive radiation, there was no significant difference between EBRT with chemotherapy and SBRT with or without chemotherapy (HR 1.11 95%CI 0.97-1.28, p = 0.135). Patients treated with SBRT alone experienced a significantly shorter median OS of 20.4 months compared to those who received SBRT with chemotherapy (median OS 34.3 months, HR 1.74 95%CI 1.38-2.20, p < 0.01). Multivariate analysis revealed better OS for patients under the age of 64 (HR 0.51 95%CI 0.44-0.58, p <0.01) and those with lower CCI (CCI 0, HR 0.82 95%CI 0.70-0.90, p< 0.01); worse OS for males (HR 1.26 95%CI 1.16-1.37, p < 0.01); and no difference between academic or non-academic institutions (HR 0.92 95%CI 0.84-1.01, p= 0.094), white versus black (HR 0.84 95%CI 0.71-1.00, p = 0.054) or non-white patients (HR 1.06 95%CI 0.75-1.50, p = 0.736). Conclusions: Our preliminary results suggest surgery-based multimodality therapy is associated with a higher survival for medically operable patients. There was no survival advantage of EBRT with chemotherapy compared to SBRT especially when chemotherapy is given. Further statistical analysis is underway to confirm these trends and survival differences.

Impact of Systemic Autoimmune Diseases on Treatment Outcomes and Radiation Toxicities in Patients with Stage I Non-Small Cell Lung Cancer Receiving Stereotactic Body Radiation Therapy: A Matched Case-Control Analysis.

We aimed to evaluate the impact of systemic autoimmune diseases (SADs) on treatment outcomes and radiation toxicities following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We queried an institution-based database on patients with SADs treated with SBRT for lung cancer between 2001 and 2016 (SAD group). Each patient was matched to three controls without SADs. The primary outcomes of interest were the overall survival (OS) and local control rate (LCR). The secondary outcomes were radiation toxicities of grades ≥2 (≥G2). Twelve patients with SADs were matched to 36 controls. The median follow-up duration was 3.6 years. There was a significant intergroup difference in the OS (hazard ratio [HR]: 4.11, 95% confidence incidence [CI]: 1.82−9.27, p < 0.001) and LCR (HR: 15.97, 95% CI: 2.89−88.29, p < 0.001). However, there were no significant intergroup differences in the odds of acute (odds ratio [OR]: 0.38, 95% CI: 0.02−8.91, p = 0.550) and late (OR: 2.20, 95% CI: 0.32−15.10, p = 0.422) ≥G2 radiation pneumonitis. No other ≥G2 toxicities were identified. In conclusion, although radiation toxicities are not enhanced by SADs, SADs are risk factors of poor prognosis following SBRT for stage I NSCLC.

Divergent Interpretations of Imaging After Stereotactic Body Radiation Therapy for Lung Cancer

PurposeConflicting information from health care providers contributes to anxiety among cancer patients. The purpose of this study was to investigate discordant interpretations of follow-up imaging studies after lung stereotactic body radiation therapy (SBRT) between radiologists and radiation oncologists. Methods and MaterialsPatients treated with SBRT for stage I non-small cell lung cancer from 2007 to 2018 at Duke University Medical Center were included. Radiology interpretations of follow-up computed tomography (CT) chest or positron emission tomography (PET)/CT scans and the corresponding radiation oncology interpretations in follow-up notes from the medical record were assessed. Based on language used, interpretations were scored as concerning for progression (Progression), neutral differential listed (Neutral Differential), or favor stability/postradiation changes (Stable). Neutral Differential required that malignancy was specifically listed as a possibility in the differential. Encounters were categorized as discordant when either radiology or radiation oncology interpreted the surveillance imaging as Progression when the other interpreted the imaging study as Stable or Neutral Differential. The incidence of discordant interpretations was the primary endpoint of the study. ResultsFrom 2007 to 2018, 139 patients were treated with SBRT and had available follow-up CT or PET-CT imaging for the analysis. Median follow-up was 61 months and the median number of follow-up encounters per patient was 3. Of 534 encounters evaluated, 25 (4.7%) had overtly discordant interpretations of imaging studies. This most commonly arose when radiology felt the imaging study showed Progression but radiation oncology favored Stable or Neutral Differential (24/25, 96%). No patient or treatment variables were found to be significantly associated with discordant interpretations on univariate analysis including type of scan (CT 22/489, 4.5%; PET-CT 3/45, 7%; P = .46). ConclusionsSurveillance imaging after lung SBRT is often interpreted differently by radiologists and radiation oncologists, but overt discordance was relatively low at our institution. Providers should be aware of differences in interpretation patterns that may contribute to increased patient distress.

