Sonam Sharma

National Cancer Database Report on Pneumonectomy Versus Lung-Sparing Surgery for Malignant Pleural Mesothelioma

Introduction: Controversy exists regarding the optimal surgical technique for malignant pleural mesothelioma (MPM). We evaluated national practice patterns and outcomes of MPM treated with extrapleural pneumonectomy (EPP) versus lung‐sparing extended pleurectomy/decortication (P/D). Methods: The National Cancer Database was queried for patients with newly diagnosed MPM undergoing EPP or P/D. Multivariable logistic regression ascertained clinical factors independently associated with P/D receipt. Kaplan‐Meier analysis was used to evaluate overall survival (OS) between cohorts; multivariable Cox proportional hazards modeling was used to evaluate factors associated with OS. Survival was then evaluated between propensity‐matched populations. Results: Overall, 1307 patients (271 undergoing EPP [21%] and 1036 undergoing P/D [79%]) met the criteria. Patients receiving P/D were older (p = 0.028), whereas those undergoing EPP were more likely to live in a rural area (p = 0.044), live farther from the treating facility (p = 0.039), and receive treatment at an academic center (p = 0.050). There were no differences between cohorts in 30‐day readmission or mortality (all p > 0.05). The median OS times in the EPP and P/D groups were 19 versus 16 months, respectively (p = 0.120); no differences were observed after propensity matching (p = 0.540). Conclusions: In this largest analysis of its kind to date, findings from this contemporary cohort demonstrate that P/D comprised most surgical procedures for MPM. Procedure type was influenced by sociodemographic and geographical factors, without observed differences in survival or postoperative mortality and readmission rates between techniques.

Clinical impact of prolonged diagnosis to treatment interval (DTI) among patients with oropharyngeal squamous cell carcinoma

PURPOSE/OBJECTIVE(S) We examined practice patterns using the National Cancer Data Base (NCDB) to determine risk factors for prolonged diagnosis to treatment interval (DTI) and survival outcomes in patients receiving chemoradiation for oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND MATERIALS We identified 6606 NCDB patients with Stage III-IV OPSCC receiving chemoradiation from 2003 to 2006. We determined risk factors for prolonged DTI (>30days) using univariate and multivariable logistic regression models. We examined overall survival (OS) using Kaplan Meier and multivariable Cox proportional hazards models. RESULTS 3586 (54.3%) patients had prolonged DTI. Race, IMRT, insurance status, and high volume facilities were significant risk factors for prolonged DTI. Patients with prolonged DTI had inferior OS compared to DTI⩽30days (Hazard Ratio (HR)=1.12, 95% CI 1.04-1.20, p=0.005). For every week increase in DTI there was a 2.2% (95% CI 1.1-3.3%, p<0.001) increase in risk of death. Patients receiving IMRT, treatment at academic, or high-volume facilities were more likely to experience prolonged DTI (High vs. Low volume: 61.5% vs. 51.8%, adjusted OR 1.38, 95% CI 1.21-1.58; Academic vs. Community: 59.5% vs. 50.6%, adjusted OR 1.26, 95% CI 1.13-1.42; non-IMRT vs. IMRT: 53.4% vs. 56.5%; adjusted OR 1.17, 95% CI 1.04-1.31). CONCLUSIONS Our results suggest that prolonged DTI has a significant impact on survival outcomes. We observed disparities in DTI by socioeconomic factors. However, facility level factors such as academic affiliation, high volume, and IMRT also increased risk of DTI. These findings should be considered in developing efficient pathways to mitigate adverse effects of prolonged DTI.

Definitive dose thoracic radiation therapy in oligometastatic non-small cell lung cancer: A hypothesis-generating study

PURPOSE A subset of patients with minimal extrathoracic disease may benefit from aggressive primary tumor treatment. We report comparative outcomes in oligometastatic non-small cell lung cancer (NSCLC) treated with and without definitive, conventionally fractionated thoracic radiation therapy. METHODS AND MATERIALS We identified consecutive patients with stage IV NSCLC who had an Eastern Cooperative Oncology Group performance status ≤2 and ≤4 total sites of metastatic disease and who had been prescribed ≥50 Gy of thoracic radiation. RESULTS Twenty-nine patients with oligometastatic NSCLC were identified between January 2004 and August 2010. Median survival was 22 months from diagnosis. Four patients (14%) experienced pneumonitis greater than or equal to grade 3; 6 (21%) had esophagitis greater than or equal to grade 3. Local control was associated with improved survival (P = .02). In matched subset analysis, median survival was 9 months (P < .01) in patients who received chemotherapy alone. Median time to local failure was 18 versus 6 months (P = .01). On multivariable analysis, radiation (P < .01; odds ratio [OR], 0.33), fewer metastases (P < .01; OR, 2.14), and female sex (P < .01; OR, 0.41) were associated with improved survival. CONCLUSIONS Definitive dose radiation therapy may improve survival in a select subset of patients with minimal extrathoracic disease in whom local progression is of primary concern. Prospective trials are needed to further evaluate the role of local control in oligometastatic NSCLC.

