Lung Cancer Survival Trends in the Veterans Health Administration.

INTRODUCTION: Lung cancer survival is improving in the United States. We investigated whether there was a similar trend within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States. MATERIALS AND METHODS: Data from the Veterans Affairs Central Cancer Registry were analyzed for temporal survival trends using Kaplan-Meier estimates and linear regression. RESULTS: A total number of 54,922 Veterans were identified with lung cancer diagnosed from 2010 to 2017. Histologies were classified as non-small-cell lung cancer (NSCLC) (64.2%), small cell lung cancer (SCLC) (12.9%), and 'other' (22.9%). The proportion with stage I increased from 18.1% to 30.4%, while stage IV decreased from 38.9% to 34.6% (both P < .001). The 3-year overall survival (OS) improved for stage I (58.6% to 68.4%, P < .001), stage II (35.5% to 48.4%, P < .001), stage III (18.7% to 29.4%, P < .001), and stage IV (3.4% to 7.8%, P < .001). For NSCLC, the median OS increased from 12 to 21 months (P < .001), and the 3-year OS increased from 24.1% to 38.3% (P < .001). For SCLC, the median OS remained unchanged (8 to 9 months, P = .10), while the 3-year OS increased from 9.1% to 12.3% (P = .014). Compared to White Veterans, Black Veterans with NSCLC had similar OS (P = .81), and those with SCLC had higher OS (P = .003). CONCLUSION: Lung cancer survival is improving within the VHA. Compared to White Veterans, Black Veterans had similar or higher survival rates. The observed racial equity in outcomes within a geographically and socioeconomically diverse population warrants further investigation to better understand and replicate this achievement in other healthcare systems.

A retrospective study on the effect of Chinese patent medicine combined with conventional treatment on the survival outcomes of 313 patients with stage II-III NSCLC.

PURPOSE: We aim to explore the effect of Chinese Patent Medicine (CPM), including Huisheng oral solution (HSOS) on the 4-year survival rate of patients with stage II and III non-small cell lung cancer, and assess the association between blood coagulation indicators and survival outcomes. MATERIALS AND METHODS: 313 patients diagnosed with stage II and III NSCLC were collected during 2015-2016. Kaplan-Meier method and Cox proportional hazard model were applied to analyze the factors affecting the 4-year survival rate of patients. RESULTS: According to the effect of CPM, the medicine prescribed in this study could be classified into two types. The proportion of patients who received "Fuzheng Quyu" CPM for more than three months was higher than the proportion of patients who received other two types of CPM for more than three months. Medical records of 313 patients with NSCLC were analyzed. 4-year survival rate for patients received CPM more than 6 months and 3 months were higher than those received CPM less than 3 months (P = 0.028 and P = 0.021 respectively. In addition, 4-year survival rate for patients who received HSOS for more than 3 months was higher than those who received HSOS for less than 3 months (P = 0.041). Patients with elevated preoperative fibrinogen (FIB) level and those without surgery had an increased mortality risk (HR = 1.98, P < 0.01, and HR = 2.76, P < 0.01 respectively). CONCLUSION: The medium and long-term use of CPM/HSOS was positively associated with higher survival rate in NSCLC patients. Patients with high-level preoperative FIB level and those without surgery might have a poor prognosis in the following years.