MA03.09 Real-World Acute Toxicity and 90-day Mortality in Patients with Stage I Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiotherapy.

Stereotactic body radiotherapy (SBRT) has firmly established its role in the management of stage I non-small cell lung cancer (NSCLC). Results from trials are difficult to generalize to the entire patient population in the real world. In addition, in contrast to trials, real-world data provides increased statistical power to study rare outcomes and their predictors. The primary aim of this nationwide study was to determine the real-world incidence of acute toxicity and 90-day mortality in patients treated with SBRT for stage I NSCLC.

Stereotactic Body Radiotherapy for Stage I Lung Cancer With a New Real-time Tumor Tracking System.

Suppression of respiratory movement is crucial for safe and effective stereotactic body radiotherapy (SBRT). SyncTraX FX4 is a novel device for synchronous respiratory irradiation. The purpose of this study was to evaluate the efficacy and toxicity of SBRT using SyncTraX FX4 for patients with lung cancer. Patients treated with SBRT using SyncTraX FX4 between November 2017 and August 2020 were included. In all cases, fiducial markers were inserted into the lung, and the total dose administered was 55 or 60 Gy, depending on the distance from the central region of the lung. Acute and late toxicities were reported, and local control, progression-free survival, cancer-specific survival, and overall survival were analyzed. We evaluated 16 patients and 17 sites. The median follow-up period was 14.4 months. In both the acute and late phases, one patient experienced grade 3 radiation pneumonitis; however, grade 4 or higher toxicities were not observed. There was no local recurrence during the observation period, and the overall survival, cancer-specific survival, and progression-free survival at 2 years were 54.6%, 85.1%, and 33.7%, respectively. SBRT with SyncTraX FX4 can provide safe and effective treatment for lung cancer patients in poor condition.

Microwave Ablation versus Stereotactic Body Radiotherapy for Stage I Non–Small Cell Lung Cancer: A Cost-Effectiveness Analysis

PurposeTo assess the cost effectiveness of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) for patients with inoperable stage I non–small cell lung cancer (NSCLC). Materials and MethodsA literature search was performed in MEDLINE with broad search clusters. A decision-analytic model was constructed over a 5-year period. The model incorporated treatment-related complications and long-term recurrence. All clinical parameters were derived from the literature with preference to long-term prospective trials. A healthcare payers’ perspective was adopted. Outcomes were measured in quality-adjusted life years (QALYs) extracted from prior studies and U.S. dollars from Medicare reimbursements and prior studies. Base case calculations, probabilistic sensitivity analysis with 10,000 Monte Carlo simulations, and multiple 1- and 2-way sensitivity analyses were performed. ResultsMWA yielded a health benefit of 2.31 QALYs at a cost of $195,331, whereas SBRT yielded a health benefit of 2.33 QALYs at a cost of $225,271. The incremental cost-effectiveness ratio was $1,480,597/QALY, indicating that MWA is the more cost-effective strategy. The conclusion remains unchanged in probabilistic sensitivity analysis with MWA being the optimal cost strategy in 99.84% simulations. One-way sensitivity analyses revealed that MWA remains cost effective when its annual recurrence risk is <18.4% averaged over 5 years, when the SBRT annual recurrence risk is >1.44% averaged over 5 years, or when MWA is at least $7,500 cheaper than SBRT. ConclusionsMWA appears to be more cost effective than SBRT for patients with inoperable stage I NSCLC.

