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A randomized trial of lobectomy versus segmentectomy for small-sized (≤ 20 mm) non-small cell lung cancer (NSCLC) showed that patients who had undergone segmentectomy had a significantly longer overall survival (OS) than those who had lobectomy. More attention is needed regarding the required extent of thoracic lymphadenectomy in patients with small-sized NSCLC who undergo sublobar resection.The National Cancer Database was queried for patients with clinically node-negative NSCLC ≤ 20 mm who had undergone sublobar resection between 2004 and 2017. OS of NSCLC patients by the number of lymph node dissections (LNDs) was analyzed using log-rank tests and Cox proportional hazards model. The cutoff value of the LNDs was set to 10 according to the Commission on Cancer's recommendation.This study included 4379 segmentectomy and 23,138 wedge resection cases. The sequential improvement in the HRs by the number of LNDs was evident, and the HR was the lowest if the number of LNDs exceeded 10. Patients with ≤ 9 LNDs had a significantly shorter OS than those with ≥ 10 LNDs (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.40-1.61, P 0.0001). Multivariable analysis revealed that performing ≤ 9 LNDs was an independent factor for predicting OS (HR for death: 1.34, 95% CI 1.24-1.44, P 0.0001). These results remained significant in subgroup analyses by the type of sublobar resection (segmentectomy, wedge resection).Performing ≥ 10 LNDs has a prognostic role in patients with small-sized NSCLC even if the resection is sublobar.

Mucoepidermoid carcinoma (MEC) represents 10-15% of salivary neoplasms. Due to their low incidence, it is challenging to conduct clinical trials and develop treatment guidelines. Although surgery is the most common approach for a resectable tumor, various treatment options such as chemotherapy, radiotherapy, and immunotherapy have been investigated. There is a need to implement a standardized treatment protocol to effectively manage MEC as it is a common histological subtype. Furthermore, it has become essential to assess chromosomal and genetic abnormalities recently identified with MEC, including alterations of

Although concurrent chemoradiation has been the standard of care for unresectable stage III non-small cell lung cancer (NSCLC) due to increased survival and decreased disease progression, patients with poor performance status cannot tolerate chemotherapy toxicity well. Durvalumab, an immune checkpoint inhibitor targeting the programmed death receptor-1 (PD-1) / programmed death-ligand 1 (PD-L1) axis, demonstrated efficacy as maintenance therapy after definitive chemoradiation. However, the role of immunotherapy in those who cannot tolerate chemoradiation is unclear.This retrospective case series reports adult patients with PD-L1-expressing stage III NSCLC diagnosed at Parkview Cancer Institute from 2019-2021 and treated initially with pembrolizumab followed by sequential consolidation chest radiation (CXRT) without cytotoxic chemotherapy.Four cases of stage IIIA squamous cell carcinoma were disease-controlled by this approach, with two partial and one complete response. One case of stage IIIC adenocarcinoma had progressive disease with brain metastasis prior to CXRT.This case series suggests that pembrolizumab with sequential CXRT may be beneficial for stage III NSCLC patients with high PD-L1 expression, but additional studies are needed to confirm this hypothesis.

Background: Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, the role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined. Methods: Using the National Cancer Database (NCDB), Stage IV lung LCNEC cases diagnosed from 2014 to 2016 were analyzed. Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion, radiation, chemotherapy, and immunotherapy. Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analysis. Results: Among 661 eligible cases, 37 patients were treated with immunotherapy. No significant association between use of immunotherapy and clinical demographics was observed except for use of chemotherapy (p=0.0008). Chemotherapy was administered in 34 (92%) and 406 (65%) in immunotherapy and non-immunotherapy groups, respectively. Use of immunotherapy was associated with improved overall survival (Log-rank p=0.0018). Landmark analysis in the immunotherapy group showed 12 and 18-month survivals of 34.0% and 29.1%, respectively, whereas those in the non-immunotherapy group were 24.1% and 15.0%, respectively. Multivariate analysis demonstrated that female sex (HR=0.79, p=0.0063), liver metastases (HR=0.75, p=.0392), surgery (HR= 0.50, p

Immunocheckpoint inhibitors (ICIs) have become a standard pharmacological therapy in non‐small cell lung cancer (NSCLC). Because brain metastases (BMs) have historically been listed as exclusion criteria in previous clinical trials involving ICIs in advanced NSCLC, the survival benefit from ICI in NSCLC patients with BMs remains unclear. The National Cancer Database was queried for stage IV NSCLC patients with or without BMs between 2014 and 2015. Overall survival (OS) of stage IV NSCLC patients who received immunotherapy and that of stage IV NSCLC patients who did not receive immunotherapy were compared according to the presence or absence of BMs. Multivariable logistic analyses identified the clinical characteristics predictive of overall survival. A propensity score analysis was conducted with the aim of adjusting the potential biases arising from the clinical characteristics. This study included 42,512 patients with stage IV NSCLC; 11,810 patients with BMs and 30,702 patients without BMs. In univariate analysis, stage IV NSCLC patients with BMs treated with immunotherapy had a significantly longer OS than those without immunotherapy after propensity score matching (median OS: 12.8 vs 10.1 months, hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.72–0.89, p, In previous clinical trials investigating efficacy of immune checkpoint inhibitors (ICIs) on advanced non‐small cell lung cancer (NSCLC), brain metastases (BMs) have been listed as exclusion criteria. Thus, the survival benefit from ICIs in NSCLC patients with BMs had been unclear. This retrospective study shows that overall survival in NSCLC patients with BMs was significantly improved by ICIs at levels comparable to those without BMs. ICIs may be promising treatment options for NSCLC patients with BMs.

Role of adjuvant radiation therapy in stage III (N2) non-small cell lung cancer has been controversial over the decades. Recent large, randomized trials have demonstrated that adjuvant radiation did not improve overall survival or disease-free survival; however, the trials either excluded or enrolled very few cases that have undergone neoadjuvant chemotherapy. Role of adjuvant radiation after neoadjuvant chemotherapy remains unclear. Whether the use of adjuvant radiation is associated with improved overall survival in those who have received neoadjuvant chemotherapy, especially in a subgroup of patients with persistent N2, is unknown.Patients with clinical stage III (N2) non-small cell lung cancer diagnosed from 2004 through 2017 were queried to National Cancer Database. Eligibility criteria included completely resected (R0), pathological diagnosis, neoadjuvant multi-agent chemotherapy, information regarding post-surgical N2 status (persistent versus downstaged to pN0-1), adjuvant radiation (45 Gy+ versus none), and American Joint Commission on Cancer staging version (6th versus 7th). Those who have received neoadjuvant radiation with any dose or adjuvant radiation with less than 45 Gy total dose were excluded. Kaplan-Meier and log-rank tests were used for survival analyses. Propensity-score matching analysis was used for validation. All statistical analyses were two-sided, and p 0.05 was required for statistical significance.A total of 1,855 patients met the eligibility criteria for analysis. In the overall cohort, there was a significant difference in overall survival between persistent N2 (Cohort P: N = 854, median survival 50.7 months) and downstaged N (Cohort D: N = 1,001, median survival 82.7 months). The use of adjuvant radiation showed a non-significant detrimental effect in overall survival in the overall and Cohort D (univariate p-values 0.27 and 0.077, respectively); however, both univariate and multivariate analyses demonstrated a significant improvement in overall survival in Cohort P (p = 0.004 and 0.028, respectively). These findings are also verified by propensity-score matching analysis (p = 0.0347).This large-scale retrospective analysis suggests that adjuvant radiation may still have a role in persistent N2 disease after neoadjuvant chemotherapy. Further investigations are warranted.

