Management of Malignant Pleural Mesothelioma in the Elderly Population.

BACKGROUND: The median age at diagnosis for malignant pleural mesothelioma (MPM) is approximately 72 years. Elderly patients pose unique management challenges because of the increased risk of therapy-related toxicities and mortality. Because there are no high-volume retrospective studies, prospective trials, or dedicated treatment recommendations for this population, this investigation addresses a major knowledge gap by examining national practice patterns and postoperative/survival outcomes in elderly MPM patients. METHODS: The National Cancer Database was queried for patients aged ≥ 80 years with newly diagnosed nonmetastatic MPM. Multivariable logistic regression ascertained factors associated with observation and surgery. Kaplan-Meier analysis assessed overall survival (OS), and multivariable Cox proportional hazards modeling examined factors associated with OS. Survival was also calculated following propensity matching. Additionally, postoperative outcomes were evaluated in surgical patients. RESULTS: Of 4526 patients, 2% received surgery and chemotherapy, 22% underwent chemotherapy alone, and 63% were observed. Respective median OS was 12.2, 9.5, and 4.1 months (p < 0.001). Differences between all groups persisted following propensity matching (all comparisons p < 0.05). For the 8% of patients who underwent specified definitive surgery (95% of whom received pleurectomy/decortication), 30- and 90-day mortality rates were 11.0% and 28.5%, respectively. The median length of postoperative hospitalization was 6 days, with 30-day readmission occurring in 7.5% of patients. CONCLUSIONS: The majority of elderly MPM patients in the US are observed, which was associated with poorer OS than chemotherapy and/or surgery. Although highly selected surgery/chemotherapy patients were associated with the longest OS, given the high biases in database studies and high perioperative mortality rates, careful patient selection for combined modality approaches in this population is imperative.

Management of brain metastases from large cell neuroendocrine carcinoma of the lung: improved outcomes with radiosurgery.

OBJECTIVES: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare pulmonary tumor, having similar natural history and management strategy as small cell lung cancer. Therefore, the management of brain metastases in these patients has mirrored that of SCLC through the use of whole brain radiation therapy (WBRT). We used the National Cancer Database (NCDB) to look at predictors of stereotactic radiosurgery (SRS) and any potential differences in outcomes for patients with brain metastases from LCNEC. MATERIAL AND METHODS: We queried the NCDB from 2004 to 2015 for patients with LCNEC of the lung with brain metastases that received brain radiation. Univariable and multivariable analyses were performed to identify factors predictive of SRS use and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Out of 9970 patients with LCNEC of the lung we identified 348 with brain metastases. Sixty-eight patients were treated with upfront SRS and 280 were treated with WBRT. Patients that were treated at an academic facility or received chemotherapy as part of upfront treatment were more likely to receive SRS. Univariable analysis revealed improved outcomes with SRS compared to WBRT, with a median OS of 11 months compared to 6 months, respectively (p = .007). Multivariable Cox regression with propensity score confirmed SRS to have improved survival (HR: 0.68, 95%CI: 0.51-0.91, p = .0093). Multivariable Cox regression with propensity score also identified younger age, receipt of chemotherapy, absence of extracranial disease and non-rural locations as additional predictors of improved OS. CONCLUSIONS: Treatment of brain metastases from LCNEC of the lung with SRS was associated with improved survival. For the appropriate patients, upfront treatment of limited brain metastases with SRS may be appropriate.

Grover's Disease Treated With Total Skin Electron Beam Radiotherapy

Persistent Grover's disease can cause significant symptoms of pruritus thereby decreasing quality of life. Many patients undergo successful conservative management of their disease; however, a subset of patients is recalcitrant despite multiple lines of therapy. Accordingly, we present, to our knowledge, the first reported case of recalcitrant Grover's disease treated successfully with radiotherapy. J Drugs Dermatol. 2019;18(4):392-393.

Online Adaptive MRI-Guided Stereotactic Body Radiotherapy for Pancreatic and Other Intra-Abdominal Cancers.