Effect of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

Micro‐Abstract The role of prophylactic cranial irradiation (PCI) in metastatic small‐cell lung cancer (SCLC) is controversial. Using the National Cancer Database we show that patients treated with PCI have improved survival outcomes. In light of conflicting randomized trials, this study adds information to help guide physician and patient decision‐making about the utility of PCI in metastatic SCLC. Introduction Patients with small‐cell lung cancer (SCLC) have a high incidence of occult brain metastases and are often treated with prophylactic cranial irradiation (PCI). Despite a small survival advantage in some studies, the role of PCI in extensive stage SCLC remains controversial. We used the National Cancer Database to assess survival of patients with metastatic SCLC treated with PCI. Patients and Methods Metastatic SCLC patients without brain metastases were identified. To minimize treatment selection bias, patients with an overall survival (OS) < 6 months were excluded. Cox regression identified variables associated with OS. Patients were propensity score‐matched on factors associated with receipt of PCI or OS. The effect of PCI on OS was examined using Kaplan–Meier estimates. Results In the overall cohort (n = 4257), treatment with PCI (n = 473) was associated with improved survival (hazard ratio, 0.66; 95% confidence interval, 0.60‐0.74; P < .0001). Comparisons of propensity score‐matched cohorts revealed a significant survival benefit for patients who received PCI in median OS (13.9 vs. 11.1 months; P < .0001), as well as 1‐ and 2‐year OS (61.2% vs. 44.0% and 19.8% vs. 11.5%, respectively; P < .0001). This survival benefit persisted even after excluding patients who survived < 9 months (median: 15.3 vs. 12.9 months; P < .0001). In multivariable analysis, predictors of receipt of PCI were Caucasian race, younger age, and lower Charlson–Deyo score. Conclusion Using a modern population‐based data set, we showed that metastatic SCLC patients treated with PCI have significantly improved OS. This large retrospective study helps address the conflicting prospective data.

Impact of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small Cell Lung Cancer: A Propensity Score Matched Analysis of Patients in the National Cancer Database

to receive surgery and more likely to succumb to their cancer compared to their Caucasian (C) counterparts. Recent advancements in surgery (such as minimally invasive techniques) and radiation therapy (such as stereotactic body therapy) have resulted in improved short and long-term outcomes in early stage NSCLC. Herein, we designed a population-based study that sought to understand how racial disparities in the treatment and outcome of stage I NSCLC have changed in the past decade. Materials/Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to retrieve a case list of biopsy-proven stage I NSCLC patients above the age of 60. Patients who were diagnosed between the years of 2004-2012 were selected, excluding any patients without definitive records for local therapy. Patients were divided into one of four racial cohorts: C, AA, American Indian (AI), Asian/Pacific Islander (API), or Unknown (U). Demographics, local therapy, and survival metrics were compared using the following statistical analyses: chi-squared test, Kaplan-Meier method, and Cox multivariate analysis. Survival at 23 months was used as a proxy for 2-year survival to include the 2011 data in the final analysis. Results: There were 62,312 patients who met criteria for analysis. AA and AI were less likely to receive surgery than the typical stage I NSCLC patient (55.9% and 57.6% compared to 66.7% overall, P<.05). Two-year OS for C was 70%, AAwas 65%, AI was 60%, API was 76%, and U was 89% (P<.05). Two-year CSS for C was 79%, AA was 76%, AI was 73%, API was 84%, and U was 91% (P<.05). The median CSS for AI and AA was less than that of the typical stage I NSCLC patient (49 months and 80 months, respectively, compared to 107 months, P<.05). This difference in CSS disappeared on multivariate analysis, largely accounted for by sex (using female as reference, male HR Z 1.17), age (unit RR Z 1.01), treatment (using observation as reference, surgery HR Z 0.44, radiation HR Z 0.70, both surgery and radiation HR Z 0.48), and T stage (using T1 as reference, T2 HR Z 1.25) (all P<.05). Conclusion: Despite advancements in surgery and radiation in the last decade, both AA and AI continue to have higher rates of overall and cancer-specific mortality from early stage NSCLC compared to Caucasians. The poor outcomes in stage I NSCLC in AAs and AIs may be due to the association of these populations with more adverse risk factors, such as older age of diagnosis, male sex, T2 stage, and tendency to forgo surgery and receive no treatment. Author Disclosure: S.M. Dalwadi: None. G. Lewis: None. E. Butler: None. B.S. Teh: None. A. Farach: None.