Occult primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Very limited retrospective data are available in the literature. Its prognosis and response to systemic chemotherapy have not been investigated with large scale data.Using National Cancer Database (NCDB), cases that had undergone radiation therapy without surgery for N2-3M0 NSCLC were selected. Demographics and survival data were compared between T0 and T1-4 groups. Survival analyses were conducted with Kaplan-Meier and log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses.Between 2004 and 2016, 84,263 and 458 cases met criteria for unresectable stage III NSCLC with T1-4 and T0 stage, respectively. T0 status was associated with younger age, recent diagnosis (year 2010-2016), adenocarcinoma histology, N3 stage, and use of chemotherapy. Survival analysis demonstrated that those with T0 status had prolonged overall survival as compared to T1-4 counterparts in both overall and chemotherapy groups (p 0.0001 for each). Five-year overall survival rates for T0 and T1-4 groups were 30.5% and 12.7% in all groups, and 33.6% and 14.6% in chemotherapy groups, respectively. Propensity score matching also demonstrated a statistically significant difference in overall survival (p 0.0001). These findings are confirmed by independent analysis using Surveillance, Epidemiology, and End Results Program (SEER).This large hospital-based study demonstrates the favorable prognosis for T0 status in the setting of unresectable stage III NSCLC. Researchers may consider it as distinct stage (e.g., stage IIC) for future studies.

Introduction The National Cancer Database (NCDB) is a clinical oncology database utilized by many researchers and clinicians internationally. We sought to investigate the various trends in data of two of the most common cancers, breast and lung, published using the NCDB. Materials and methods We selected a multitude of pre-determined variables for analysis. We then performed two separate literature searches using an advanced PubMed search builder, and the data was combined to determine each variables' association with journal impact factor (IF) using both univariate and multivariate analyses. Results A total of 191 published studies were identified. We found that a journal IF > 5 was associated with a publication year prior to 2017 (univariate analysis OR 2.68, 95% CI 1.38-5.21, p-value 0.004 and multivariate analysis OR 3.47, 95% CI 1.62-7.42, p-value 0.001) and a sample size > 10,000 (univariate analysis OR 3.27, 95% CI 1.43-7.50, p-value 0.005 and multivariate analysis OR 4.68, 95% CI 1.89-11.6, p-value 0.0008). Variables such as number of authors, region, cancer type, stage, treatment outcome and treatment incidence were not significant for an association with an IF >5. Conclusion Based on our data, studies published after 2017 using the NCDB were associated with a lower IF. This could suggest that the quality of the NCDB data may be declining over time, or NCDB is becoming more widely used. .

Immune checkpoint inhibitors (ICIs) have become standard pharmacological therapies in patients with non‐small‐cell lung cancer (NSCLC). Because elderly patients with NSCLC are often excluded from clinical trials as a result of lower functional capacity or comorbidities, the prognostic impact of chronological age on the efficacy of ICIs is unclear. The National Cancer Database was queried for stage IV NSCLC patients between 2014 and 2015. Associations between ICI therapy and clinical characteristics were assessed using chi‐squared tests. Kaplan–Meier curves were compared using the log‐rank test. A Cox proportional hazards model was used to identify clinical characteristics predictive of overall survival (OS). This study included 24 136 patients with stage IV NSCLC aged ≥75 years and 62 037 patients with stage IV NSCLC aged, In stage IV non‐small‐cell lung cancer patients aged

The American Society of Clinical Oncology and Friends of Cancer Research submitted recommendations to the FDA to reduce barriers in clinical trial participation. They proposed the removal of several specific exclusion criteria, including brain metastasis. Clinical trials involving small cell lung cancer (SCLC) have varying exclusion criteria regarding brain metastasis. We completed an online search of clinicaltrials.gov for the query “SCLC, extensive stage.” The trials were classified into a group of strict exclusion, allowed only if treated, allowed without treatment, or undefined. Relationships between status of brain metastasis in exclusion criteria and study characteristics (trial status, trial design, sponsor, location, and treatment groups) were investigated by Chi-squared test. The trends of exclusion status were investigated by a comparison against the variable time. Of the 204 eligible trials, 32 strictly excluded any form or history of CNS metastases, 129 allowed patients that are undergoing or have undergone CNS-specific therapy, 9 allowed patients without any CNS-specific therapy, and 34 did not mention any criteria involving CNS metastases. Studies conducted outside the United States and with single systemic therapy were associated with strict exclusion of brain metastasis (p = 0.026 and 0.039, respectively). The proportion of clinical trials with strict exclusion has remained around 15% for the past few decades. Non-US and single systemic therapy studies are more commonly associated with strict exclusion of brain metastasis in ES-SCLC trials. The strict exclusion of brain metastases in clinical trials has remained relatively constant for the past few decades.