Comparing the Efficacy of Video-Assisted Thoracoscopic Surgery and Open Thoracotomy in Sleeve Lobectomy for the Treatment of Central-Type Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Objective: Central-type Non-small Cell Lung Cancer (NSCLC) treatment involves different surgical techniques, including Video-Assisted Thoracoscopic Surgery (VATS) and Open Thoracotomy Sleeve Lobectomy. However, there remains a lack of consensus on the most effective treatment modality. Methods: This study strictly adhered to PRISMA guidelines. Four electronic databases were searched without time or language limitation, and studies comparing VATS and Open Thoracotomy in patients with central-type NSCLC undergoing sleeve lobectomy were included. Primary outcomes were perioperative outcomes (blood loss, operation time, intraoperative lymph node dissection count, postoperative hospital stay, and complication rates), 3-year Progression-Free Survival (PFS) rate, and Overall Survival (OS) rate. Results: The meta-analysis included six studies with 569 patients. VATS was associated with longer operation time [SMD = 0.75, 95% CI (0.29, 1.21)], less intraoperative blood loss [SMD = -0.23; 95% CI (-0.44, -0.01)], and shorter hospital stay [SMD = -0.53; 95% CI (-0.73, -0.34)]. There were no significant differences in the number of lymph nodes dissected, postoperative complications, and 3-year PFS and OS rates between the two groups. Conclusions: VATS sleeve lobectomy for central-type NSCLC results in less surgical trauma and quicker postoperative recovery without adversely impacting tumor prognosis compared to open thoracotomy sleeve lobectomy. Despite a longer operation time, VATS could be considered an alternative to open thoracotomy sleeve lobectomy. VATS sleeve lobectomy is a safe and effective alternative to open thoracotomy in treating central-type NSCLC, as it results in less surgical trauma and quicker postoperative recovery without impacting tumor prognosis negatively. More well-designed randomized controlled trials are required to verify these findings.

Establishment and Validation of a Survival Benefit Prediction Model for Non-small Cell Lung Cancer after Immunotherapy.

Objective: This study aimed to analyze the prognosis of patients with non-small cell lung cancer (NSCLC) after receiving immunotherapy and construct a prediction model to evaluate the overall survival rate of patients. Methods: This study was a retrospective study that collected data from 493 NSCLC patients who received immunotherapy for the first time. Survival data were analyzed using Cox regression models and the Kaplan-Meier method. The average age of patients was 56 years, and the data collection process included regular outpatient follow-up and observation of overall survival (OS) in the last 36 months. Results: Multivariate analysis identified significant risk factors such as smoking history, age, T stage, and M stage on survival and disease progression. The model's performance indicators (C-index and AUC) and calibration curve verified the model's accuracy and predictive ability. In the training set, the AUCs of 3-year and 5-year survival were 0.761 and 0.763, respectively, and in the validation set, they were 0.739 and 0.761. Conclusion: This study developed a prediction model for evaluating the survival of NSCLC patients after immunotherapy that integrates multiple influencing factors. This predictive model can be used as a tool to assess individual risks in NSCLC patients after immunotherapy, helping clinicians to develop more precise treatment and follow-up plans, potentially improving patient outcomes.

Utilizing Bioinformatics Technology to Explore the Potential Mechanism of Danggui Buxue Decoction against NSCLC.

While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients (p < 0.05). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.

Effect of thoracic surgery regionalization on long-term survival after lung cancer resection.

OBJECTIVE: Existing evidence demonstrates some benefit of regionalization on early postoperative outcomes following lung cancer resection, but data regarding the persistence of this effect in long-term mortality are lacking. We investigated whether previously reported improvements in short-term outcomes translated to long-term survival benefit. METHODS: We retrospectively reviewed patients undergoing major pulmonary resection (lobectomy, bilobectomy, or pneumonectomy) for cancer within our integrated health care system before (2011-2013; n = 782) and after (2015-2017; n = 845) thoracic surgery regionalization. Overall survival was compared by Kaplan-Meier analysis, and 1- and 3-year mortality was compared by the by χ2 or Fisher exact test. Multivariable Cox regression models evaluated the effect of regionalization on mortality adjusted for relevant factors. RESULTS: Kaplan-Meier curves showed that overall survival was better among patients undergoing surgery postregionalization (log-rank test, P < .0001). Both 1- and 3-year mortality were decreased after regionalization: to 5.7% from 11.1% (P < .0001) for 1 year and to 17.0% from 25.5% (P = .0002) for 3 years. The multivariable adjusted Cox regression analysis revealed that only regionalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.42-0.76), age (HR, 1.03; 95% CI, 1.02-1.04), cancer stage (HR, 1.72, 1.83, and 2.56 for stages II, III, and IV, respectively), and Charlson comorbidity index (HR, 1.80 for 1-2; 2.05 for ≥3) were independent predictors of mortality. CONCLUSIONS: We found that overall mortality as well as 1- and 3-year mortality for lung cancer resection were lower after thoracic surgery regionalization. The association between regionalization and reduced mortality was significant even after adjusting for other related factors in a multivariable Cox analysis. Notably, surgeon volume, facility volume, surgeon specialty, neoadjuvant treatment, and video-assisted thoracoscopic surgery approach did not significantly affect mortality in the adjusted model.

LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. METHODS: Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. RESULT: Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting ß-TrCP1 mediated ubiquitin degradation of ß-catenin proteins, which in turn causes enhanced tumorigenesis. CONCLUSIONS: Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.

The association of aspirin use with overall survival of patients with inoperable non-small cell lung cancer: a retrospective study.

BACKGROUND: Studies have indicated that individuals taking aspirin have a reduced risk of cancers and have also established chemo-preventive benefit of aspirin in colorectal cancer. However, research on the association between aspirin use and the survival in patients with lung cancer has revealed inconsistent results. In this study, we investigated the effect of aspirin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients. METHODS: We identified a cohort of 38,842 patients diagnosed with NSCLC between 2000 and 2012 using the Taiwan's National Health Insurance Research Database and used propensity score matching to reduce possible confounding factors. In total, 9864 patients (4932 matched pairs) were included in the matched cohort. Aspirin exposure was analyzed to identify a possible association with mortality in patients with inoperable NSCLC. Time-dependent Cox regression models were used to calculate the hazard ratios (HRs) and the 95% confidence intervals (95% CIs) that corresponded with aspirin exposure. RESULTS: A total of 4979 patients used aspirin at the time of diagnosis of NSCLC. The median overall survival (OS) of the aspirin users was 1.73 (interquartile range, 0.94-3.53) years compared with the 1.30 (interquartile range, 0.69-2.62) years of the non-aspirin users. The Cox proportional hazard model with the time-dependent covariate revealed that aspirin use was associated with a significantly longer OS (HR: 0.83, 95.0% CI: 0.80-0.86). After controlling the sociodemographic characteristics (age, sex, income, and level of urbanization) and lung cancer treatments by propensity score matching, the aspirin users still had a significantly longer OS than the non-aspirin users (HR: 0.79, 95.0% CI: 0.75-0.83). CONCLUSION: Aspirin use is associated with a longer OS in patients with inoperable NSCLC, suggesting that aspirin has a potential anticancer effect. These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients.

Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.

Efficacy of ginseng and its ingredients as adjuvants to chemotherapy in non-small cell lung cancer.

Chemotherapy is applied to treat non-small cell lung cancer (NSCLC), but often limited due to its unstable therapeutic effects and adverse reactions (ADRs). Ginseng and its main ingredients (ginsenosides and polysaccharides) have been clinically used as adjuvants to chemotherapy. However, their efficacies were based on individual trials with relatively small sample sizes, and it is difficult to draw a valid conclusion. In this study, eligible randomized controlled trials (RCTs) were searched in six international and Chinese databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Wanfang). The outcomes of the objective response rate (ORR), disease control rate (DCR), ADRs, quality of life (QOL), survival rates and immunity were extracted using standard data extraction forms. The efficacies of ginseng and its ingredients as adjuvants to chemotherapy in NSCLC were investigated and compared by meta-analysis and subgroup meta-analysis, respectively. A total of 28 RCTs including 2503 subjects were enrolled, and most of the eligible studies were of low-to-moderate quality. For the evaluation of ginseng and its ingredients as adjuvants to chemotherapy, the risk ratio (RR) or standardized mean difference (SMD) and 95% confidence intervals (CI) of the ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, nausea and vomiting, diarrhea, CD4+/CD8+ and one- and two-year survival rates, and QOL were 1.35 (1.21,1.50), 1.20 (1.14,1.28), 0.59 (0.50, 0.70), 0.53 (0.37, 0.76), 0.30 (0.17, 0.53), 0.67 (0.52, 0.87), 0.67 (0.53, 0.86), 0.42 (0.19, 0.96), 1.39 (0.63, 2.16), 1.35 (1.13, 1.60), 3.21 (1.51, 6.81) and 1.31 (1.22, 1.41) with significant differences. Subgroup analysis showed that ginseng enhanced nausea and vomiting and QOL, ginsenosides increased ORR, DCR, QOL, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, diarrhea, CD4+/CD8+, and one- and two-year survival rates, while polysaccharides improved ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity and nausea and vomiting during chemotherapy. In conclusion, ginseng and its ingredients facilitated the therapeutic effects of chemotherapy on NSCLC patients. Ginseng had beneficial effects on alleviating ADRs and enhancing QOL, ginsenosides demonstrated beneficial effects on enhancing therapeutic effects, reducing ADRs, improving immunity, prolonging survival rates and promoting QOL, while polysaccharides showed beneficial effects on promoting therapeutic effects and reducing ADRs.

