The Clinical Role of Adjuvant Chemotherapy after Sublobar Resection for Non-Small-Cell Lung Cancer ≤ 20 mm with Lymph Node Metastases: A Propensity-Matched Analysis of the National Cancer Database.

Sublobar resection is a standard surgical procedure for small-sized non-small-cell lung cancer (NSCLC). However, the clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. The National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. The Kaplan-Meier method with a log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. The samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

Impact of Liver Metastasis on First-Line Immunotherapy in Stage IV Non-Small Cell Lung Cancer.

Background: Immunotherapy has become a key component of systemic therapy in stage IV non-small cell lung cancer (NSCLC). However, there have been conflicting reports of its efficacy in patients with liver metastasis (LM). Methods: Using National Cancer Database (NCDB), patients who have been diagnosed and treated at Commission on Cancer- participating US institutions were screened for analysis. Selection criteria included clinical stage IV NSCLC, available cTNM stage information, overall survival (OS) with at least 1 month, and diagnosis between 2015 and 2017. They were grouped based on status of LM as well as use of immunotherapy. Clinical characteristics were collected and their association with LM/immunotherapy was analyzed. Impact of immunotherapy on OS was examined according to LM status. Propensity score matching (PSM) analysis was also conducted. Results: A total of 83,479 including 18,497 LM-positive and 64,982 LM-negative patients met the study criteria. Presence of LM was associated with a number of clinical variables such as younger age, male sex, and chemotherapy. OS in patients with LM was significantly worse than that in those without LM (median OS, 5.0 vs. 8.8 months; hazard ratio (HR), 1.46; log-rank, P < 0.0001). Significant OS benefit from immunotherapy was observed in both LM-positive (median OS, 4.1 vs. 9.0 months; HR, 0.62; P < 0.0001) and negative groups (median OS, 7.2 vs. 15.6 months; HR, 0.64; P < 0.0001). Conclusion: Immunotherapy benefited similarly to the survival of metastatic NSCLC patients regardless of with or without LM. Further research to validate the result would be warranted.

Efficacy of immune checkpoint inhibitors in younger patients with non-small cell lung cancer.

PURPOSE: Because patients younger than 40 years are rarely enrolled in clinical trials in non-small cell lung cancer (NSCLC), their survival benefit of immune checkpoint inhibitors (ICIs) needs to be clarified. METHODS: The National Cancer Database was queried for patients who were diagnosed with stage IV NSCLC between 2016 and 2018. ICIs were administered in the first-line setting. The overall survival (OS) of patients with stage IV NSCLC according to the receipt of ICIs was compared in different age groups (< 40, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years). Multivariate analyses identified the clinical characteristics predictive of OS. Propensity score matching (PSM) was conducted to reduce the biases arising from clinical characteristics. RESULTS: This study included 126,476 patients with stage IV NSCLC. In univariate analysis, ICI treatment was not associated with a survival benefit in patients younger than 40 years with stage IV NSCLC relative to their ICI-naïve counterparts after PSM (median OS: 24.2 months vs. 24.0 months, hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.81-1.27, P = 0.9031). Multivariate analysis revealed that ICI use was not an independent predictor of OS in patients with stage IV NSCLC < 40 years old (HR = 0.96, 95% CI = 0.76-1.21, P = 0.7230). Sequential improvement of the HR was observed with increasing age. CONCLUSION: Our study suggested a poor survival benefit of ICIs in stage IV NSCLC patients younger than 40 years old, which should be validated in prospective studies.

Exclusion of Patients with Autoimmune Disease in Lung Cancer Clinical Trials.