IMPORTANCE: Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non–small cell lung cancer (NSCLC). OBJECTIVE: To evaluate treatment outcomes and safety of pembrolizumab plus cCRT in stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The phase 2, nonrandomized, 2-cohort, open-label KEYNOTE-799 study enrolled patients between November 5, 2018, and July 31, 2020, from 52 academic facilities and community-based institutions across 10 countries. As of October 28, 2020, median (range) follow-up was 18.5 (13.6-23.8) months in cohort A and 13.7 (2.9-23.5) months in cohort B. Of 301 patients screened, 216 eligible patients with previously untreated, unresectable, and pathologically/radiologically confirmed stage IIIA/IIIB/IIIC NSCLC with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) were enrolled. INTERVENTIONS: Patients in cohort A (squamous/nonsquamous) received 1 cycle (3 weeks) of carboplatin (area under the curve [AUC] 6 mg/mL/min), paclitaxel (200 mg/m(2)), and pembrolizumab (200 mg), followed by carboplatin (AUC 2 mg/mL/min) and paclitaxel (45 mg/m(2)) once weekly for 6 weeks and 2 cycles of pembrolizumab plus standard thoracic radiotherapy. Patients in cohort B (nonsquamous) received 3 cycles of cisplatin (75 mg/m(2)), pemetrexed (500 mg/m(2)), and pembrolizumab (200 mg) every 3 weeks and thoracic radiotherapy in cycles 2 and 3. Patients received 14 additional cycles of pembrolizumab. MAIN OUTCOMES AND MEASURES: Coprimary end points were objective response rate per RECIST v1.1 by blinded independent central review and incidence of grade 3 to 5 pneumonitis. RESULTS: A total of 112 patients received treatment in cohort A (76 men [67.9%]; median [range] age, 66.0 [46-90] years; 66 patients [58.9%] with programmed cell death ligand 1 [PD-L1] tumor proportion score ≥1%) and 102 patients received treatment in cohort B (62 men [60.8%]; median [range] age, 64.0 [35-81] years; 40 patients [39.2%] with PD-L1 tumor proportion score ≥1%). Objective response rate was 70.5% (79 of 112; 95% CI, 61.2%-78.8%) in cohort A and 70.6% (72 of 102; 95% CI, 60.7%-79.2%) in cohort B. Median duration of response was not reached, but 79.7% and 75.6%, respectively, had response duration of 12 months or longer. Grade 3 or higher pneumonitis occurred in 9 of 112 patients (8.0%) in cohort A and 7 of 102 (6.9%) in cohort B. Grade 3 to 5 treatment-related adverse events occurred in 72 of 112 (64.3%) and 51 of 102 (50.0%) patients, respectively. CONCLUSIONS AND RELEVANCE: The findings of this phase 2, nonrandomized, 2-cohort study suggest promising antitumor activity of pembrolizumab plus cCRT and manageable safety in patients with previously untreated, locally advanced, stage III NSCLC.

Prognosis of extensive stage small cell lung cancer (ES-SCLC) remains poor. Previous randomized trials suggested consolidation chest radiation (CXRT) has a modest survival benefit; however, its role in subgroups of ES-SCLC, especially ipsilateral pleural effusion (IPE), is unknown. Using National Cancer Database (NCDB), 283,347 ES-SCLC cases diagnosed between 2004 and 2017 were screened. Eligible cases must have been staged with 7th edition of staging system and have information about clinical T and N stage, and minimum follow-up of one month. Role of CXRT was examined in M1a, M1b, and IPE subgroups. Surveillance, Epidemiology, and End Results Program (SEER) was analyzed as independent validation. Univariate, multivariate analyses were conducted with cox proportional hazard model. A P value

8508 Background: Primary analysis (database cutoff, Oct 28, 2020) of the global KEYNOTE-799 study (NCT03631784) in patients (pts) with unresectable, locally advanced stage III NSCLC, showed that pembrolizumab (pembro; anti–PD-1) plus cCRT resulted in an ORR of 70.5% in cohort A (n = 112; squamous and nonsquamous) and 70.6% in cohort B (n = 102; nonsquamous only) and grade ≥3 pneumonitis in 9 (8.0%) and 7 (6.9%) pts, respectively. We present updated outcomes with 1 y of additional follow-up. Methods: In this nonrandomized, phase 2 study, eligible pts were aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA-C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received carboplatin AUC 6 plus paclitaxel 200 mg/m2 and pembro 200 mg for one 3-wk cycle, followed by carboplatin AUC 2 plus paclitaxel 45 mg/m2 QW for 6 wks plus 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous) received 3 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and pembro 200 mg Q3W plus standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Results: Of 216 pts enrolled in this study, 112 in cohort A and 102 in cohort B received treatment. Median (range) time from first dose to database cutoff (Oct 18, 2021) was 30.2 (25.3–35.5) mo in cohort A and 25.4 (14.5–35.2) mo in cohort B. ORR (95% CI) was 71.4% (62.1%–79.6%) in cohort A and 75.5% (66.0%–83.5%) in cohort B. Median duration of response (DOR) and OS were not reached (NR) in both cohorts; median PFS was 30.6 mo in cohort A, and NR in cohort B (Table). ORR was 66.7% in pts with PD-L1 TPS 2 y of follow-up, pembro plus cCRT continues to demonstrate robust and durable responses, regardless of PD-L1 TPS and tumor histology, promising survival outcome and manageable safety in pts with previously untreated, locally advanced stage III NSCLC. Clinical trial information: NCT03631784. [Table: see text]

Background Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. Patients and methods Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. Results In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). Conclusions SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.

Background and Hypothesis: Non-Small Cell Lung Cancer (NSCLC) constitutes the largest proportion of lung cancers and is the foremost cause of mortality associated with cancer around the world. Of patients with non-small cell lung cancer, approximately 15% of Caucasians and 30% of Asians have activating mutations in the epidermal growth factor receptor (EGFR) gene. Numerous studies have indicated increased progression free survival after treatment with tyrosine kinase inhibitors (TKI). However, the most efficacious combination of drugs, whether TKIs, chemotherapy, or anti-angiogenesis, is still unknown. This literature review will be constructed to determine whether tyrosine kinase inhibitor targeted therapy in combination with chemotherapy or anti-angiogenesis drugs is more effective in prolonging progression free survival in EGFR-mutated NSCLC as opposed to tyrosine kinase inhibitor targeted therapy alone. Project Methods: The methodology of this proposed literature review is an online search of PubMed, Journal of Clinical Oncology, and important scientific conferences. The treatment interventions consist of tyrosine kinase inhibitor targeted therapy in combination with chemotherapy and tyrosine kinase inhibitor targeted therapy alone. The projected outcome is an increase in progression free survival and overall survival. The proposed data analysis consists of constructing a forest plot in order to display the results. Results: The results are expected to support the hypothesis, that combination treatment with TKI and chemotherapy will allow patients with an opportunity to prolong their progression-free survival. The forest plot is expected to indicate a progression-free survival hazard ratio that favors combination therapy. P-values will be included to indicate statistically significant results. Conclusion and Potential Impact: The importance of finding the answer to this hypothesis is that it will improve treatment outcomes for patients with NSCLC. It will provide patients with a strong alternative to chemotherapy or tyrosine kinase inhibitor therapy alone. Most importantly, it will provide patients with an avenue to increase their progression-free survival.