Association between Receipt of Guideline-Concordant Lung Cancer Treatment and Individual- and Area-Level Factors: A Spatio-Temporal Analysis.

BACKGROUND: Guideline-concordant treatment (GCT) of lung cancer has been observed to vary across geographic regions over the years. However, there is little evidence as to what extent this variation is explained by differences in patients' clinical characteristics versus contextual factors, including socioeconomic inequalities. METHODS: This study evaluated the independent effects of individual- and area-level risk factors on geographic and temporal variation in receipt of GCT among patients with lung cancer. Receipt of GCT was defined on the basis of the National Comprehensive Cancer Network guidelines. We used Bayesian spatial-temporal multilevel models to combine individual and areal predictors and outcomes while accounting for geographically structured and unstructured correlation and linear and nonlinear trends. RESULTS: Our study included 4,854 non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cases, reported to the Victorian Lung Cancer Registry between 2011 and 2018. Area-level data comprised socioeconomic disadvantage and remoteness data at the local government area level in Victoria, Australia. Around 60.36% of patients received GCT, and the rates varied across geographic areas over time. This variation was mainly associated with poor performance status, advanced clinical stages, NSCLC types, public hospital insurance, area-level deprivation, and comorbidities. CONCLUSIONS: This study highlights the need to address disparities in receipt of GCT among patients with lung cancer with poor performance status, NSCLC, advanced clinical stage, stage I-III SCLC, stage III NSCLC, public hospital insurance, and comorbidities, and living in socioeconomically disadvantaged areas. IMPACT: Two-year mortality outcomes significantly improved with GCT. Interventions aimed at reducing these inequalities could help to improve lung cancer outcomes.

Prognostic nutrition index affects the prognosis of patients undergoing trimodality therapy for locally advanced non-small cell lung cancer.

PURPOSE: Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. METHODS: The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. RESULTS: PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). CONCLUSIONS: Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

Sequence of biologic therapies and surgery affects survival in non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: Biologic therapy is changing the landscape of lung cancer treatment. The objectives of this study were to compare overall survival (OS) between patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant and adjuvant biologic therapy in combination with surgery and to evaluate the impact of chemotherapy on survival after combination biologic therapy and surgery. METHODS: The National Cancer Database was queried for cases of NSCLC from 2004 to 2016. Patient treatment was categorized into neoadjuvant and adjuvant biologic therapy in combination with surgery. Kaplan-Meier curves were generated to compare OS between treatment groups and between those who did and did not also undergo chemotherapy. Cox regression was used to identify factors predictive of OS. RESULTS: Six hundred seventy-three patients underwent both biologic therapy and surgery. The unadjusted overall 5-year OS was longer for patients undergoing neoadjuvant biologic therapy than for those undergoing adjuvant biologic therapy (P = .006), with OS being 56.2% and 33.0%, respectively. When comparing OS between those who did and did not undergo additional chemotherapy, no difference was observed. CONCLUSIONS: Neoadjuvant biologic therapy was associated with longer OS than adjuvant biologic therapy. Chemotherapy did not have an effect on OS when combined with biologic therapy and surgery.

Clinical features and prognostic factors in patients with bone metastases from non-small cell lung cancer.