BACKGROUND: The exclusion of patients with autoimmune disease has been a topic of cancer immunotherapy trial. This study aims to find recent trends in exclusion of autoimmune disease. METHODS: Using the website clinicaltrials.gov, we searched for clinical trials that were initiated in 2012 or later and enrolled patients with lung cancer who were treated with PD-1/PD-L1 therapy. Only trials including US locations were analyzed. RESULTS: A total of 198 trials met screening criteria in this study. There were 68 trials which had complete exclusion of any autoimmune disease in patients. In addition, 13 trials excluded active autoimmune disease and 87 trials excluded active autoimmune disease requiring treatment. The remaining 37 trials had undefined exclusion.  Studies that had larger enrollment of patients with autoimmune diseases were largely in industry. The complete exclusion of patients with autoimmune diseases has decreased recently. CONCLUSION: Exclusion of patients with active autoimmune disease requiring treatment was one of the common exclusion criteria found.  Strict exclusion of patients with autoimmune diseases has been decreasing over the years.

Lymph node dissections and survival in sublobar resection of non-small cell lung cancer ≤ 20 mm.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Performing ≥ 10 LNDs has a prognostic role in patients with small-sized NSCLC even if the resection is sublobar.

Clinical impact of number of lymph nodes dissected on postoperative survival in node-negative small cell lung cancer.

Objectives: Small cell lung cancer (SCLC) is a lethal histologic subtype of lung cancer. Although the Commission on Cancer recommends pathological examination of at least 10 lymph nodes dissected (LNDs) for resected early-stage non-small cell lung cancer, its survival benefit of LNDs in patients with early-stage SCLC is unknown. Methods: The National Cancer Database was queried for SCLC patients with clinical stage I-II and clinical N0, NX disease per AJCC 7th edition who had undergone lobectomy between 2004 and 2017. Overall survival of SCLC patients by the number of LNDs was compared using Log-rank tests. Univariate and multivariable Cox proportional hazards analyses were performed. Results: In total, 688 (42%), 311 (20%), 247 (16%), 196 (12%), 126 (8%), and 36 (2%) of 1,584 patients with early-stage SCLC had ≥10, 7-9, 5-6, 3-4, 1-2, and 0 LNDs, respectively. The sequential improvement in the HRs was no longer evident if the number of LNDs exceeds 4. Patients with ≥3 LNDs (n = 1,422) had a significantly longer overall survival than those with <3 LNDs (n = 162) (hazard ratio for death: 0.76, 95% confidence interval: 0.62-0.94, P = 0.0087). Multivariate analysis revealed that ≥3 LNDs was an independent factor for predicting overall survival (hazard ratio for death: 0.76, 95% confidence interval: 0.61-0.93, P = 0.0083). Conclusions: Although we are reluctant to recommend a definitive "optimal number" of LNDs, our findings suggest the prognostic and therapeutic roles for performing ≥3 LNDs in patients with early-stage SCLC who undergo lobectomy.

Adjuvant radiation therapy improves survival in stage IIIA (N2) non-small cell lung cancer with persistent N2 disease after neoadjuvant chemotherapy.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Advances in the Treatment of Mucoepidermoid Carcinoma.

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 CDKN2A, TP53, CDKN2B, BAP1, etc. These mutations are involved in the transformation of low-grade tumors to high-grade tumors, presenting a vital tool for evaluating the aggressive behavior of this carcinoma. Detailed immunohistochemical and translocation studies can help develop targeted therapies and monitor treatment response. Therefore, biomarker-driven research will immensely improve the outcome, especially in advanced cases. Based on thorough histology and chromosomal translocations, a more personalized treatment plan can improve the overall disease outcome. The purpose of this article is to elaborate on the current treatment advancements, particularly chemotherapy and targeted therapy, as an effective treatment modality for the management of MEC and highlight the comparison with traditional treatment approaches.

Induction Immunotherapy Followed by Thoracic Radiation without Chemotherapy in Unresectable Stage III Non-Small Cell Lung Cancer: A Case Series.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prognostic impact of chronological age on efficacy of immune checkpoint inhibitors in non-small-cell lung cancer: Real-world data from 86 173 patients.