Introduction T components of the current eighth edition of lung cancer American Joint Commission on Cancer (AJCC) staging assignment include size of primary tumor and others such as chest wall invasion. The role of the presence of multiple T3 descriptors in prognosis remains unknown. Methods Using the National Cancer Database and the AJCC seventh edition, pathologically staged (R0) N0M0 NSCLC cases diagnosed in 2010 to 2016 were analyzed. The selected cases had primary size larger than 5 cm or staged as T3 by the AJCC seventh edition despite the size of less than 5 cm. T3 descriptor status according to the eighth edition was defined as single descriptor ("T3-single") with primary size of 5 to 7 cm or size less than 5 cm and T3 based on the seventh edition ("T3-other") or multiple descriptor ("T3-multi") with presence of both descriptors. Survival analysis was performed with validation of multivariate analyses. Results Of the 108,632 surgically resected pathologically staged N0M0R0 NSCLC cases, 9931 met the following criteria: 8955 as T3-single (4381 as T3-size, 4574 as T3-other) and 884 as T3-multi. Univariate and multivariate analyses revealed that T3-multi had significantly worse overall survival than T3-single with a median survival of 37.3 versus 69.3 months, respectively. Propensity score matching analysis validated the statistical significance. Exploratory analysis also revealed that the survival of the T3-multi group is similar to that of the T4 groups. Conclusions Our retrospective analysis using the National Cancer Database suggests that prognosis of patients with multiple T3 descriptors is substantially worse than those with single descriptors. Further research may be required to accurately define the prognosis of NSCLC for future staging update.

BACKGROUND: Most patients with pancreatic cancer have non-resectable disease at the time of diagnosis and usually die within 6–12 months. Despite indications in other solid tumors, the role of immunotherapy (IO) is unknown for late stage, advanced pancreatic cancer. METHODS: Using the National Cancer Database (NCDB), cases of Stage IV pancreatic cancers diagnosed in the period of 2014–2016 with at least 30-day follow up were retrospectively analyzed. The following clinical demographics were included: age (younger than 70 vs. older than 70), sex (male vs. female), race (whites vs. others), insurance (uninsured vs. insured), type of institution (academic vs. nonacademic), liver metastasis (yes vs. no), lung metastasis (yes vs. no), external beam radiation (yes vs. no), systemic chemotherapy (yes vs. no) and IO (yes vs. no). survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Multivariable Cox proportional hazard models and propensity score matching analysis were also utilized. A P value

Background Although randomized trials demonstrated survival benefit of adjuvant chemotherapy, previous reports have suggested that its use in elderly populations for early stage non-small cell lung cancer (NSCLC) was infrequent. The current status of adjuvant chemotherapy in this population is unknown. Methods Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined the incidence of chemotherapy in resected stage II-III NSCLC between 2004 and 2015. Staging was determined according to the American Joint Committee on Cancer (AJCC) 6th version. Cases were grouped by age (20-69, 70-79, and 80+). Trends in use of chemotherapy by age group were assessed by univariate and multivariate analyses. Results A total of 35,009 cases were selected as surgically resected stage II-III NSCLC. Use of chemotherapy was 66.9%, 48.2%, 25.0% in age 20-69, 70-79, 80+, respectively. Multivariate analysis demonstrated that younger age [20-69] and recent year [2010-2015] of diagnosis were associated with increased use of chemotherapy. Chemotherapy use increased from 2004 to 2015 by 11.0%, 18.3%, and 11.3% in age 20-69, 70-79, 80+, respectively. In the age 70-79 group, increased use of chemotherapy was greater in stage II (24.3%) than stage III (14.1%). Five-year overall survival in age 70-79 group mildly increased by 7.6% from 2004 to 2011. Conclusions This study suggests that use of adjuvant chemotherapy in the elderly population increased primarily in age 70-79. Few patients in the 80+ age group received adjuvant chemotherapy even in recent years.

Recent studies have demonstrated that there are differences among races in efficacy, tolerance and other outcomes in oncologic care. Some of these differences may be explained by different pharmacogenetics; however, social and environmental factors that can affect oncology practice are relatively underestimated. In this review we will focus on differences in environment, education and research between Japan and the US when it comes to lung cancer clinical practice. Such social differences seem to derive from historical reasons and continue to influence clinicians and researchers who manage lung cancer. Understanding the differences might help us conduct collaborative research in the future.

Lung cancer is the major cause of cancer mortality in the USA. In this review, we aim to provide a general update on the current status of non-small cell lung cancer (NSCLC) management. Novel approaches in the diagnosis and treatment of non-small cell lung cancer have been made recently and this was revolutionary in the way lung cancer management has changed even-though the improvement in overall survival remains modest. Furthermore, lung cancer screening using low-dose computed tomography scan has shown benefit in high-risk populations. The diagnosis of lung cancer has evolved over the last couple of years with the new endoscopic modalities. Targeted therapies and immunotherapies, including tyrosine kinase inhibitors and checkpoint inhibitors, constitutes the current progress made in the treatment of lung cancer, and have helped improve survival in the metastatic setting. Many trials are ongoing in investigating other biomarkers.

Background: Our previous study suggested NR4A2, a subfamily member of orphan nuclear receptors, is essential for survival of human cancer cells such as mucoepidermoid carcinoma (MEC). Methods: We conducted high throughput drug screening for NR4A2 inhibitors as a novel therapeutic modality. Positive screening was performed using a luciferase reporter vector containing NR4A2 binding sequence, and a CRE-reporter control vector was used to eliminate false positives. In vitro assays for positive hits were conducted. Results: A total of 23 Food and Drug Administration (FDA) and 43 Life Science Library compounds were identified, including several epidermal growth factor inhibitors and Src inhibitors. Subsequent in vitro assays confirmed that identified compounds were preferentially active in NR4A2+ cancer cells. Several candidate compounds appeared to suppress NR4A2 via inhibition of p-ERK, whereas a novel compound KU0171309 may act as a more direct inhibitor. Conclusions: Further research should focus on homologue selectivity, in vivo activity, and definitively deciphering the mechanism of action of KU0171309.