A 1.5T MRI combined with a linear accelerator (Unity®, Elekta; Stockholm, Sweden) is a device that shows promise in MRI-guided stereotactic body radiation treatment (SBRT). Previous studies utilized the manufacturer's pre-set MRI sequences (i.e., T2 Weighted (T2W)), which limited the visualization of pancreatic and intra-abdominal tumors and organs at risk (OAR). Here, a T1 Weighted (T1W) sequence was utilized to improve the visualization of tumors and OAR for online adapted-to-position (ATP) and adapted-to-shape (ATS) during MRI-guided SBRT. Twenty-six patients, 19 with pancreatic and 7 with intra-abdominal cancers, underwent CT and MRI simulations for SBRT planning before being treated with multi-fractionated MRI-guided SBRT. The boundary of tumors and OAR was more clearly seen on T1W image sets, resulting in fast and accurate contouring during online ATP/ATS planning. Plan quality in 26 patients was dependent on OAR proximity to the target tumor and achieved 96 ± 5% and 92 ± 9% in gross tumor volume D90% and planning target volume D90%. We utilized T1W imaging (about 120 s) to shorten imaging time by 67% compared to T2W imaging (about 360 s) and improve tumor visualization, minimizing target/OAR delineation uncertainty and the treatment margin for sparing OAR. The average time-consumption of MRI-guided SBRT for the first 21 patients was 55 ± 15 min for ATP and 79 ± 20 min for ATS.

A target definition based on electroanatomic maps for stereotactic arrhythmia radioablation.

PURPOSE: Identifying the target region is critical for successfully treating ventricular tachycardia (VT) with single fraction stereotactic arrhythmia radioablation (STAR). We report the feasibility of target definition based on direct co-registration of electroanatomic maps (EAM) and radioablation planning images. MATERIALS AND METHODS: The EAM consists of 3D cardiac anatomy representation with electrical activity at endocardium and is acquired by a cardiac electrophysiologist (CEP) during electrophysiology study. The CEP generates an EAM using a 3D cardiac mapping system anticipating radioablation planning. Our in-house software read these non-DICOM EAMs, registered them to a planning image set, and converted them to DICOM structure files. The EAM based target volume was finalized based on a consensus of CEPs, radiation oncologists and medical physicists, then expanded to ITV and PTV. The simulation, planning, and treatment is performed with a standard STAR technique: a single fraction of 25 Gy using volumetric-modulated arc therapy or dynamic conformal arc therapy depending on the target shape. RESULTS: Seven patients with refractory VT were treated by defining the target based on registering EAMs on the planning images. Dice similarity indices between reference map and reference contours after registration were 0.814 ± 0.053 and 0.575 ± 0.199 for LV and LA/RV, respectively. CONCLUSIONS: The quality of the transferred EAMs on the MR/CT images was sufficient to localize the treatment region. Five of 7 patients demonstrated a dramatic reduction in VT events after 6 weeks. Longer follow-up is required to determine the true safety and efficacy of this therapy using EAM-based direct registration method.

Dosimetric benefits of dynamic conformal arc therapy-combined with active breath-hold in lung stereotactic body radiotherapy.

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t-test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH.

Stereotactic ablative body radiotherapy versus conventionally fractionated radiotherapy for early stage large cell neuroendocrine carcinoma of the lung.

AIM: Some patients with early stage large cell neuroendocrine carcinoma (LCNEC) of the lung are not surgical candidates and will be managed with radiotherapy. We used the national cancer database to identify predictors of stereotactic radiotherapy and compare outcomes. MATERIALS & METHODS: We queried national cancer database for T1-2N0 LCNEC treated with radiation. Logistic regression and Cox regression identified predictors of stereotactic ablative body radiotherapy (SABR) and survival, respectively. RESULTS: We identified 754 patients, with 238 (32%) treated with SABR. Predictors of SABR were distance to facility, no chemotherapy, academic center, T1 and recent year. After propensity matching, median survival was 34.7 months compared with 23.7 months in favor of SABR (p = 0.02). CONCLUSION: SABR for LCNEC has increased over time and was associated with improved survival.