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 <75 years. Patients aged ≥75 years treated with ICIs had significantly longer OS than those not treated with ICIs (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.58-0.64, p < 0.0001). The corresponding HR in patients aged <75 years was 0.67 (95% CI 0.65-0.68, p < 0.0001). Cox modeling confirmed the survival benefit of ICI therapy in patients aged ≥75 years (HR for patients not receiving ICIs 1.63 [95% CI: 1.55-1.71], p < 0.0001). The corresponding HR in patients aged <75 years was 1.47 (95% CI 1.43-1.51, p < 0.0001). Chronological age does not appear to negatively impact the survival benefit of ICI therapy in patients with stage IV NSCLC according to this large real-world database analysis.

Prognostic Impact of Single and Multiple Descriptors in Pathologically Staged T3N0M0 NSCLC.

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.

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial.

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/m2), and pembrolizumab (200 mg), followed by carboplatin (AUC 2 mg/mL/min) and paclitaxel (45 mg/m2) 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/m2), pemetrexed (500 mg/m2), 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.

Role of thoracic radiation in extensive stage small cell lung cancer: a NCDB analysis.

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 < 0.05 was considered as statistically significant. A total of 36,762 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 M1a and IPE groups than M1b (univariate hazard ratio 0.62, 0.56, and 0.72, respectively). Propensity score analysis of IPE group showed the survival advantage with hazard ratio of 0.54. Use of SEER data validated its survival advantage of CXRT in IPE group. This retrospective database analysis suggests M1a and IPE subgroups have more survival benefit of CXRT than M1b subgroup. Further studies are warranted to confirm the hypothesis.

Role of Immunotherapy in Stage IV Large Cell Neuroendocrine Carcinoma of the Lung.

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 <0.0001) use of chemotherapy (HR= 0.44, p <0.0001), and use of immunotherapy (HR=0.64, p=0.0164) had statistical significance. Propensity score matching in overall survival analysis showed a nonsignificant trend (p=0.0733) in favor of immunotherapy treatment. CONCLUSION: This retrospective study using NCDB suggests that use of immunotherapy may improve survival of LCNEC patients.

Survival benefit from immunocheckpoint inhibitors in stage IV non-small cell lung cancer patients with brain metastases: A National Cancer Database propensity-matched analysis.

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 < 0.0001). Multivariable Cox modeling after propensity score matching confirmed the survival benefit from ICI for stage IV NSCLC patients with BMs (HR: 0.75, 95% CI: 0.67-0.83, p < 0.0001). The HR in NSCLC patients without BMs treated with ICI compared with those without ICI was 0.77 (95% CI: 0.73-0.82, p < 0.0001). Survival in stage IV NSCLC patients with BMs was significantly improved by ICI treatment at levels comparable to those without BMs using a retrospective database. ICI may be one of the promising treatment options for stage IV NSCLC patients with BMs. These findings should be validated in future prospective studies.

Impact of immunotherapy use in patients with stage IV pancreatic carcinoma.

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 <0.05 was considered significant. RESULTS: Among 25,596 eligible cases, 163 patients were treated with IO. A significant association between the use of IO and several clinical demographics (age <70, academic institution, adenocarcinoma, lung metastasis, radiation, chemotherapy) was noted. Chemotherapy was administered in 133 (82%) and 16,342 (64%) of cases in the IO and non-IO groups, respectively. Use of IO was associated with improved overall survival (OS) in both univariate and multivariate analyses (P<0.0001 for each). Median OS (in months) was 12.2 in the IO group vs. 5.8 in the non-IO group. Landmark analysis in the IO group showed 12 and 24-month survival of 51.0% and 20.0% respectively, as compared with 28.2% and 11.9% in the non-IO group. Propensity score matching analysis also demonstrated a trend toward improved OS in IO group (P=0.0753). Median survival was 12.2 and 8.9 months, respectively. CONCLUSIONS: This retrospective data analysis using a large cancer database suggests that use of IO could improve survival in patients with advanced pancreatic cancer. More studies will be needed in the future to validate these results.

Recent trends in use of adjuvant chemotherapy in elderly stage II-III non-small cell lung cancer.

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.

Difference of environment behind research and clinical practice between USA and Japan.

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.

Role of T0 status in overall survival for unresectable stage III non-small cell lung cancer: A NCDB analysis.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.