Introduction Mutations/deregulations in the phosphatidylinositol-3-kinase (PI3K) pathway are common in breast cancer, Inhibition of the PI3K pathway is recognized as a promising target for the treatment of breast cancer. Although taxanes are effective early on in advanced stage breast cancer, resistance often develops. It has been demonstrated that activation of the PI3K/AKT pathway confers resistance to paclitaxel, and in preclinical models, concomitant inhibition of the PI3K pathway enhances the efficacy of taxanes. BYL719 is a potent oral, class I PI3K inhibitor which strongly inhibits the PI3K alpha isoforms and is significantly less active against the other class I isoforms. Targeting the alpha isoform of PI3K is expected to improve the therapeutic window over inhibitors with less isoform specificity. Nab-Paclitaxel is a solvent-free, nanoparticle, albumin-based paclitaxel which takes advantage of the antitumor activity of paclitaxel while decreasing the toxicities typically associated with the solvent (Cremophor) used to administer the most common formulation of paclitaxel. Methods A 3+3 dose-escalation design evaluated three dose levels of BYL719 (250mg, 300mg, and 350mg) administered PO once daily (D1-28) with nab-Paclitaxel (100 mg/m2 intravenously D 1, 8, 15) every 28 days in patients with metastatic HER 2 negative breast cancer. The aims of the study were to 1) determine the recommended phase II dose (RPTD) of BYL719 + nab-Paclitaxel, 2) assess pharmacokinetics of BYL and nab-paclitaxel, and 3) assess preliminary efficacy. Results 10 patients were enrolled at 3 dose levels of BYL719 and 3 patients were enrolled in expansion cohort at the RPTD of BYL719 of 350 mg PO daily plus nab-paclitaxel 100mg/m2 (D 1, 8, 15). Median age was 61years; 54% (7/13) of patients were hormone receptor positive and 46% (6/13) triple negative. 85% (11/13) had visceral disease, 69% (9/13) had received prior chemotherapy for metastatic disease and 85% (11/13) had received prior taxane in adjuvant/metastatic setting. There were no DLTs in the three cohorts and the MTD of BYL was not reached. Hyperglycemia (G3:31%, G4:0%) and neutropenia (G3:15%, G4:8%), were the most common grade 3/4 adverse events. There were no Grade 3/4 diarrhea or rash. Best overall response for 12 patients was 58% (7/12) (complete response=1, partial response=6), and an additional 33% (4/12) demonstrated stable disease. Objective responses were noted in both hormone positive and triple negative disease. Median duration of response is 6.5 months (range 2-14 months). No pharmacokinetic interactions were detected when BYL and nab-paclitaxel were co-administered. Discussion: This phase I study demonstrates that combination of BYL719 and nab-paclitaxel was well tolerated and shows encouraging efficacy in metastatic HER2 negative breast cancer. Enrollment in the phase II portion of the trial at the RPTD (BYL719 350mg PO daily plus nab-paclitaxel 100mg/m2 D1,8,15 every 28 days) continues. Ongoing analysis of PI3K pathway alterations in tumor and cfDNA will be correlated with clinical response. Citation Format: Sharma P, Abramson VG, O'Dea A, Lewis S, Scott JN, Ward J, De Jong JA, Lehn C, Brown AR, Williamson SK, Perez RP, Komiya T, Godwin AK, Reed GA, Khan QJ. Safety and efficacy results from phase I study of BYL 719 plus nab-paclitaxel in HER 2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-08.

Background: Single-agent pemetrexed is a treatment for recurrent non-squamous non-small cell lung cancer (NSCLC) that provides limited benefit. Preclinical studies showed promising synergistic effects when the mammalian target of rapamycin (mTOR) inhibitor sirolimus was added to pemetrexed. Methods: This was a single-institution phase I/II study of pemetrexed in combination with sirolimus. The primary endpoint for the phase I was to determine the maximum tolerated dose (MTD) and safety of the combination. The primary endpoint for the phase II portion was to determine the overall response rate at the MTD. Key eligibility criteria included recurrent, metastatic NSCLC, ECOG performance status of 0–2, and adequate organ function. Sirolimus was administered orally daily after an initial loading dose, and pemetrexed was given intravenously on day 1 of every 21-day cycle. Results: Forty-two patients with recurrent, metastatic NSCLC were enrolled, 22 in phase I and 20 in phase II. The MTD was pemetrexed 500 mg/m2 every 3 weeks, and sirolimus 10 mg on day 1, and 3 mg daily thereafter. Treatment-related adverse events (AEs) occurred in 38 (90.5%) patients. The most common grade 3–4 treatment-related AEs were lymphopenia (31%) and hypophosphatemia (19%). Two treatment-related deaths occurred due to febrile neutropenia and infection, respectively. Among 27 total patients treated at the MTD, 6 (22.2%) had a partial response (PR), 12 (44.4%) had stable disease (SD) and 5 (18.5%) had progressive disease. Median progression-free survival (PFS) was 18.4 weeks (95% CI: 7.0–29.4). Conclusions: The combination of pemetrexed and sirolimus is active in heavily-pretreated NSCLC (ClinicalTrials.gov Identifier: NCT00923273).

Clear cell adenocarcinoma (CCA) in lung has been considered as a rare subtype of lung adenocarcinoma. However, recent classifications of lung adenocarcinoma proposed to discontinue CCA due to lack of available data with clinical significance. Patients with CCA and lung adenocarcinoma not otherwise specified (LANOS) were queried from The Surveillance, Epidemiology, and End Results Program (SEER) database. Cancer-specific survival was studied according to gender (male, female), age (0-69, 70+), SEER specific stage A system (localized, regional and distant), year of diagnosis (1973-2000, 2001-2013), surgery (yes, no), and radiation therapy (yes, no) using Kaplan-Meier curves. Multivariate analysis was used to study independent predictors of cancer-specific survival. A total of 1,227 and 233,154 patients with the diagnosis of CCA and LANOS respectively were found in the SEER database. CCA histology was significantly associated with an early year of diagnosis, younger age, early stage, surgery, and lack of radiation. Kaplan-Meier curves showed that patients with CCA histology had significantly better cancer-specific survival (P

TPS2678 Background: Checkpoint inhibitors (CPI) targeting the PD1/PD-L1 axis significantly improved patient outcomes in stage IV non-small cell lung cancer (NSCLC). However, these patients will eventually develop resistance and progression. There is a need to identify novel treatment options. Poor response to PD-L1 antibody was correlated with increase in cancer-associated fibroblasts (CAF), which is known to interact with cytotoxic T cells (CTLs) by suppressing their function in a manner similar to regulatory T cells (Tregs). Production of cytokines by CAFs leads to impaired antitumor immunity by impairing CTL function (TGF beta) and prevent recruitment/mobilization of CTLs into tumors. These effects suggesting that CAF can be a therapeutic target in lung cancer resistant to checkpoint inhibitors. Pirfenidone (P) is approved to treat pulmonary fibrosis with anti-fibrotic effect by blocking the differentiation of fibroblasts into CAFs and suppress the production of TGF beta and TGF beta-induced signaling pathways/collagens. Atezolizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets PD-L1 and inhibits the interaction between PD-L1 and its receptors, PD-1 and B7-1 (CD80), both of which function as inhibitory receptors expressed on T cells. We proposed a phase I/II trial to test the combination of atezolizumab (A) with P in patients with recurrent non-small cell lung cancer (NSCLC) after progression with CPI. The primary objective of phase I is to determine the maximum tolerated (MTD) dose of P in combination with A and assess the safety and tolerability of this combination. The secondary objective is to determine the efficacy of AP in all NSCLC participants treated in this study. Exploratory objectives include the measurement of circulating levels of TGF beta and research in expression of CAF related proteins. Methods: The initial phase I will enroll 3 patients using P at 801 mg po TID. A will be at 1200mg iv every 3 weeks. If there is ≤ 1 DLT, the study will proceed to phase II If there are 2- 3 DLT, P will be reduced to 534 mg TID. If there is ≤ 1 DLT, then this dose will proceed to phase II. If there is 2-3 DLT, then the study will be terminated. The phase II will enroll 16 patients to assess efficacy. Main inclusion criteria are patients with recurrent NSCLC after progression with first-line therapy CPI with or without chemotherapy, measurable disease, ECOG 0-2, and adequate organ function. Clinical trial information: NCT04467723.