OBJECTIVE: To investigate the clinical features and evaluate the prognostic factors in patients with bone metastases from non-small cell lung cancer (NSCLC). METHODS: We retrospectively investigated 356 patients with NSCLC with bone metastases from January 2012 to December 2017. The overall survival (OS) and 1-year survival rate were calculated by Kaplan-Meier analysis and compared by univariate analysis using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: A total of 694 sites of bone metastases were determined among the 356 patients. The most common site of bone metastases was the ribs. The median OS was 12.5 months and the 1-year survival was 50.8% in the overall population. Univariate analysis revealed that histological type, number of bone metastases, Eastern Cooperative Oncology Group performance status (ECOG PS), bisphosphonate therapy, and serum calcium, lactate dehydrogenase, and alkaline phosphatase were significantly correlated with prognosis. Multivariate analysis identified multiple bone metastases, ECOG PS ≥2, lactate dehydrogenase ≥225 U/L, and alkaline phosphatase ≥140 U/L as independent negative prognostic factors. CONCLUSION: Multiple bone metastases, high ECOG PS, and high serum alkaline phosphatase and lactate dehydrogenase are independent negative prognostic factors for bone metastases from NSCLC.

Socioeconomic disparity trends in diagnostic imaging, treatments, and survival for non-small cell lung cancer 2007-2016.

Socioeconomic status (SES) has led to treatment and survival disparities; however, limited data exist for non-small cell lung cancer (NSCLC). This study investigates the impact of SES on NSCLC diagnostic imaging, treatment, and overall survival (OS), and describes temporal disparity trends. The Ontario Cancer Registry was used to identify NSCLC patients diagnosed between 2007 and 2016. Through linkage to administrative datasets, patients' demographics, imaging, treatment, and survival were obtained. Based on median household neighborhood income, the Ontario population was divided into five income quintiles (Q1-Q5; Q1 = lowest income). Multivariable regressions assessed SES association with OS, imaging, treatment receipt, and treatment delay, and their interaction with year of diagnosis to understand temporal trends. Endpoints were adjusted for demographics, stage and comorbidities, along with treatments and imaging for OS. A total of 50 542 patients were identified. Higher SES patients (Q5 vs. Q1) showed improved 5-year OS (hazard ratio, 0.89; 95% confidence interval [CI], 0.87-0.92; P < .0001) and underwent greater magnetic resonance imaging head (stages IA-IV; odds ratio [OR], 1.24; 95% CI, 1.16-1.32; P < .0001), lung resection (IA-IIIA; OR, 1.58; 95% CI, 1.43-1.74; P < .0001), platinum-based vinorelbine adjuvant chemotherapy (IB-IIIA; OR, 1.63; 95% CI, 1.39-1.92; P < .0001), palliative radiation (IV; OR, 1.14; 95% CI, 1.05-1.25; P = .023), and intravenous chemotherapy (IV; OR, 1.45; 95% CI, 1.32-1.60; P < .0001). Lower SES patients underwent greater thoracic radiation (IA-IIIB; OR, 0.86; 95% CI, 0.79-0.94; P = .0003). Across 2007-2016, socioeconomic disparities remain largely unchanged (interaction P > .05) despite widening income inequality.

Disparities in guideline-concordant treatment for node-positive, non-small cell lung cancer following surgery.

OBJECTIVES: To examine guideline concordance across a national sample and determine the relationship between socioeconomic factors, use of recommended postoperative adjuvant therapy, and outcomes for patients with resected pN1 or pN2 non-small cell lung cancer. METHODS: All margin-negative pT1-3 N1-2 M0 non-small cell lung cancers treated with lobectomy or pneumonectomy without induction therapy in the National Cancer Database between 2006 and 2013 were included. Use of guideline-concordant adjuvant treatment, defined as chemotherapy for pN1 disease and chemotherapy with or without radiation for pN2 disease, was examined. Multivariable regression models were developed to determine associations of clinical factors with guideline adherence. Survival was estimated using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Of 13,462 patients, 10,113 had pN1 disease and 3349 had pN2 disease. Guideline-concordant adjuvant therapy was used in 6844 (67.7%) patients with pN1 disease and 2622 (78.3%) patients with pN2 disease. After multivariable adjustment, insurance status, older age, pneumonectomy, readmission, and longer postoperative stays were associated with lower likelihood of guideline concordance. Conversely, increased education level, later year of diagnosis, and greater nodal stage were associated with greater concordance. Overall, patients treated with guideline-concordant therapy had superior survival (5-year survival: 51.6 vs 36.0%; hazard ratio, 0.66; 95% confidence interval, 0.62-0.70, P < .001). CONCLUSIONS: Socioeconomic factors, including insurance status and geographic region, are associated with disparities in use of adjuvant therapy as recommended by National Comprehensive Cancer Network guidelines. These disparities significantly impact patient survival. Future work should focus on improving access to appropriate adjuvant therapies among the under insured and socioeconomically disadvantaged.