Effectiveness of Thermal Ablation and Stereotactic Radiotherapy Based on Stage I Lung Cancer Histology

PurposeTo assess whether the effectiveness of thermal ablation (TA) and stereotactic body radiotherapy (SBRT) as initial treatments for stage I lung cancer varies depending on the histological subtype. Materials and MethodsThe 2004–2016 National Cancer Database was queried for patients with American Joint Committee on Cancer stage I lung cancer treated with TA or SBRT. Patients <18 years, those treated with surgery or chemotherapy, or those with unknown survival and follow-up were excluded. TA and SBRT patients were 1:5 propensity score matched separately for each histological subtype to adjust for confounders. Overall survival (OS) was assessed using Cox models. ResultsA total of 28,425 patients were included (SBRT, n = 27,478; TA, n = 947). TA was more likely to be used in Caucasian patients, those with more comorbidities and smaller neuroendocrine tumors (NETs) of the lower lobe, and those whose treatment had taken place in the northeastern United States. After propensity score matching, a cohort with 4,085 SBRT and 817 TA patients with balanced confounders was obtained. In this cohort, OS for TA and SBRT was comparable (hazard ratio = 1.07; 95% confidence interval,0.98–1.18; P = .13), although it varied by histological subtypes: higher OS for TA was observed in patients with non–small cell NETs (vs SBRT hazard ratio = 0.48; 95% confidence interval, 0.24–0.95; P = .04). No significant OS differences between TA and SBRT were noted for adenocarcinomas, squamous cell carcinomas, small cell carcinomas, and non-neuroendocrine large cell carcinomas (each, P > .1). ConclusionsOS following TA and SBRT for stage I lung cancer is comparable for most histological subtypes, except that OS is longer after TA in non–small cell NETs.

Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline.

The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy (RT) for small-cell lung cancer (SCLC). Because of the relevance of this topic to ASCO membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. The ASTRO guideline on RT for SCLC was reviewed for developmental rigor by methodologists. Then, an ASCO Expert Panel reviewed the content and the recommendations. The ASCO Expert Panel determined that the recommendations from ASTRO guideline on RT for SCLC, published in June 2020, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed ASTRO guideline on RT for SCLC with a few discussion points. Recommendations addressed thoracic radiotherapy for limited-stage SCLC, role of stereotactic body radiotherapy in stage I or II node-negative SCLC, prophylactic cranial radiotherapy, and thoracic consolidation for extensive-stage SCLC.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Systematic review of stereotactic body radiotherapy in stage III non-small cell lung cancer.

Despite adequate treatment, 50% of stage III locally advanced inoperable non-small cell lung cancer (NSCLC) patients have a locoregional relapse. Local control on early stages on the contrary, is as high as 85–90% with stereotactic body radiotherapy (SBRT). The addition of SBRT to conventional chemoradiation or its use in monotherapy in stage III NSCLC is a novel strategy to decrease local failure that has been explored by various authors. This is a systematic review of studies using SBRT in inoperable stage III NSCLC. Search results obtained 141 articles of which only 6 original studies were pointed as relevant. Three of these studies were prospective, of which 2 were phase I dose-scalation studies and remaining 3 were retrospective. In summary, SBRT outcomes on 134 patients were included. Median dose in the SBRT treatment was 22.5 Gy in 2 to 7 fractions. Obtained global toxicity was 3.7% grade 5 and 14.17% grade 3. Dose-escalation studies proposed a 2 fraction SBRT schedule of 20–24 Gy, obtaining a 78% local control rate at 1 year and an OS of 67%. Initial improvement in local control with this innovative therapeutic strategy has led to ongoing phase II and III clinical trials that will evaluate the efficiency of SBRT in stage III NSCLC clinical scenario.

