G. Marwaha

Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer Tumors Greater Than 5 cm: Safety and Efficacy

PURPOSE The purpose of this study was to determine outcomes of patients with node-negative medically inoperable non-small cell lung cancer (NSCLC) whose primary tumors exceeded 5 cm and were treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS We surveyed our institutional prospective lung SBRT registry to identify treated patients with tumors >5 cm. Treatment outcomes for local control (LC), locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were assessed by Kaplan-Meier estimates. Toxicities were graded according to Common Terminology Criteria for Adverse Events version 4. Mean pretreatment pulmonary function test values were compared to mean posttreatment values. RESULTS From December 2003 to July 2014, 40 patients met study criteria. Median follow-up was 10.8 months (range: 0.4-70.3 months). Median age was 76 years (range: 56-90 years), median body mass index was 24.3 (range: 17.7-37.2), median Karnofsky performance score was 80 (range: 60-90), and median Charlson comorbidity index score was 2 (range: 0-5). Median forced expiratory volume in 1 second (FEV1) was 1.41 L (range: 0.47-3.67 L), and median diffusion capacity (DLCO) was 47% of predicted (range: 29%-80%). All patients were staged by fluorodeoxyglucose-positron emission tomography/computed tomography staging, and 47.5% underwent mediastinal staging by endobronchial ultrasonography. Median tumor size was 5.6 cm (range: 5.1-10 cm), median SBRT dose was 50 Gy (range: 30-60 Gy) in 5 fractions (range: 3-10 fractions). Eighteen-month LC, LRC, DFS, and OS rates were 91.2%, 64.4%, 34.6%, and 59.7%, respectively. Distant failure was the predominant pattern of failure (32.5%). Three patients (7.5%) experienced grade 3 or higher toxicity. Mean posttreatment FEV1 was not significantly reduced (P=.51), but a statistically significant absolute 6.5% (P=.03) reduction in DLCO was observed. CONCLUSIONS Lung SBRT for medically inoperable node-negative NSCLC with primary tumors larger than 5 cm is safe and provides excellent local control with limited toxicity. The predominant pattern of failure in this population was distant failure.

Lung Stereotactic Body Radiation Therapy: Regional Nodal Failure Is Not Predicted by Tumor Size

Introduction: To examine regional nodal failure patterns with respect to lesion size in medically inoperable early-stage non–small cell lung cancer (NSCLC) patients treated with definitive lung stereotactic body radiation therapy (SBRT). Methods: Between 2004 and 2012, 342 medically inoperable early-stage NSCLC patients treated with definitive SBRT were identified in our institutional review board–approved prospective registry. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance. Kaplan–Meier analysis was performed with the log-rank test used to detect differences between lesion size and nodal failure patterns. Cox-proportional hazard regression analysis was performed to identify predictors of nodal failure. Results: Median follow-up was 17.6 months (range, 0–84 months). Median tumor size, positron emission tomography maximum standardized uptake value, and dose/fractionation were 2.2 cm (range, 0.8–7.2 cm), 6.7 (range, 1–59), and 50 Gray (Gy)/five fractions, respectively. Of the 342 lesions evaluated, 14.6% (50 of 342) experienced nodal failure. Nodal failure rates were 17.45% (26 of 149), 10.3% (11 of 107), 14.1% (10 of 71), and 20% (3 of 15) for lesions less than or equal to 2 cm, 2.1 to 3 cm, 3.1 to 5 cm, and greater than 5 cm, respectively. Rates of nodal failure were not significantly different between the four different size groups (p = 0.15). On univariate analysis, 2.1 to 3 cm lesions versus less than or equal to 2 cm exhibited less nodal failure after SBRT (hazard ratio = 0.406; 95% confidence interval = 0.189–0.87; p = 0.0205). No other patient, tumor, or treatment factor significantly affected nodal failure. Conclusion: For early-stage NSCLC treated with SBRT, tumor size does not influence the rates of regional nodal failure. This finding warrants further investigation on the possible mechanisms of SBRT by which loco-regional control is improved.

Isolated Nodal Failure after Stereotactic Body Radiotherapy for Lung Cancer: The Role for Salvage Mediastinal Radiotherapy