Kanglaite injection plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer: A meta-analysis of 27 RCTs.

BACKGROUND: Kanglaite injection (KLT) is a broad-spectrum anti-tumor drug, which is extracted from the seeds of the Chinese medicinal herb Coix lacryma-jobi, and has been widely used for the treatment of advanced lung cancer. PURPOSE: To evaluate the combined effects of Kanglaite injection plus platinum-based chemotherapy (PBC) on patients with stage III/IV non-small cell lung cancer (NSCLC). STUDY DESIGN: A systematic review and meta-analysis of randomized clinical trials (RCTs). MATERIALS AND METHODS: Twelve databases were searched from their inceptions until July 05, 2019. All the RCTs comparing the efficacy and safety of Kanglaite injection plus PBC versus PBC alone were selected. Analyses were performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis (TSA). Disease control rate (DCR) was defined as the primary endpoint, objective response rate (ORR), survival rate, quality of life (QOL), cellular immunity function, and toxicities were defined as the secondary endpoints. RESULTS: Twenty-seven RCTs recruiting 2,243 patients with stage III/IV NSCLC were included. The results showed that, compared with PBC alone, Kanglaite injection plus PBC improved DCR (RR = 1.20, 95% CI 1.15-1.26, p < 0.00001), ORR (RR = 1.45, 95% CI 1.31-1.60, p < 0.00001), 1-year survival rate (RR = 1.20, 95% CI 1.02-1.43, p = 0.03), QOL (RR = 1.32, 95% CI 1.25-1.40, p < 0.00001), CD4+T cells (WMD = 4.86, 95% CI 4.00-5.73, p < 0.00001), CD4+/CD8+ ratio (WMD = 0.19, 95% CI 0.07-0.31, p < 0.002), and reduced severe toxicities by 59% (RR = 0.41, 95% CI 0.33-0.51, p < 0.00001). Most results were robust and the quality of evidence was from moderate to low. CONCLUSIONS: Kanglaite injection in combination with PBC showed significantly higher efficacy than PBC alone in the treatment of stage III/IV NSCLC. Moreover, the combination therapy can improve cellular immunity and attenuate the severe toxicities caused by chemotherapy. However, high-quality RCTs are warranted to further assess the effects of the combined therapy.

Genetic Polymorphisms in the Vitamin D Pathway and Non-small Cell Lung Cancer Survival.

Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lung cancer risk. The aim of this study is to assess if genetic polymorphisms in the VD pathway are associated with the prognosis of non-small cell lung cancer (NSCLC). Nine single nucleotide polymorphisms (SNPs) in five genes in the VD pathway were genotyped with the TaqMan assays in 542 patients with primary NSCLC, and the relationships between these SNPs and overall survival were evaluated. We found that SNP rs10741657 in the CYP2R1 gene was associated with the prognosis of NSCLC, especially in elderly patients and not being treated with chemotherapy. Some of the VD pathway-related genetic polymorphisms may influence the prognosis of NSCLC. More research is needed to further confirm the finding and test if VD supplements can be used for NSCLC treatment.

A prospective observational study of on-treatment plasma homocysteine levels as a biomarker of toxicity, depression and vitamin supplementation lead-in time pre pemetrexed, in patients with non-small cell lung cancer and malignant mesothelioma.