Intensity-modulated radiation therapy in early stage squamous cell carcinoma of the larynx: treatment trends and outcomes.

PURPOSE: Definitive radiotherapy remains a primary treatment option for early stage glottic cancer. Intensity-modulated radiation therapy (IMRT) has emerged as the standard treatment technique for advanced head and neck cancers, whereas three-dimensional conformal radiotherapy (3D-CRT) has remained standard for early glottic cancers. We used the National Cancer Database (NCDB) to identify predictors of IMRT use and effect on outcome in these patients. MATERIALS AND METHODS: We queried the NCDB from 2004-2015 for squamous cell carcinoma of the glottic larynx staged Tis-T2N0 treated with radiation alone. Logistic regression was used to identify predictors of IMRT. Cox regression was used to identify factors predictive of overall survival. Propensity matching was conducted to account for indication bias. RESULTS: We identified 15,627 patients, of which 11% received IMRT. IMRT use rose from 2% in 2004 to 16% in 2015. Predictors of IMRT include: increased comorbidity, T2 stage, urban location, chemotherapy, treatment at an academic center, and later treatment year. Predictors of improved survival were female gender, higher income, lower stage, no chemotherapy, academic facility, and more remote year. There was no difference in survival between 3D-CRT and IMRT across all stages. CONCLUSIONS: The rate of IMRT use for early stage glottic laryngeal cancer has increased over time. There was no difference in outcome in patients receiving IMRT versus 3D-CRT across the cohort.

Trends in Radiation Fractionation for Bone Metastases: A Contemporary Nationwide Analysis.

PURPOSE: Radiation therapy remains an important palliative tool for patients with bone metastases. The guidelines from the American Society for Therapeutic Radiation Oncology recommend the use of fewer fractions based on randomized data. We used the National Cancer Database to examine trends in radiation fractionation for patients with bone metastases. METHODS AND MATERIALS: We queried breast, prostate, and non-small cell lung cancer in the National Cancer Database from 2010 to 2015 for patients with bone metastases at the time of diagnosis who received bone-directed radiation therapy of 8 Gy in 1 fraction, 20 Gy to 24 Gy in 5 to 6 fractions, 30 Gy in 10 fractions, or >30 Gy in 10 fractions. We tabulated the baseline characteristics, and a multivariable logistic regression analysis was used to identify predictors of single-fraction treatment. RESULTS: We identified 17,859 patients who met the study criteria. The median patient age was 67 years, and the majority of patients (67%) had primary prostate cancer. Most patients (62%) received spine treatment. Single-fraction treatment increased over time from 3% in 2010 to 7% by 2015. Use of more protracted courses (>30 Gy in 10 fractions) decreased from 34% to 15% over the same interval. The most commonly used regimen (50%-60% of cases) remained 30 Gy in 10 fractions. Predictors of single-fraction treatment included increased age, no systemic therapy, increasing distance from facility, treatment at an academic center, nonspine/nonskull metastasis, and more recent treatment year. CONCLUSIONS: Use of single-fraction radiation for bone metastases has increased steadily but still accounts for <10% of palliative courses. The use of more protracted regimens has decreased significantly, although 30 Gy in 10 fractions remains the most widely used regiment.

Predictors of chemotherapy and its effects in early stage squamous cell carcinoma of the larynx.