Introduction: Isolated nodal failure (INF) without synchronous local or distant failure is an uncommon occurrence after stereotactic body radiation therapy (SBRT) for lung cancer. Here we review the natural history and patterns of failure after post‐SBRT INF with or without salvage mediastinal radiotherapy (SvRT). Methods: Patients treated with SBRT for non–small cell lung cancer with definitive intent were identified. Patients who experienced hilar or mediastinal INF without synchronous distant, lobar, or local failure were included and grouped according to the use of SvRT. The rates of subsequent locoregional control, distant metastases, progression‐free survival (PFS), and overall survival were assessed. Results: Of 797 patients treated with definitive SBRT, 24 (3%) experienced INF and 15 (63%) received SvRT. The most common SvRT regimen (53%) was 45 Gy in 15 fractions. The median follow‐up after INF was 11.3 months for survivors. There were no grade 3 or higher toxicities after SvRT. The 1‐year Kaplan‐Meier PFS and overall survival estimates were 33% and 56% for patients not receiving radiotherapy and 75% and 73% with SvRT. After SvRT, the rate of locoregional control at 1 year was 84.4%. Crude rates of distant failure were 20.0% with SvRT and 22.2% with no radiotherapy. Of the 13 deaths observed, five (38%) were related to distant progression of lung cancer, four (31%) to comorbidities, three (23%) to mediastinal progression, and one (8%) to an unknown cause. Conclusions: INF is uncommon after SBRT. Despite the significant comorbidities of this population, intrathoracic progression remains a contributor to morbidity and mortality. SVRT for INF is well tolerated and may improve PFS.

Dosimetric Benefit of a New Ophthalmic Radiation Plaque

PURPOSE To determine whether the computed dosimetry of a new ophthalmic plaque, EP917, when compared with the standard Collaborative Ocular Melanoma Study (COMS) plaques, could reduce radiation exposure to vision critical structures of the eye. METHODS AND MATERIALS One hundred consecutive patients with uveal melanoma treated with COMS radiation plaques between 2007 and 2010 were included in this study. These treatment plans were generated with the use of Bebig Plaque Simulator treatment-planning software, both for COMS plaques and for EP917 plaques using I-125. Dose distributions were calculated for a prescription of 85 Gy to the tumor apex. Doses to the optic disc, opposite retina, lens, and macula were obtained, and differences between the 2 groups were analyzed by standard parametric methods. RESULTS When compared with the COMS plaques, the EP917 plaques used fewer radiation seeds by an average difference of 1.94 (P<.001; 95% confidence interval [CI], -2.8 to -1.06) and required less total strength of radiation sources by an average of 17.74 U (air kerma units) (P<.001; 95% CI, -20.16 to -15.32). The total radiation doses delivered to the optic disc, opposite retina, and macula were significantly less by 4.57 Gy, 0.50 Gy, and 11.18 Gy, respectively, with the EP917 plaques vs the COMS plaques. CONCLUSION EP917 plaques deliver less overall radiation exposure to critical vision structures than COMS treatment plaques while still delivering the same total therapeutic dose to the tumor.

Lung stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer in the very elderly (≥80 years old): Extremely safe and effective

OBJECTIVE Stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) is the standard of care in medically inoperable patients. In very elderly patients, previous studies have shown SBRT to offer excellent local control, though with higher toxicities than in younger populations. We report our institutional experience using SBRT in the definitive management of NSCLC in patients ≥80years old. MATERIALS AND METHODS Using an IRB-approved registry of 158 patients treated with definitive-intent lung SBRT for early-stage NSCLC at our institution between 2010 and 2016, 31 consecutively treated patients ≥80years of age were identified. CTCAEv4 scales were prospectively recorded during follow-ups and utilized for toxicity assessments. Kaplan-Meier estimates were utilized for survival analyses. RESULTS For the 31 patients (with 34 lesions) included, median age was 83 (R: 80-93), median ECOG performance status was 2 (R: 0-3), and median follow-up was 15.8months (R: 3.1-48.3). Median PTV size was 24.0cm3 (R: 5.83-62.1cm3). Median prescription dose was 54Gy in 3 fractions (R: 50-60Gy in 3-8 fractions). Local control was 100% at 1year and 92.3% at 2years. Median survival was 29.1months. There were no grade 2-5 toxicities. Grade 1 toxicities included: fatigue in 5 patients (16.1%), asymptomatic (radiographic) pneumonitis in 12 (38.7%), and dyspnea in 2 (6.5%). CONCLUSIONS Lung SBRT with a BED of ≥100Gy10 for very elderly patients with NSCLC is extremely safe and effective, with inordinately low toxicity rates (zero grade 2-5 toxicities). With stringent dosimetric parameters and planning guidelines, patients ≥80years remain excellent candidates for full-dose SBRT. SUMMARY SBRT for early-stage NSCLC is the accepted standard of care in medically inoperable patients, though in many very elderly patients, dose is either de-intensified or withheld for concern of toxicity in the setting of advanced age and competing risks. In this study of our very elderly (≥80years old) early-stage NSCLC patients, we highlight both the extremely high efficacy and tolerability (zero grade 2 or above toxicities) associated with definitive intent SBRT.