Trends and Patterns of Utilization of Hypofractionated Postmastectomy Radiotherapy: A National Cancer Database Analysis

Background The acceptance of hypofractionated radiotherapy in treating breast cancer in the breast conservation therapy setting has stimulated interest in hypofractionated postmastectomy radiotherapy (PMRT). We assessed national trends and patterns of utilization of hypofractionated PMRT. Patients and Methods Women 18 years of age or older with breast cancer treated with mastectomy and PMRT to the chest wall with or without regional lymph nodes from 2004 to 2014 were identified from the National Cancer Database. A standard fractionation cohort was defined as patients receiving 180 to 200 cGy per fraction to a total dose of 4500 to 7000 cGy over 5 to 7 weeks, and a hypofractionation cohort was defined as those receiving 250 to 400 cGy per fraction to a total dose of 3000 to 6000 cGy over 2 to 5 weeks. Multivariable logistic regression was used to determine factors associated with hypofractionated PMRT use. Results We identified 113,981 patients who met study criteria. Overall, hypofractionated PMRT use was low (1.1%) although utilization increased over time (P ≤ .001). Older age, greater comorbidity, further distance from treatment facility, treatment at academic facilities, less extensive disease, and recent treatment year were statistically significant predictors of hypofractionation use compared with standard fractionation. Conversely, breast reconstruction and receipt of chemotherapy were negative predictors. Conclusion Because of the absence of high‐level evidence to support its use, hypofractionated PMRT was uncommonly utilized in the United States from 2004 to 2014, although a small increase in use was noted over time. Findings from this study might be useful in designing future studies, and might serve as a baseline for evaluation of future changes in practice patterns. Micro‐Abstract There is growing interest in treating breast cancer with hypofractionated postmastectomy radiotherapy (PMRT). National patterns of hypofractionated PMRT utilization were assessed using the National Cancer Database. Overall, hypofractionated PMRT use was uncommon although it increased over time. Hypofractionated PMRT was used in patients more likely to gain convenience from shorter treatment schedules.

Disparities in Perioperative Radiation Therapy Use in Elderly Patients With Soft-Tissue Sarcoma

PURPOSE The benefit of perioperative radiation therapy in elderly patients with soft-tissue sarcoma (STS) is unclear due to the underrepresentation of elderly patients in clinical trials. We assessed patterns of care and overall survival (OS) associated with perioperative radiation therapy use in this population. METHODS AND MATERIALS Elderly patients (≥70 years) with high-grade STS who underwent surgery with or without perioperative radiation therapy from 2004 to 2013 were identified from the National Cancer Database. A nonelderly cohort (<70 years) was also identified for secondary comparative analyses. The association between perioperative radiation therapy use and OS was assessed using propensity score-weighted Cox proportional hazards analyses. Relative survival was calculated using national life tables to assess the impact of radiation therapy on estimated sarcoma-specific survival in elderly and nonelderly patients. Patterns of care were assessed using multivariable logistic regression analyses. RESULTS Of 6978 elderly patients, 3549 (51%) underwent surgery alone, and 740 (11%) and 2,679 (38%) received pre- and postoperative radiation therapy, respectively. Elderly patients received radiation therapy less commonly than did nonelderly patients (49% vs 52%, P < .001) despite presenting with higher grade tumors (grade 3, 86% vs 80%, P < .001) and experiencing more frequent positive surgical margins (23% vs 16%, P < .001). On propensity score-weighted analyses, preoperative (hazard ratio = 0.64, 95% confidence interval: 0.54-0.77, P < .001) and postoperative (hazard ratio = 0.72, 95% confidence interval: 0.67-0.77, P < .001) radiation therapy use was associated with improved OS compared with surgery alone. These associations were robust to landmark analyses of patients surviving at least 12 months. Radiation therapy use resulted in a greater magnitude of 5-year relative survival improvement in elderly than nonelderly patients. CONCLUSIONS There is an overall and an age-disparate underuse of perioperative radiation therapy in elderly patients with high-grade STS despite radiation therapy being associated with improved OS. Further research is warranted to minimize gaps in care for elderly patients.