BACKGROUND: Squamous cell carcinoma (SCC) of larynx is a common head and neck cancer. For cases that are node negative, the role of definitive concurrent chemoradiation is unclear and not supported by guidelines but used at provider discretion. To address this knowledge gap, we examined the oncological outcomes with additional chemotherapy and factors correlated with the chemotherapy administration. METHODS: We queried the National Cancer Database for patients with early stage (T2N0M0) laryngeal SCC treated nonsurgically. Multivariable logistic regression identified predictors of chemotherapy. Multivariable Cox regression evaluated predictors of survival. Propensity matching accounted for indication biases. RESULTS: We identified 7181 patients meeting the eligibility criteria, of which 1568 (22%) patients received chemotherapy in addition to radiation. Predictors of chemotherapy use included younger age, Caucasian race, more remote year of treatment, higher grade, sites other than glottis, treatment at a community cancer center, and use of intensity-modulated radiation therapy. Median overall survival was not significantly different in the two arms analyzed-65 months (95% confidence interval [CI] 60, 72months) with chemotherapy compared to 70 months without chemotherapy (95% CI 66, 75 months, P<.37). Predictors for survival on propensity-matched multivariable analysis were increased age, male sex, less education, lower income, higher comorbidity score, receipt of treatment at a community center, and nonglottic sites. CONCLUSIONS: This study shows no clear survival benefit with chemotherapy in early stage disease. Although this implies that chemotherapy should not be routinely delivered, individualized judgment and prospective studies are recommended as the biology behind this interesting finding is undefined. LEVEL OF EVIDENCE: 2C (Outcomes Research).

Patterns of Care and Outcomes in Verrucous Carcinoma of the Larynx Treated in the Modern Era.

Background: Verrucous carcinoma of the larynx (VCL) is a rare form of laryngeal squamous cell carcinoma. We analyzed the National Cancer Database (NCDB) to examine national treatment pattern, identify factors associated with primary radiation therapy (RT), and compare outcomes in patients with Tis-T2 N0 VCL treated primary surgery and primary RT. Methods: We accessed the NCDB from 2004 to 2015 for patients with Tis-T2 N0 VCL and recorded the treatment modality employed. Multivariable logistic regression was used to identify predictors for radiation therapy. Cox regression was used to calculate hazard ratios for survival. A propensity score matched Kaplan-Meier analysis compared primary surgical treatment to definitive radiation. Results: We identified 732 patients with laryngeal verrucous carcinoma from the NCDB. The majority were cTis-T2 (87%) N0 (96%). We identified 286 vs. 110 Tis-T2N0 patients treated primary surgery and with definitive radiation, respectively, for the purpose of this study. Predictors of radiation were treatment at a community center, no insurance, and higher T stage. Cox regression identified increased age, higher comorbidity score, and government insurance as predictive of worse survival. Propensity matching revealed a trend toward worse survival with definitive radiation, with a median survival of 98 months compared to 143 months (p = 0.02). When including only T1-2 lesions, that is, invasive disease, the trend toward increased survival with surgery [98 months vs. 135 months (p = 0.08)] persisted. Conclusion: The results of the present study support the use of surgery in the management of Tis-T2 N0 VCL when organ preservation is possible.

Surgical resection versus stereotactic body radiation therapy in early stage bronchopulmonary large cell neuroendocrine carcinoma.

BACKGROUND: Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is another definitive treatment option for those patients who have not been treated surgically. Comparison of approaches is being explored in NSCLC, but has yet to be compared exclusively in large cell neuroendocrine carcinoma (LCNEC) of the lung. We used the National Cancer Database (NCDB) to conduct such a comparison. METHODS: We accessed the NCDB for patients with LCNEC who were recorded as having lung stage T1-2N0M0 treated with lobectomy/pneumonectomy or SBRT. Multivariable logistic regression identified predictors of SBRT. Multivariable Cox regression was used to identify predictors of survival propensity matching and account for indication bias. RESULTS: A total of 3209 patients met the criteria, of which 238 (7%) received SBRT. The median SBRT dose was 50 Gy (48-60) in four fractions (3-5). Predictors of SBRT were age >68, T1 disease, and most recent year of treatment. Predictors of survival were younger age, surgical treatment, female sex, and T1 disease. After propensity matching, median survival was 57 months versus 35 months in favor of surgical resection, P < 0.0001. CONCLUSION: Surgical resection in comparison to SBRT has improved survival for patients with early stage LCNEC of the lung. SBRT represents a viable treatment alternative for those patients who do not meet the criteria for surgery.

Practice patterns and outcomes following radiation dose de-escalation for oropharyngeal cancer.