Radiation Therapy: Orbital Tumors

Orbital tumors are rare overall, comprising 0.1% of all tumors and less than 20% of all orbital diseases. Tumors may be benign, locally aggressive, or malignant. Of the malignant tumors, lymphomas and metastases are the most common and are primarily seen in the elderly population. While surgery and chemotherapeutic agents are often employed in the management of these lesions, not all patients are candidates for these therapies. Radiation therapy offers a noninvasive, well-tolerated primary treatment modality, whereby vision-sparing is feasible in many cases. In this chapter, we review an array of non-neoplastic entities and orbital tumors, for which there exists a role for radiation, and the radiotherapeutic techniques and applications in their management.

Progress in the Treatment and Outcomes for Early-Stage Non-Small Cell Lung Cancer

PurposeThe purpose of this study is to assess temporal trends in population-based treatment and survival rates in patients with early-stage non-small cell lung cancer (NSCLC).MethodsData were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test, Kaplan–Meier method, and Cox regression models were employed in SPSS 23.0.ResultsFifty-seven thousand and eighty-eight NSCLC patients with early-stage disease from 1988 to 2014 were identified. 6409 (11.2%) were diagnosed in 1988–1994, 5800 (10.2%) 1995–1999, 13,031 (22.8%) 2000–2004, 15,786 (27.7%) 2005–2009, and 16,062 (28.1%) 2010–2014. We observed a significant increase in the proportion of older patients, adenocarcinoma histology, and rate of wedge resection over the study period. The five-year overall survival (OS) for the entire cohort was 63.3%. Those undergoing resection without adjuvant therapy had the highest outcomes. Lobectomy was associated with better outcomes compared to wedge resection or pneumonectomy. A significant difference in five-year OS by year of diagnosis (1988–1994: 58.8% vs. 1995–1999: 60.6% vs. 2000–2004: 63.2% vs. 2005–2009: 66.1%; p < 0.001) was observed. This significant OS difference was also observed regardless of age, surgery type, and T stage, but also only in those with adenocarcinoma. On multivariable analysis, year of diagnosis, age, gender, race, treatment and surgery type, histology, T stage, and tumor grade remained independent prognostic factors for OS.ConclusionsOverall survival for early-stage NSCLC has significantly improved over the recent decades despite an increasing proportion of older patients and those undergoing sublobar resection or SBRT. This finding may be limited to those with adenocarcinoma.

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery

IntroductionNeutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocyte-predominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain metastases (BM).MethodsBM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan–Meier method and cumulative incidence with competing risk for death, respectively.Results188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR > 6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. > 6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR > 6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03–2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30–2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes.ConclusionPost-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.

External Validation of the New International Association for the Study of Lung Cancer Tumor, Node, and Metastasis 8th Edition Staging System and Updated T Descriptors in Determining Prognosis for Patients With Non–Small Cell Lung Cancer Patients With N3 Disease

Objective The objective of this study is to externally validate the 8th Edition of the Tumor, Node, and Metastasis staging system and its updated T descriptors in patients with non–small cell lung cancer with N3 disease. Methods Data were extracted from the Surveillance, Epidemiology, and End Results database. Chi‐square test, Kaplan–Meier method, and Cox regression models were used in SPSS 23.0 (IBM Corp, Armonk, NY). Results A total of 7732 patients with non–small cell lung cancer with T1‐4N3M0 disease from 1988 to 2013 were identified. A total of 1410 patients (18.2%) had T1N3 disease, 2491 patients (32.2%) had T2N3 disease, 1563 patients (20.2%) had T3N3 disease, and 2268 patients (29.3%) had T4N3 disease. The 5‐year overall survival (OS) for the entire cohort was 8.4%. There was a significant difference in OS concerning T stage (T1N3: 10.8% vs. T2N3: 8.3% vs. T3N3: 8.1% vs. T4N3: 7.3%; P < .001). When stratified by the median age of patients (66 years), a significant difference in OS by stage of disease (IIIB vs. IIIC) was still observed in both the younger (P < .001) and older (P < .001) patient populations. A significant difference in disease‐specific survival (DSS) was observed by T stage (T1N3: 14.7% vs. T2N3: 11.6% vs. T3N3: 11.3% vs. T4N3: 9.7%; P < .001). On multivariate analysis, T stage, year of diagnosis, age, gender, histology, and receipt of radiotherapy remained independent prognostic factors for both OS and DSS. Conclusions The 8th Edition of the Tumor, Node, and Metastasis staging system significantly stratifies both overall and DSS between stages IIIB and IIIC among those with N3 disease. However, small absolute differences in 5‐year outcomes between T stage may suggest limited clinical relevance. Micro‐Abstract The objective of this study is to externally validate the 8th Edition Tumor, Node, and Metastasis staging system and its updated T descriptors in patients with non–small cell lung cancer with N3 disease. Our analysis suggests that the new staging system statistically stratifies outcomes between stages IIIB and IIIC in those with N3 disease. However, small absolute differences in 5‐year outcomes between T stage perhaps suggest limited clinical relevance.