Quality of Life of Postoperative Photon versus Proton Radiation Therapy for Oropharynx Cancer

Purpose: Quality of life (QOL) for patients with oropharyngeal squamous cell cancer is negatively affected by conventional radiation (RT) owing to radiation exposure to normal tissues. Proton therapy, via pencil beam scanning (PBS), can better spare many of these tissues, and may thereby improve QOL. Patients and Methods: Patient-reported outcomes were prospectively collected from patients treated from April 2013 to April 2015. Patients were treated with PBS or intensity-modulated radiation therapy (IMRT) via volumetric arc therapy after transoral robotic surgery. Validated QOL questionnaires were collected before RT, and 3, 6, and 12 months post RT. Results: Sixty-four patients were treated with adjuvant RT after transoral robotic surgery, 33 (52%) with volumetric arc therapy, and 31 (48%) with PBS. Both groups were similar in terms of age, site, stage, and dose delivered. Patients receiving PBS had significantly less dose to many normal structures than those receiving IMRT. These dosimetric advantages with PBS were reflected in higher scores in head and neck specific, as well as general, QOL measures. Most notable was significantly less xerostomia with PBS, on multiple patient-reported outcomes at multiple timepoints (6 and 12 months). Conclusion: Pencil beam scanning, when compared to IMRT, confers a significant dosimetric advantage to many normal organs at risk, with a corresponding benefit in multiple patient-reported QOL parameters in patients receiving adjuvant RT for oropharyngeal squamous cell cancer.

Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of Brain Metastases

Brain metastases traditionally carried a poor prognosis with an overall survival of weeks to months in the absence of treatment. Radiation therapy modalities include whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). WBRT delivers a relatively low dose of radiation, has neurocognitive sequelae, and has not been investigated for its immunostimulatory effects. Furthermore, WBRT exposes the entire intracranial tumor immune microenvironment to radiation. SRS delivers a high dose of conformal radiation with image guidance to minimize dose to surrounding normal brain tissue, and appears to promote anti-tumor immunity. In parallel with many of these discoveries, immune checkpoint inhibitors (ICIs) have demonstrated a survival advantage in multiple malignancies commonly associated with brain metastases (e.g., melanoma). Combination SRS and ICI are theorized to be synergistic in anti-tumor immunity directed to brain metastases. The purpose of this review is to explore the synergy of SRS and ICIs, including pre-clinical data, existing clinical data, and ongoing prospective trials.

A Single-institution Comparison of Cetuximab, Carboplatin, and Paclitaxel Induction Chemotherapy Followed by Chemoradiation (CRT) Versus CRT for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-SCCHN).

Objectives:Comparisons of induction chemotherapy (IC) against upfront chemoradiation (CRT) for locally advanced head and neck cancer (LA-HNSCC) have demonstrated no differences except greater toxicity with IC. Effective induction regimens that are less toxic are therefore warranted. To inform future efforts with IC, we present our institutional experience comparing a less toxic IC regimen to CRT. Methods:We included patients with LA-HNSCC treated with organ-preservation CRT (+/−induction) between 2008 and 2011. Patients were of age above 18 years, ECOG performance status 0-1, and had minimum 6 months follow-up. IC consisted of 8 weekly cycles of cetuximab, carboplatin, and paclitaxel followed by CRT. The CRT regimen was platinum based, with cetuximab reserved for patients contraindicated to receive platinum. Results:Of 118 patients, 24 (20%) received IC and 94 (80%) received CRT. Median follow-up was 17 (IC) and 19 (CRT) months (P=0.05). There were no differences in toxicity between the groups. IC patients were more likely male, with more advanced tumor and nodal stage. Even when controlling for these factors, IC was still associated with worse locoregional control (HR=3.6, P=0.02), distant metastasis–free survival (HR=5.3, P=0.02), and overall survival (HR=5.1, P<0.01). Conclusions:IC patients had greater disease burden than those receiving CRT. IC was well tolerated, but with significant rates of locoregional and systemic failures. Given the retrospective nature of the study, our findings are not meant to be definitive or conclusive, but rather suggestive in directing future efforts with IC. For now, we favor CRT as the standard option for treatment of inoperable LA-HNSCC.