8512 Background: KEYNOTE-799 (NCT03631784) is an ongoing study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC. Prior results from this study in a subset of pts (primary efficacy population) showed an ORR of 69.6% in cohort A (squamous and nonsquamous, n = 112) and 70.5% in cohort B (nonsquamous, n = 61), and grade ≥3 pneumonitis in 8.0% and 7.9% of pts, respectively. Here, we present results for all pts enrolled in KEYNOTE-799. Methods: This nonrandomized, multisite, open-label phase 2 trial enrolled pts aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA‒C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received 1 cycle of carboplatin AUC 6 and paclitaxel 200 mg/m2 and pembro 200 mg. After 3 wks, pts received carboplatin AUC 2 and paclitaxel 45 mg/m2 QW for 6 wks and 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2,and pembro 200 mg Q3W, and TRT in cycles 2 and 3. All pts received an additional 14 cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Efficacy and safety were assessed in all pts as-treated. Results: Of 216 pts enrolled in KEYNOTE-799 (cohort A, n = 112; cohort B, n = 104), 112 in cohort A and 102 in cohort B received treatment. As of October 28, 2020, the median (range) time from first dose to database cutoff was 18.5 (13.6–23.8) mo in cohort A and 13.7 (2.9–23.5) mo in cohort B. ORR (95% CI) was 70.5% (61.2%‒78.8%) in cohort A and 70.6% (60.7%‒79.2%) in cohort B. Median DOR was not reached in either cohort (Table). ORR was similar regardless of PD-L1 status ([TPS

e21534 Background: Patients with melanoma frequently develop central nervous system metastases. Oligometastatic disease is often treated either by surgical resection or by stereotactic radiotherapy. This study investigates the trends and clinical outcomes of patients with melanoma who have undergone surgical procedures on the central nervous system during their hospitalization. Methods: A retrospective cohort study was performed based on admissions of adult patients who underwent craniectomy/surgical resection for metastatic melanoma from 2002 -2014 using the Nationwide Inpatient Sample database. The primary outcome measure was all-cause in-hospital mortality. Secondary outcomes included length of hospital stay(LOS) and discharge disposition (home/home with health care and skilled nursing facilities/long term acute care (SNF/LTAC)). Factors associated with in-hospital mortality were examined by multivariable logistic regression. We adjusted for patient and hospital characteristics, payer, and comorbid conditions. We also examined trends of mortality for the study years. P was kept at 0.05. Results: There were an estimated 5972 discharges of patients with melanoma undergoing craniectomy/surgical resection during the study period. Patients undergoing surgical interventions were typically males (69%) and whites (79%). 98% of procedures were performed at teaching hospitals. Unadjusted all-cause in-hospital mortality was 3.1%. There was no significant difference in mortality over 13 years. Age, gender, and race were not associated with increased in-hospital mortality. Median LOS was 5 days (IQR 3-9 days). LOS was longer in elderly and those with higher Charlson co-morbid index. Of the survivors, 76% were discharged to home or with home healthcare while 24% were discharged to SNF/LTAC. Patients with age > 65 (OR 2.9; 95%CI 2.2-3.9, p < 0.001) and those with higher Charlson co-morbid index (OR 1.2; 95%CI 1.1-1.3) had higher odds for being discharged to SNF/LTAC. Conclusions: Patients who undergo craniectomy/surgical resection for melanoma have a low in-hospital mortality rate. One quarter of patients are discharged to SNF/LTAC.

e20567 Background: Prognosis of extensive-stage small cell lung cancer (ES-SCLC) remains poor. Previous randomized trials suggested consolidation chest radiation (CXRT) has a modest survival benefit; however, its role in subgroups of ES-SCLC, especially ipsilateral pleural effusion (IPE) have not been reported and unknown. Methods: Using National Cancer Database (NCDB), 283,347 ES-SCLC cases diagnosed between 2004 and 2017 were screened. Eligible cases must have been staged with 7th edition of staging system and have information about clinical T and N stage, and minimum follow-up of one month. Role of CXRT was examined in M1a, M1b, and IPE subgroups. Surveillance, Epidemiology, and End Results Program (SEER) was analyzed to independently validate our results. Univariate and multivariate analyses were conducted with Cox proportional hazard models. A p-value < 0.05 was considered as statistically significant. Results: A total of 36,762 (5,511 with M1a, 31,251 with M1b, and 2,013 with IPE) cases were analyzed. In both M1a and IPE groups, use of CXRT was significantly associated with younger age, female sex, non-academic institution, and clinical T stage. Both univariate and multivariate analyses showed that use of CXRT demonstrated significantly longer overall survival in all the groups, with lower hazard ratios in the M1a and IPE groups than in the M1b group (univariate hazard ratio 0.62, 0.56, and 0.72, respectively). Propensity score analysis of the IPE group also showed a survival advantage in the CXRT group (hazard ratio 0.54). The SEER data also showed a survival advantage of CXRT in the IPE group (univariate hazard ratio of 0.40). Conclusions: This retrospective database analysis suggests M1a and in particular IPE subgroups have more survival benefit of CXRT than the M1b subgroup. Further studies are warranted to confirm the hypothesis.

e18021 Background: The care of hospitalized head and neck cancer patients often involves a multidisciplinary approach. The trends, outcomes and disposition in hospitalized patients with head and neck cancer in United States for the past two decades has not been well characterized. This retrospective study involves analysis of the demographics, outcomes and disposition of these patients and their trend over 15 years. The presence of medical comorbidities and the relationship to inpatient mortality was also studied. Methods: Hospitalization data from the National Inpatient Sample database was analyzed for the years: 2000 to 2014. Patients with head and neck cancer were identified using ICD-9 codes. Demographic features such as age, gender, race, geographical location, hospital size, hospital location, insurance etc. were analyzed. The trend of mortality was analyzed for the study period of 15 years. A sub-analysis of associated comorbidities was also performed in patients who have died during hospitalization. Univariate analysis was initially performed followed by multivariate analysis and logistic regression to identify risk factors associated with mortality. Results: An estimated 145,262 hospitalizations involving patients with head and neck cancer from 2000 to 2014 were studied and it showed a gradual yearly increment in hospitalization. 41% of the hospitalizations were in the 50-64 years age group. There was a 2:1 male preponderance. Caucasians constituted 60% followed by African Americans at 10%. A majority of the hospitalizations occurred in large sized hospitals and urban teaching hospitals. The mean length of stay was 6.4 days but 38% of the hospitalizations involving 2-5 days of stay. The inpatient mortality rate was 4.6% and it down trended over the past 15 years with statistical significance (p < 0.05). Inpatient mortality was highest in the > 80 years age group. Of note, inpatient mortality was equal between both the genders. Mortality was highest in the groups with a length of stay below 2 days and above 11 days. 58% of the discharges did not need any special services while 21% of the discharges involved home health care. The most common comorbidities were smoking and hypertension while < 1% of morbid obesity was observed. Multivariate analysis showed malnutrition, ESRD, cirrhosis, stroke and CHF were significant risk factors (ORs: 1.6, 1.94, 2.18, 2.2 and 1.78 respectively). Conclusions: Mortality in hospitalized patients with head and neck cancer has improved over the past 15 years. Inpatient mortality was high in the very elderly and in female patients (compared to the male preponderance upon admission). Malnutrition, cardiac/liver/renal dysfunction and stroke were significant risk factors for inpatient mortality. Strategies to mitigate inpatient mortality in these patients need to factor the above risk factors during their in-hospital management.