Thermal ablation versus stereotactic body radiotherapy for stage I non-small cell lung cancer: A cost-effectiveness analysis.

e21061 Background: Stereotactic body radiotherapy (SBRT) and thermal ablation are increasingly used to treat medically inoperable patients with non-small cell lung cancer (NSCLC). The purpose of this study is to assess the cost-effectiveness of microwave (MWA) and stereotactic body radiotherapy (SBRT) for patients with stage I NSCLC. Methods: A decision-analysis model was constructed over a 5-year of Medicare billing data from a health care sector’s perspective using TreeAge Pro Suite 2019 (TreeAge Software LLC, Cambridge, MA). The two evaluated strategies were SBRT and MWA. All clinical, cost and health utility parameters were derived from the literature with preference to long-term prospective trials and assigned appropriate statistical distributions. Costs and health utilities (quantified by quality-adjusted life years (QALY)) associated with procedure, short-term complications, long-term surveillance and disease progression were incorporated. A willingness-to-pay (WTP) threshold of $100,000/QALY was used. One QALY is equivalent to 1 year of life in perfect health. Strategies were compared using incremental cost-effectiveness ratio (ICER). Base case calculations, Monte Carlo Simulations with 10,000 iterations drawing parameters from their respective distributions, and multiple sensitivity analyses were performed. Results: Literature review and interpolation showed that average annual recurrence risk of SBRT and MWA were 4.64% and 10.4% respectively. SBRT yielded 2.33 QALY and MWA yielded 2.31 QALY. The difference in health benefit is equivalent to 1 week of life in perfect health. The overall costs were $225,271 and $195,331. The ICER of MWA in reference to SBRT was $1,480,597/QALY, which is more than 10 times of the WTP threshold currently used in the US, indicating that MWA is the more cost-effective strategy. MWA was the optimal strategy in 99.84% of the Monte Carlo simulations. One-way sensitivity analyses showed that MWA is more cost-effective than SBRT if recurrence risk of MWA is &lt; 18.4% per year or recurrence risk of SBRT is &gt; 1.44% per year, or cost of MWA is lower than or at most $7,500 more than SBRT. One-way sensitivity analysis showed that MWA would achieve a higher health benefit than SBRT if the overall survival after MWA was &gt; 76.9% per year or after SBRT was &lt; 75.6% per year. Conclusions: Our study showed that MWA is more cost-effective than SBRT for medically inoperable stage I NSCLC patients with comparable health benefits based on multiple robust probabilistic and deterministic sensitivity analyses.

Stereotactic Body Radiotherapy for Stage I Renal Cell Carcinoma: More Research Required

Stereotactic Body Radiotherapy for Stage I Renal Cell Carcinoma: More Research Required

Stereotactic Body Radiotherapy for Stage I Renal Cell Carcinoma: National Treatment Trends and Outcomes Compared to Partial Nephrectomy and Thermal Ablation

PurposeTo assess use of stereotactic body radiotherapy (SBRT) for stage I renal cell carcinoma (RCC) and compare outcomes with thermal ablation and partial nephrectomy (PN). Materials and MethodsThe 2004–2015 National Cancer Database was investigated for histopathologically proven stage I RCC treated with PN, cryoablation, radiofrequency (RF) or microwave (MW) ablation, or SBRT. Patients were propensity score–matched to account for potential confounders, including patient age, sex, race, comorbidities, tumor size, histology, grade, tumor sequence, administration of systemic therapy, treatment in academic vs nonacademic centers, treatment location, and year of diagnosis. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models. ResultsA total of 91,965 patients were identified (SBRT, n = 174; PN, n = 82,913; cryoablation, n = 5,446; RF/MW ablation, n = 3,432). Stage I patients who received SBRT tended to be older women with few comorbidities treated at nonacademic centers in New England states. After propensity score matching, a cohort of 636 patients was obtained with well-balanced confounders between treatment groups. In the matched cohort, OS after SBRT was inferior to OS after PN and thermal ablation (PN vs SBRT, hazard ratio [HR] = 0.29, 95% confidence interval [CI] 0.19–0.46, P < .001; cryoablation vs SBRT, HR = 0.40, 95% CI 0.26–0.60, P < .001; RF/MW ablation vs SBRT, HR = 0.46, 95% CI 0.31–0.67, P < .001). Compared with PN, neither cryoablation nor RF/MW ablation showed significant difference in OS (cryoablation vs PN, HR = 1.35, 95% CI 0.80–2.28, P = .258; RF/MW ablation vs PN, HR = 0.64, 95% CI 0.95–2.55, P = .079). ConclusionsCurrent SBRT protocols show lower OS compared with thermal ablation and PN, whereas thermal ablation and PN demonstrate comparable outcomes.