OBJECTIVES: Vitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine reflects deficiency in vitamin B12 and folate, and is suppressed by supplementation. This observational study of 112 patients receiving pemetrexed-based chemotherapy assessed homocysteine levels after 3 weeks of vitamin supplementation, hypothesising high levels would correlate with ongoing deficiency, thus increased toxicity. MATERIAL AND METHODS: Primary endpoint was the composite of proportion of patients with treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, comparing those with normal plasma homocysteine (successfully supplemented, SS) and those with high homocysteine (unsuccessfully supplemented, USS). Secondary endpoints included toxicity and analyses for depression. Post-hoc analysis examined correlation between interval of vitamin and folate supplementation and pemetrexed on primary endpoint and grade 3-4 toxicities. RESULTS: Eighty-four patients (84%) were successfully supplemented (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in SS group was 44.0% (95% confidence interval [CI] 33.2%-55.3%) and in USS group was 18.8% (95% CI 4.0%-45.6%) (p = 0.09). Twelve percent of patients gave a past history of depression however 66% of patients had an on study Hospital Anxiety and Depression (HAD) score of >7. Supplementation status was not associated with depression. The median overall survival (OS) was 11.8 months (95% CI 8.6-16.5) in the SS group and 8.8 months (95% CI 6.6-16.2) in the US group (p = 0.5). The number of days (<7 or ≥ 7 days) between vitamin B12 and folate initiation and pemetrexed administration, had no effect on the primary endpoint and grade 3-4 toxicities. CONCLUSION: On-treatment homocysteine levels were not a biomarker of toxicity or depression. Standard vitamin supplementation is adequate in the majority of patients receiving pemetrexed. High HAD score were noted in this population giving an opportunity for mental health intervention. The lead-in time for vitamin supplementation can be short.

La inmunoterapia una alternativa terapéutica en ancianos con cáncer de pulmón de células no pequeñas / Immunotherapy, a therapeutic option in elder people with non small cells lung cancer

RESUMEN El cáncer es un problema prioritario de salud pública en el mundo. En Cuba constituye la segunda causa de muerte en la mayoría de grupos de edades y fundamentalmente en la población mayor de 60 años. El objetivo fue evaluar el impacto de la inmunoterapia como una alternativa terapéutica que mejora las funciones de supervivencia en pacientes ancianos con cáncer de pulmón de células no pequeñas. Se realizó un estudio analítico experimental donde el universo estuvo integrado por 123 ancianos con diagnóstico de cáncer de pulmón los cuales fueron tratados con inmunoterapia en Matanzas. Fueron utilizadas variables de control a las cuales se les aplicaron las medidas de resumen correspondientes utilizando las pruebas de hipótesis de chi cuadrado y las razones de verosimilitud para su análisis y estadístico y fueron evaluadas las funciones de supervivencia usando las curvas de Kaplan Meier. Se demostró la eficacia y seguridad de la inmunoterapia en el tratamiento de los pacientes estudiados. Por ello consideramos que el impacto secuencial de la combinación de la cirugía, la quimioterapia, la radioterapia y las terapias biológicas, tiende a prolongar la supervivencia de los pacientes que sufren cáncer de pulmón de células no pequeñas con una calidad de vida éticamente aceptable. Las nuevas terapias inmunológicas que consisten en devolver al sistema inmunológico de los pacientes, la capacidad de reconocer al tumor como extraño, y por tanto luchar contra él; han producido respuestas y beneficios muy importantes (AU).

SUMMARY Cancer is a priority public health problem in the world. In Cuba, it is the second cause of death in most age groups and mainly in the population aged over 60 years. To evaluate the impact of immunotherapy as a therapeutic alternative that improves survival functions in elder patients with non-small cell lung cancer. An experimental analytical study was carried out; the universe was composed by 123 elder people diagnosed with lung cancer who were treated with immunotherapy in Matanzas. Control variables were used to which the corresponding summary measures were applied using chi-square hypothesis tests and likelihood ratios for their analysis and statistics; survival functions were evaluated using Kaplan Meier curves. The efficacy and safety of immunotherapy in the treatment of the studied patients was demonstrated. Therefore, the authors believe that the sequential impact of the combination of surgery, chemotherapy, radiotherapy and biological therapies tends to extend the survival of patients suffering from non-small cell lung cancer with an ethically acceptable life quality. The new immunological therapy, consisting in returning to the patients´ immunologic system the capacity of recognizing a tumor as foreign, and therefore, fighting against it, have yielded very important answers and benefits (AU).