To elucidate the origins of the endemic fish of Lake Biwa, an ancient lake in Japan, and the role of the lake in the diversification of freshwater fish in western Japan, we established a molecular phylogenetic framework with an absolute time scale and inferred the historical demography of a large set of fish species in and around the lake. We used mtDNA sequences obtained from a total of 190 specimens, including 11 endemic species of Lake Biwa and their related species, for phylogenetic analyses with divergence time estimations and from a total of 2319 specimens of 42 species (including 14 endemics) occurring in the lake for population genetic analyses. Phylogenetic analysis suggested that some of the endemic species diverged from their closest relatives earlier (1.3–13.0 Ma) than the period in which the present environmental characteristics of the lake started to develop (ca. 0.4 Ma), whereas others diverged more recently (after 0.4 Ma). In contrast, historical demographic parameters suggested that almost all species, including endemic and nonendemic ones, expanded their populations after the development of the present lake environment. In phylogeographic analyses, common or very close haplotypes of some species were obtained from Lake Biwa and other regions of western Japan. The phylogenetic and historical demographic evidence suggests that there was a time lag between phylogenetic divergence and population establishment and that phenotypic adaptation of some endemic species to the limnetic environment occurred much later than the divergences of those endemic lineages. Population structure and phylogeographic patterns suggest that Lake Biwa has functioned not only as the center of adaptive evolution but also as a reservoir for fish diversity in western Japan.

Introduction Mucoepidermoid carcinoma (MEC) primarily occurs in salivary glands, but can also arise in other organs; however, the impact of primary location on patient prognosis is largely unknown. Methods Using Surveillance, Epidemiology and End Results Program (SEER) data we investigated whether the clinical and prognostic features of MEC differed among multiple organ sites. The SEER-18 dataset from 18 cancer registries in the US between 1972 and 2012 was chosen. The common organ sites with 100 or more cases were further analyzed. Survival analysis included Log-rank tests of Kaplan–Meier curves and univariate/multivariate proportional hazard analysis. Results A total of 7,191 MEC cases with survival data were identified in the SEER data. Major salivary gland (MSG) was the primary site in 52.9% of cases, followed by gum and other mouth (23.6%), lung (5.9%), tongue (3.4%) and others. Compared to MSG-MEC, primary lung MEC had significantly more patients with age

Background: Although randomized trials demonstrated survival benefit of adjuvant chemotherapy, previous reports have suggested that its use in elderly populations for early stage non-small cell lung cancer (NSCLC) was infrequent. Oncologists often hesitate to offer adjuvant chemotherapy in resected early stage non-small cell lung cancer for elderly population. The status of adjuvant chemotherapy in this population is unknown for recent decades. Materials and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database which represents about 28% of the US population, we examined the incidence of chemotherapy in resected stage II-III NSCLC between 2004 and 2015. Staging was determined according to the American Joint Committee on Cancer (AJCC) 6th version. Cases were grouped by age (20-69, 70-79, and 80+). Trends in use of chemotherapy by age group was assessed by univariate and multivariate analyses. Results: A total of 35,009 were selected as surgically resected stage II-III NSCLC. Use of chemotherapy was 66.9%, 48.2%, 25.0% in age 20-69, 70-79, 80+, respectively. Multivariate analysis demonstrated that younger age (20-69) and recent year (2010-2015) of diagnosis were associated with increased use of chemotherapy. Chemotherapy use increased from 2004 to 2015 by 11.0%, 18.3%, and 11.3% in age 20-69, 70-79, 80+, respectively. In the age 70-79 group, increased use of chemotherapy was greater in stage II (24.3%) than stage III (14.1%). Five-year overall survival in age 70-79 group mildly increased by 7.6% from 2004 to 2011. Conclusion: This study suggests that use of adjuvant chemotherapy in elderly population increased primarily in age 70-79. Few patients in age 80+ receive adjuvant chemotherapy even in recent years. This study not only informs oncologists of current status but also suggests further research on very elderly populations. Citation Format: Takefumi Komiya, Emily Powell, Achuta Kumar Guddati. Recent trends in use of adjuvant chemotherapy in elderly stage II-III non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2028.

9060 Background: Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined. Methods: Using National Cancer Database (NCDB), Stage IV LCNEC cases diagnosed in 2014-2016 with at least 30-day follow up were analyzed. Clinical demographics included age (20-69 vs. 70+), sex (male vs. female), race (whites vs. others), insurance (uninsured vs. others), institution (academic vs. others), Charlson-Deyo score (0-1 vs. 2-3), brain metastasis (Yes vs. No), liver metastasis (Yes vs. No). Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion (Yes vs. No), radiation (Yes vs. No), chemotherapy (Yes vs. No), and immunotherapy (Yes vs. No). Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analyses. A two-sided p-value < 0.05 was considered as significant. Results: Among 661 eligible cases, 37 patients were treated with immunotherapy. No significant association between use of immunotherapy and clinical demographics was observed except for use of chemotherapy (p = 0.0008). Chemotherapy was administered in 34 (92%) and 406 (65%) of cases in immunotherapy and non-immunotherapy groups, respectively. Use of immunotherapy was associated with improved overall survival (Log-rank p = 0.0168). Landmark analysis in the immunotherapy group showed 12 and 18-month survival of 34.0% and 29.1%, respectively, as compared with 24.1% and 15.0% in the non-immunotherapy group Multivariate analysis demonstrated that female sex, presence of liver metastases, surgery, use of chemotherapy and immunotherapy (HR = 0.64, p = 0.0164) had significantly improved survival. Propensity score matching in overall survival showed a nonsignificant trend (p = 0.0733) in favor of immunotherapy group. Conclusions: This retrospective study using one of the largest cancer databases suggests that use of immunotherapy may improve survival of LCNEC patients. Prospective studies are warranted for further validation.