Individualized Prediction of Early Post-Treatment Mortality Risk in Stage I Non-Small Cell Lung Cancer: A Machine Learning-Based Approach

In stage I non-small cell lung cancer (NSCLC), the STARS/ROSEL pooled analysis showed worse overall survival (OS) but equivalent cancer-specific survival with surgical resection compared to stereotactic body radiation therapy (SBRT), with other studies demonstrating interaction effects between early post-treatment mortality and age. Therefore, appropriate patient selection is essential to optimize survival outcomes. We utilize predictive modeling using machine learning (ML) of mortality risk at 90 days post-treatment in stage I NSCLC patients. Patients with T1-T2aN0M0 NSCLC, diagnosed from 2004 to 2015, were identified using the National Cancer Database and divided into separate surgery and SBRT cohorts. All patients were censored 90 days after receipt of definitive treatment. Training and validation sets were formed by a randomized 80%/20% split. Features (age, histology, tumor size, and comorbidity score) were pre-specified based on predictors of post-treatment mortality identified in literature. Three different ML approaches were tested: 1) a Cox proportional hazards (CPH) linear model, 2) a survival Support Vector Machine (SVM) model, and 3) a gradient-boosted regression tree (GBRT) model using Cox proportional hazard loss. Hyperparameter tuning was performed manually using grid search techniques. Model performance was evaluated using Harrell’s concordance index (CI). Feature importance and interaction effects were modeled using Shapley additive explanations (SHAP) values applied to the GBRT model. The open-source scikit-survival library in Python 3.7 was used for all analyses. We identified 118,087 stage I NSCLC patients (81.0%) receiving surgery and 27,659 receiving SBRT (19.0%). Within the surgery cohort, the GBRT model had the best performance (CI=0.689), as compared to the SVM model (0.673) and CPH model (0.672). Within the SBRT cohort, similarly, the GBRT model performed the best (CI=0.591) compared to the SVM model (CI=0.572) and CPH model (0.570). Based on feature importance rankings, age had the highest importance in both the surgery and SBRT cohorts. When using SHAP values to model nonlinear interaction effects between age and treatment received, an inflection point was identified between age 73 and 74, indicating GBRT model predictions of generally greater 90-day post-treatment mortality with SBRT in patients age 18-73 and greater risk with surgery in patients age 74+. We describe a ML-based approach for analyzing comparative 90-day post-treatment mortality risk between surgery and SBRT in stage I NSCLC. We found an inflection point in the interaction between age and treatment modality, underscoring the need for patient selection when assessing treatment options. Our findings may aid individualized decision-making in early stage NSCLC.

Dose Discrepancy between the Gross Tumor Volume and the Planning Target Volume By Surrounding Density in Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

Dose Discrepancy between the Gross Tumor Volume and the Planning Target Volume By Surrounding Density in Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