OBJECTIVES/HYPOTHESIS: Numerous trials are evaluating radiotherapy (RT) de-escalation for human papillomavirus (HPV)-mediated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Herein, we evaluated the degree to which de-escalated RT is delivered in the United States, as well as comparative outcomes with full-dose RT as stratified for HPV status. STUDY DESIGN: Retrospective database review. METHODS: We identified patients diagnosed with OPSCC in the National Cancer Database, excluding those with stage I/II disease, unknown HPV status, receiving surgery or not receiving external beam radiation therapy to the primary site, receipt of radiation doses >75 or <54 Gy, radiation treatment course duration <25 or >75 days, and unknown or inadequate (<2 months) follow-up. Multivariable logistic regression analysis identified variables associated with delivery of de-escalated RT (<66 Gy). Overall survival of HPV+ and non-HPV-mediated (HPV-) disease was compared between full-dose and de-escalated approaches. RESULTS: Altogether, 617 and 551 patients were HPV+ and HPV-, respectively. De-escalated RT was delivered in 16.9% HPV+ and 15.2% of HPV- disease, respectively. Older patients and omission of systemic therapy were more likely to receive de-escalated RT. In HPV+ patients, 3- and 5-year survival rates were 83% and 80% in the de-escalated cohort versus 83% and 78% in the full-dose group (P = .83). In HPV- patients, corresponding 3- and 5-year survival rates were 29% and 23% versus 61% and 51% (P = .001). CONCLUSIONS: National utilization of de-escalated RT for OPSCC is low (15%-20%), but does not seem to impact overall survival in HPV+ (but not HPV-) patients. The caveats of this heterogeneous, retrospective analysis require corroboration from a number of ongoing randomized trials. LEVEL OF EVIDENCE: 2c Laryngoscope, 130:E171-E176, 2020.

Drivers of 30- and 90-day Postoperative Death After Neoadjuvant Chemoradiation for Esophageal Cancer.

BACKGROUND: Neoadjuvant chemoradiation, followed by esophagectomy, is a standard of care for locally advanced esophageal cancers. The ChemoRadiOtherapy plus Surgery versus Surgery alone (CROSS) trial reported a 30-day mortality rate of 6%. We sought to evaluate 30- and 90-day mortality in similar patients in the United States and identify predictors of higher mortality rates. METHODS: The National Cancer Database was used to identify patients with cT3-4/N+ esophageal cancers treated with neoadjuvant chemoradiation followed by esophagectomy. Bivariate univariable and multivariable regression analysis was used to identify predictors of 30- and 90-day mortality. RESULTS: We identified 7691 patients. Readmission within 30 days of surgery occurred in 6.0% of patients. Mortality was 2.9% at 30 days and 7.2% at 90 days. Positive surgical margins conferred a more than doubled risk of 30- and 90-day mortality, 5.5% vs 2.7% and 14.6% vs 6.8% (both P < .001). Facility surgical volume impacted 30-day mortality, whereas readmission was associated with 90-day mortality, both exceeding 10% (P = .004 and P = .001, respectively). In patients undergoing minimally invasive surgery converted to open, 90-day mortality was 12.1% (P < .01). For patients 69 years and older, 90-day mortality was also 12.1% (P < .001). Patients who underwent esophagectomy more than 45 days from completion of chemoradiation also had higher 90-day mortality at 8.3% vs 6.2% (P < .001). CONCLUSIONS: Postoperative death at 30 and 90 days after neoadjuvant chemoradiation and esophagectomy appears to be on par with randomized data. Positive surgical margins, squamous cell carcinomas, age 69 and older, readmission within 30 days, and conversion from a minimally invasive operation to an open operation all carry a 90-day mortality risk exceeding 10%.

Adaptation of a Gamma Knife Icon stereotactic radiosurgery program in the face of the COVID-19 pandemic.