e18570 Background: Well-differentiated thyroid cancer has better outcomes compared to anaplastic thyroid cancer. The incidence of well-differentiated thyroid cancer is higher in women whereas it is approximately the same in both genders for anaplastic thyroid cancer. The variability of incidence-based mortality across gender in the context of race has not been studied. This study analyzes the rates of incidence-based mortality among both the genders in four racial groups. Methods: The Surveillance, Epidemiology, and End Results Database was queried to conduct a nation-wide analysis for the years 2000 to 2016. Incidence-based mortality for all stages of well-differentiated and undifferentiated thyroid cancer was queried and the results were grouped by race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander) and gender. All stages and ages were included in the analysis. T-test was used to determine statistically significant difference between various subgroups. Results: Incidence-based mortality rates (per 100000) for well-differentiated and undifferentiated thyroid cancer for all races and both the genders are shown in the table below. The incidence-based mortality rates for both genders is approximately the same despite a 2-3:1 difference in incidence. Anaplastic thyroid cancer has a higher mortality rate in Caucasian and Asian/pacific Islander women compared to men despite an equal ratio of incidence. As expected, the mortality rates of anaplastic thyroid cancer were significantly higher compared to well-differentiated cancer across all races and genders. Also, Asian/Pacific Islander women have a higher rate of mortality compared to both the genders of Caucasian and African American races. Conclusions: Incidence-based mortality for anaplastic thyroid cancer is higher in women in all races whereas there is no difference in mortality between men and women for well-differentiated thyroid cancer. This is divergent from the incidence ratios noted in these malignancies. In the context of increasing incidence of thyroid cancer for the past few decades, this data suggests that additional resources may be devoted to decreasing the disparity of mortality in this gender. [Table: see text]

e14096 Background: Patients with human immunodeficiency virus (HIV) and history of prior malignancy have been historically excluded from clinical trials. In late 2017, ASCO and Friends of Cancer Research proposed to include patients with HIV and history of prior malignancy for which treatment has been completed for at least 2 years. We aimed to determine if these recommendations were followed. Methods: Using clinicaltrials.gov, we performed a systematic review of immunotherapy trials involving pembrolizumab, nivolumab, avelumab, atezolizumab, and durvalumab. We included all solid tumor trials in patients aged 18 years and older performed between January 1, 2016 and December 31, 2019. The following data were recorded for each trial: study period (2016-17 vs. 2018-19), drug type (pembrolizumab vs other), inclusion of HIV positive population (yes or no), and inclusion of prior malignancy per guidelines (yes or no). A Chi-square analysis was performed on the two study periods in relation to HIV status and history of prior malignancy. The same analysis was also performed on HIV status/ history of prior malignancy in relation to the drug type. Significance was set at p-value < 0.05. Results: A total of 305 studies reached final analysis, of which 123 involved pembrolizumab. For all drugs combined, there was no significant change in the two study periods in the inclusion of HIV patients (p = 0.48) or history of prior malignancy (p = 0.68). A subanalysis of the pembrolizumab trials showed a statistically significant inclusion of history of prior malignancy compared to other drugs in the entire study period of 2016-2019 (p = 0.03), but this did not hold true for HIV status (p = 0.69). Conclusions: Our study suggests that recent recommendations by ASCO and Friends of Cancer Research regarding HIV status and history of prior malignancy are not being followed. This could be due to limited awareness surrounding the recommendations or continued fears regarding treatment-related adverse events in this subset of patients. [Table: see text]

e16597 Background: Most patients with cholangiocarcinoma have non resectable disease at the time of diagnosis and usually die within 6-12 months. The 5-year survival rate is very low (about 5%), and since most patients present with advanced disease at time of diagnosis, treatment includes chemoradiation and biliary stenting. Recently, trials with immunotherapy (IO) for treatment of advanced cancer have shown promising results as alternative therapeutic options. Despite indications in other solid tumors, the role of IO is unknown for biliary cancer. Methods: Using National Cancer Database (NCDB), cases of Stage IV biliary cancers (including gallbladder and cholangiocarcinoma) diagnosed in the period of 2014-2016 with at least 30-day follow up were analyzed. The following clinical demographics were included: age (younger than 70 vs. older than 70), sex (male vs. female), race (whites vs. others), insurance (uninsured vs. insured), liver metastasis (Yes vs. No). We also analyzed data regarding cancer treatment, including radiation (Yes vs. No), chemotherapy (Yes vs. No), and IO (Yes vs. No). Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. A p-value < 0.05 was considered significant. Results: Among 6,344 eligible cases, 57 patients were treated with IO. No significant association between use of IO and clinical demographics was observed except for use of chemotherapy (p = 0.001) and primary location (gallbladder vs. others, p = 0.042). Chemotherapy was administered in 52 (91%) and 4112 (65%) of cases in IO and non-IO groups, respectively. Use of IO was associated with improved overall survival in both univariate and multivariate analyses (p = 0.0005and 0.0156, respectively). Median overall survival (in months) was 14.0 in the IO group vs 7.0 in the non-IO group. Landmark analysis in the IO group showed 12 and 24-month survival of 56.1% and 19.3% respectively, as compared with 27.8% and 7.6% in the non-IO group. Conclusions: This retrospective data analysis using a large cancer database suggests that use of IO could improve survival in patients with advanced biliary cancer. More studies will be needed in the future to validate these results.

9026 Background: Occult (T0) primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Its prognosis has not been evaluated well in the literature. Methods: Using National Cancer Database (NCDB), cases diagnosed between 2004 and 2016 with unresectable clinical stage III NSCLC with N2 or N3 involvement were selected and assigned to T0 or T1-4 group according to AJCC staging version 6th or 7th. Clinical demographics including use of chemotherapy/immunotherapy in first course of treatment were collected. As validation, independent data using Surveillance, Epidemiology, and End Results Program (SEER) was analyzed accordingly. Survival analyses were conducted using Kaplan-Meier and log-rank tests. Results: A total of 458 and 84,263 cases met criteria for unresectable, N2/N3 stage III NSCLC with T0 and T1-4 status, respectively. T0 status was associated with younger age, recent diagnosis, adenocarcinoma histology, N3, and use of chemotherapy. Overall survival (OS) was improved in T0 over T1-4 group (p < 0.0001) with a five-year survival rate of 30.5% and 12.7%, respectively, with a validation with multivariate proportional hazard models. Propensity score matching analyses using all 458 patients in each group demonstrated a significant difference in OS (p < 0.0001). The difference was also significant in a subset of those who have undergone chemoradiation (p < 0.0001). Independent analysis using SEER data confirmed its superior survival of T0 over T1-4 with a five-year survival rate of 35.3% and 13.5%, respectively. Conclusions: Both NCDB and SEER analyses demonstrated better survival of T0 than T1-4 counterpart in the setting of unresectable stage III NSCLC, irrespective of chemotherapy status. This group may require a distinct assignment to new staging group after further investigation.