AB003. Stereotactic body radiation therapy vs. pulmonary resection

: Pulmonary resection remains the accepted standard of care for early stage non-small cell lung cancer (NSCLC) in patients with adequate cardiopulmonary reserve. Radiation therapy, and in particular stereotactic body radiation therapy (SBRT), has traditionally been recommended as curative therapy for medically unfit patients who harbor early stage lung cancer. As a consequence of the rising success of SBRT in patients with medically inoperable early stage NSCLC (evidenced by Radiation Therapy Oncology Group trials 0236 and 0915), there has been keen interest in exploring this modality in operable patients. SBRT to lung is often very well tolerated, thus making it very attractive to patients. The risk of series complications in carefully selected patients is low. Equipoise among surgeons and the medical community for the use of SBRT as curative therapy for patients eligible for surgery has been limited, thus contributing to the poor accrual and early closure of 3 randomized trials attempting to directly compare SBRT to surgery in operable patients. These trials included the STARS trial (Study of Anastrozole and Radiotherapy Sequencing), the ROSEL trial [Either Surgery or Stereotactic Radiotherapy for Early-Stage (IA) Lung Cancer] and the American College of Surgeons Oncology Group (ACOSOG) Z4099 trial. No preliminary data is available from the ACOSOG trial. The STARS and ROSEL trial randomized operable patients with tumors <4 cm (cT1–T2a) and required invasive mediastinal staging in patients harboring radiographically suspicious lymph nodes. Sublobar resection was not permitted in these trials. Since patient accrual was limited (n=58 total patients) the two trials were combined in a controversial publication that showed improved overall survival and decreased toxicity with SBRT compared to surgery. This has spawned additional randomized trials including the STABLE-MATES trial comparing sublobar resection and SBRT in patients with stage I NSCLC (NCT02468024) with an estimated enrollment of 258 patients, a Veterans Affairs Lung Cancer or Stereotactic Radiotherapy (VALOR) trial (NCT02984761) with estimated enrollment of 670 patients, and lastly, a phase II United Kingdom sponsored SABRTooth study (NCT02629458) that is enrolling up to 54 patients. The lack of randomized data has stimulated multiple publications that retrospectively examine these modalities in single center case series and more recently in larger data sets derived from the National Cancer Database (NCDB), the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database and the United States Veterans Affairs Health Care System. These retrospective analyses are clearly limited by patient selection bias and different levels of staging accuracy. Propensity matched retrospective series showed that overall survival was no different at 1 year but favored surgery at 3 years. Cancer-specific survival (clearly a better outcome measure particularly in elderly patients receiving SBRT) was no different compared to surgery, nor was local failure, or the risk of developing distant metastases. Collectively, the studies that used large data with statistical matching demonstrated a survival advantage of surgery (namely lobectomy) over SBRT for stage I NSCLC but raised awareness of the increased post procedure morbidity and mortality for surgery compared to SBRT. Interestingly, sublobar resection versus SBRT in these large data sets had mixed results with some showing survival improvement with surgery and some showing no survival difference. Surgery appears superior at later time points. In a phase II ablate and resect human clinical trial (MISSILE-NSCLC, NCT02136355) for early stage (T1–T2) NSCLC, 35 patients underwent neoadjuvant SBRT using 54–60 Gy in 3–8 fractions followed by surgery at an interval of 10 weeks. The authors reported a 60% pathologic complete response rate, invoking many questions about local control of SBRT. Assessment of local control after SBRT remains the single most challenging real-world clinical problem. The lung injury post ablation is heterogenous and requires very careful observation with imaging modalities that lack sensitivity and specificity for recurrence. At present, the American Society of Radiation Oncology does not recommend SBRT for operable patients with early stage NSCLC outside of a clinical trial.

Patient-reported Outcomes After the Treatment of Early Stage Non–small-cell Lung Cancer With Stereotactic Body Radiotherapy Compared With Surgery