Objective: The COVID-19 pandemic necessitated drastic and rapid changes throughout the field of radiation oncology, some of which were unique to the discipline of radiosurgery. Guidelines called for reduced frame use and reducing the number of fractions. Our institution implemented these guidelines, and herein we show the resultant effect on patient treatments on our Gamma Knife Icon program. Methods: In early March 2020 we rapidly implemented suggested changes according to ASTRO and other consensus guidelines as they relate to stereotactic radiosurgery in the COVID-19 era. We reviewed the GK Icon schedule at our institution between January 01 and April 30, 2020. We documented age, condition treated, technique (frame vs. mask), and number of fractions. We then tabulated and graphed the number of patients, framed cases, and fractions delivered. Results: Seventy-seven patients were treated on the GK Icon over that period, for a total of 231 fractions. The number of unique patients varied from 18 (April) to 22 (January). Of the 77 patients only 5 were treated using a frame. The number of fractions per month decreased significantly over time, from 70 in January to 36 in April. Likewise, the percentage of single fraction cases increased from 4.5% per month in January to 67% in April. Conclusions: The results presented here show that it is possible to quickly and efficiently change work flows to allow for reduced fractionation and frame use in the time of a global pandemic. Multidisciplinary cooperation and ongoing communication are integral to the success of such programs.

Stereotactic body radiation therapy in early-stage NSCLC: historical review, contemporary evidence and future implications.

Clinical use of stereotactic body radiation therapy (SBRT) has increased dramatically over the last 2 decades and is the current standard-of-care in cases of inoperable early stage non-small-cell lung cancer. While surgical resection remains the standard-of-care for operable patients, several ongoing clinical trials are investigating the role of SBRT in these operative candidates as well. Taking into consideration the expanding role and utility of SBRT, this paper will: review the historical basis of SBRT; examine landmark trials establishing the framework for the current body of evidence; discuss areas of active and future research; and identify epidemiological trends that are likely to further increase the use of SBRT.

Stereotactic body radiation therapy versus fractionated radiation therapy for early-stage bronchopulmonary carcinoid.

AIM: To compare trends and outcomes in early stage bronchopulmonary carcinoid (BPC) tumors treated nonoperatively with conventionally fractionated radiotherapy (CFRT) and stereotactic body radiotherapy (SBRT). METHODS/MATERIALS: We queried the National Cancer Database for primary (typical) BPC staged cT1-2N0M0 and treated nonsurgically with lung-directed radiation and ≥1 month of follow-up. Odds ratios were used to predict likelihood of SBRT treatment and multivariable Cox regression determined predictors of survival. RESULTS: Out of 154 patients, 84 (55%) were treated with SBRT and the remainder were treated with CFRT. Although SBRT use was 0% from 2004 to 2007, it varied from 50 to 70% per year thereafter. Propensity-matched Kaplan-Meier analysis revealed improved survival with lung SBRT (median: 66 vs 58 months; p = 0.034). CONCLUSION: SBRT for early stage, primary BPC has increased over time and was associated with higher survival than CFRT.

Stereotactic ablative radiation therapy versus conventionally fractionated radiation therapy for stage I small cell lung cancer.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) recently revised recommendations for inoperable stage I small cell lung cancer (SCLC), having added stereotactic ablative radiotherapy (SABR)/chemotherapy to the historical paradigm of concurrent conventionally-fractionated radiation therapy (CFRT)/chemotherapy. Despite the conformality, convenience, and cost-effectiveness of SABR, the NCCN continues to recommend both CFRT/chemotherapy and SABR/chemotherapy primarily because these approaches have not been comparatively analyzed to date. METHODS: The National Cancer Database was queried for histologically-confirmed T1-2N0M0 SCLC; all patients received chemotherapy. Multivariable logistic regression ascertained factors associated with SABR/chemotherapy. Kaplan-Meier analysis assessed overall survival (OS); multivariable Cox proportional hazards modeling examined factors associated with OS. Survival was also calculated following propensity matching. RESULTS: Of 2,107 patients, 7.1% underwent SABR/chemotherapy, and 92.9% received CFRT/chemotherapy. The median (interquartile range) dose of SABR was 50 (48-54) Gy in 4 (3-5) fractions, and 55.8 (45-60) Gy in 30 (30-33) fractions for CFRT. Patients receiving SABR/chemotherapy were more often older, had T1 disease, treated at academic/integrated network facilities, and managed in more recent years (p < 0.05 for all). Respective median survival figures were 29.2 versus 31.2 months (p = 0.77), which persisted following propensity matching (25.4 versus 34.3 months, p = 0.85). On multivariable analysis, radiotherapeutic technique was not associated with OS (p = 0.95). CONCLUSIONS: For stage I SCLC, SABR/chemotherapy affords statistically equivalent outcomes to CFRT/chemotherapy. Because randomized studies addressing this uncommon scenario would almost certainly suffer from inadequate accrual, these retrospective data should be strongly considered in efforts to institute SABR/chemotherapy as the preferred option for this population.

Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Lung Nodules: A Single Institution Series.

Aim: Lung metastases from an extra-pulmonary origin occasionally present with a limited metastatic disease burden. In cases where metastatectomy is not feasible, stereotactic body radiation therapy (SBRT) represents a non-invasive, efficacious option. We report the outcomes of patients treated with lung SBRT in cases of limited metastatic disease. Methods: We retrospectively reviewed outcomes in 44 patients with 50 lung nodules from various extra-pulmonary malignancies treated with SBRT. Fifty percent of the patients were male and median age was 64. The median number of nodules was 1 and 90% of patients had oligometastatic disease. Thirty-four percent of patients had extra-thoracic disease. Results: Fifty lung nodules were treated with SBRT in 44 patients. Median dose was 48 Gy in 5 fractions with a median biological effective dose (BED) of 100 Gy10. Follow-up imaging was available for review in 96% of nodules. Median follow-up was 17.5 months. One year local control was 82%. BED >72 Gy10 predicted improved local control (90 vs. 57% at 1 year). One year overall survival following SBRT was 66%. There was no difference in overall survival if patients had extra-thoracic disease. Conclusion: Lung SBRT is a safe, effective tool for treatment of limited lung metastases. Dose selection remains important for local control.

Establishing a histology-specific biologically effective dose threshold for lung stereotactic ablative radiotherapy (SABR): Is ≥100 Gy10 enough?

OBJECTIVES: Squamous cell carcinoma (SCC) is associated with worse local control and overall survival (OS) compared to adenocarcinoma (ADC) in patients with early stage non-small cell lung cancer (ES-NSCLC). Biological effective dose (BED) escalation above 100 Gy10 improves tumor control, yet SCC and ADC may respond differentially to BED beyond 100 Gy10. MATERIALS AND METHODS: We queried the National Cancer Database for ES-NSCLC (T1-2N0, Stage I-IIA) patients with SCC or ADC treated with stereotactic ablative radiotherapy (SABR). Receiver operator characteristic (ROC) curve analysis was used to identify the optimal dose threshold for SCC and ADC. Patients were stratified by histology and BED (≥122 Gy10 vs <122 Gy10). Univariable and multivariable analyses identified characteristics predictive of OS. Cox proportional hazard ratios with inverse probability weighting (IPW) were used to mitigate indication bias between the two dose arms. RESULTS: Ultimately 11,084 ES-NSCLC patients with either ADC (n = 6476) or SCC (n = 4608) were eligible for analysis. Calculated optimal BED threshold for both SCC and ADC was 122 Gy10. Univariable analysis demonstrated a median (36 months vs 32 months), 3-year (51% vs 43%), and 5-year (27% vs 22%) OS advantage in SCC patients receiving BED escalation ≥122 Gy10 (p = 0.002). No survival difference was observed in the ADC dose escalation arm (p = 0.650). BED escalation ≥122 Gy10 remained an independent predictor of improved survival on IPW multivariable comparison (p < 0.0001). CONCLUSION: Escalation of BED ≥ 122 Gy10 was an independent prognosticator of improved survival in patients with SCC of the lung post-SABR. No survival benefit was observed for ADC, suggesting a differential response to BED escalation.