IntroductionAs there is increasing evidence for comparable survival after either stereotactic body radiotherapy (SBRT) or surgery for patients with stage I non–small-cell lung cancer (NSCLC), treatment impact on the quality of life (QoL) is essential for well-informed decision-making. Our previous work evaluated health utility between surgery and SBRT in stage I NSCLC. The aim of this secondary analysis is to directly compare QoL in the first year after SBRT and surgery. Materials and MethodsQoL was assessed at baseline and 3, 6, and 12 months after treatment. Two prospectively collected databases of patients with clinically proven stage I NSCLC, from 2 large hospitals in the Netherlands, were pooled (n = 306; 265 patients were treated with SBRT and 41 patients with surgery). To correct for confounding, propensity scores were calculated, to be selected for surgical treatment. A mixed model analysis was used to study differences in QoL between the 2 treatments. ResultsThe 41 surgical patients were matched to 41 SBRT patients on propensity score with a 1:1 ratio. At baseline, patients in the surgery group report a lower QoL compared with patients in the SBRT group. However, during the first year after treatment, no clinical meaningful differences were observed, except for role functioning, between patients treated using either modality. ConclusionThis study comparing a matched cohort revealed no clinically significant differences in QoL following either SBRT or surgery for early stage NSCLC. These results support the hypothesis that surgery and SBRT are comparable treatments.

Local Control After Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer

Numerous dose and fractionation schedules have been used to treat medically inoperable stage I non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy. We evaluated published experiences with SBRT to determine local control (LC) rates as a function of SBRT dose. One hundred sixty published articles reporting LC rates after SBRT for stage I NSCLC were identified. Quality of the series was assessed by evaluating the number of patients in the study, homogeneity of the dose regimen, length of follow-up time, and reporting of LC. Clinical data including 1, 2, 3, and 5-year tumor control probabilities for stages T1, T2, and combined T1 and T2 as a function of the biological effective dose were fitted to the linear quadratic, universal survival curve, and regrowth models. Forty-six studies met inclusion criteria. As measured by the goodness of fit χ2/ndf, with ndf as the number of degrees of freedom, none of the models were ideal fits for the data. Of the 3 models, the regrowth model provides the best fit to the clinical data. For the regrowth model, the fitting yielded an α-to-β ratio of approximately 25Gy for T1 tumors, 19Gy for T2 tumors, and 21Gy for T1 and T2 combined. To achieve the maximal LC rate, the predicted physical dose schemes when prescribed at the periphery of the planning target volume are 43±1Gy in 3 fractions, 47±1Gy in 4 fractions, and 50±1Gy in 5 fractions for combined T1 and T2 tumors. Early-stage NSCLC is radioresponsive when treated with SBRT or stereotactic ablative radiation therapy. A steep dose-response relationship exists with high rates of durable LC when physical doses of 43-50Gy are delivered in 3 to 5 fractions.

Stereotactic body radiotherapy for lung cancer in patients with interstitial lung disease

Stereotactic body radiotherapy (SBRT) is a highly dose-concentrated radiotherapy that can spare damage to normal organs much more than conventional radiotherapy. Severe radiation pneumonitis (RP) after stereotactic SBRT for thoracic lesions is rare but sometimes gets severe. In this review, we presented the reported frequency of severe RP after SBRT for stage I NSCLC, its risk factors, and the attempts at clarifying individual predictive risk factors. The ratio of fatal RP after SBRT for lung tumor in patients with accompanying pulmonary interstitial changes is more than 5%, and overall survival is poor. The dose to the normal lung and interstitial changes in the background lung are important predictive factors of severe RP, with idiopathic pulmonary fibrosis (IPF) being the biggest risk factor for severe RP, but these interstitial lung diseases (ILDs) are not always a contraindication for thoracic SBRT. Based on the high fatality rate, it would be reasonable to avoid prompt SBRT by watchful waiting in cases of indolent or non-aggressive tumors, such as ground-glass tumors. It would be better to use or recommend more highly precise irradiation systems or particle therapy (PT) that can reduce radiation doses to the normal lung more, in particular for the cases with IPF. Identification of biomarkers indicating an individual’s risk level for severe RP, such as single nucleotide polymorphisms (SNPs), would be important in treatment decisions, but it needs further research. Though there are no reliable drugs for treating severe RP, anti-fibrotic agents, such as pirfenidone, might be effective in its prevention or alleviation.