Advanced Nonsmall-cell Cancer Research Articles

Efficacy and safety of PD-1/PD-L1 inhibitors in elderly patients with advanced non-small cell lung cancer.

This study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC ≥70 years old who received PD-1/PD-L1 inhibitors in our hospital were retrospectively analyzed. According to age, the patient were stratified as follows: 70-75 years old, 76-80 years old, and >80 years old. Kaplan-Meier method was used for survival analysis, and univariate and multivariate Cox proportional hazards regression models were used to analyze the correlation between different clinical characteristics and survival. A total of 58 elderly patients with advanced non-small cell cancer were enrolled in this study. Patients aged 70-75, 76-80, and >80 years old were 32, 19, and 7, respectively. For the all, median OS was 17.0months, and PFS was 7.0months. PFS and OS did not differ according to age (P = 0.396, 0.054, respectively). Univariate analysis showed that PS of 0-1, stage III, first-line therapy and irAEs were associated with longer PFS, and PS of 0-1, stage III, and first-line therapy were associated with longer OS. Multivariate analysis showed that patients with stage III had longer PFS. PFS and OS of patients with PS ≥ 2 were significantly shorter than those of patients with PS of 0-1. In the present real-world retrospective cohort, PD-1/PD-L1 inhibitors are effective and well tolerated in elderly patients with advanced NSCLC. Immunotherapy should be actively used as early as possible in older patients advanced NSCLC.

The cost-effectiveness of cemiplimab plus chemotherapy as the first-line treatment for advanced non-small cell lung cancer.

Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system. Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs' costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes. Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100mg), and the HR of PFS, all significantly impacted the model's results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT. Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC.

Patlak-Ki derived from ultra-high sensitivity dynamic total body [18F]FDG PET/CT correlates with the response to induction immuno-chemotherapy in locally advanced non-small cell lung cancer patients.

This study aimed to investigate the predictive value of metabolic features in response to induction immuno-chemotherapy in patients with locally advanced non-small cell cancer (LA-NSCLC), using ultra-high sensitivity dynamic total body [18F]FDG PET/CT. The study analyzed LA-NSCLC patients who received two cycles of induction immuno-chemotherapy and underwent a 60-min dynamic total body [18F]FDG PET/CT scan before treatment. The primary tumors (PTs) were manually delineated, and their metabolic features, including the Patlak-Ki, Patlak-Intercept, maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were evaluated. The overall response rate (ORR) to induction immuno-chemotherapy was evaluated according to RECIST 1.1 criteria. The Patlak-Ki of PTs was calculated from the 20-60min frames using the Patlak graphical analysis. The best feature was selected using Laplacian feature importance scores, and an unsupervised K-Means method was applied to cluster patients. ROC curve was used to examine the effect of selected metabolic feature in predicting tumor response to treatment. The targeted next generation sequencing on 1021 genes was conducted. The expressions of CD68, CD86, CD163, CD206, CD33, CD34, Ki67 and VEGFA were assayed through immunohistochemistry. The independent samples t test and the Mann-Whitney U test were applied in the intergroup comparison. Statistical significance was considered at P < 0.05. Thirty-seven LA-NSCLC patients were analyzed between September 2020 and November 2021. All patients received two cycles of induction chemotherapy combined with Nivolumab/ Camrelizumab. The Laplacian scores showed that the Patlak-Ki of PTs had the highest importance for patient clustering, and the unsupervised K-Means derived decision boundary of Patlak-Ki was 2.779ml/min/100g. Patients were categorized into two groups based on their Patlak-Ki values: high FDG Patlak-Ki (H-FDG-Ki, Patlak-Ki > 2.779ml/min/100g) group (n = 23) and low FDG Patlak-Ki (L-FDG-Ki, Patlak-Ki ≤ 2.779ml/min/100g) group (n = 14). The ORR to induction immuno-chemotherapy was 67.6% (25/37) in the whole cohort, with 87% (20/23) in H-FDG-Ki group and 35.7% (5/14) in L-FDG-Ki group (P = 0.001). The sensitivity and specificity of Patlak-Ki in predicting the treatment response were 80% and 75%, respectively [AUC = 0.775 (95%CI 0.605-0.945)]. The expression of CD3+/CD8+ T cells and CD86+/CD163+/CD206+ macrophages were higher in the H-FDG-Ki group, while Ki67, CD33+ myeloid cells, CD34+ micro-vessel density (MVD) and tumor mutation burden (TMB) were comparable between the two groups. The total body [18F]FDG PET/CT scanner performed a dynamic acquisition of the entire body and clustered LA-NSCLC patients into H-FDG-Ki and L-FDG-Ki groups based on the Patlak-Ki. Patients with H-FDG-Ki demonstrated better response to induction immuno-chemotherapy and higher levels of immune cell infiltration in the PTs compared to those with L-FDG-Ki. Further studies with a larger patient cohort are required to validate these findings.

BITH, a blood-based metric of intratumor heterogeneity, is associated with clinical response to immune checkpoint blockade in non-small cell lung cancer

Intratumor heterogeneity (ITH) has been associated with poor prognosis in advanced non-small cell cancer (NSCLC) patients receiving immune checkpoint blockade (ICB) therapies. However, there is currently no evidence supporting an ITH metric as a predictor of clinical benefit from ICB. The unique advantages of blood make it a promising material for ITH estimation and relevant applications. This study aims to develop and validate a blood-based ITH index for predicting ICB response. NSCLC patients from the OAK and POPLAR clinical trials were used as the training cohorts for algorithm development. Survival analyses with overall survival (OS) and progression-free survival (PFS) as endpoints were performed to assess clinical response. The predictive value of bITH was subsequently validated with an independent cohort of 42 NSCLC patients treated with PD-1 blockade. bITH was significantly associated with the differential OS and PFS elicited by atezolizumab vs. docetaxel in both univariable and multivariable analyses in the OAK patients, suggesting bITH as an independent predictor for response to ICB. Moreover, compared with blood tumor mutation burden (bTMB), bITH enabled greater OS segregation and comparable PFS segregation, and obtained a predictive role regardless of bTMB status. Moreover, the association between bITH and PFS was validated with an independent cohort. Patients with low blood-based ITH metric manifest significant OS and PFS benefit from immunotherapy versus chemotherapy. Future research is awaited to corroborate our findings and to enrich the clinical utility of ITH. This study was supported by the National Natural Science Foundation of China (Nos. 81972718 and 81572321), the Natural Scientific Foundation of Zhejiang Province, China (No. LY19H160007), the Science and Technology Program for Health and Medicine in Zhejiang Province, China (No. 2021KY541), the Scientific Research Project, Science and Technology Department of Sichuan Province (No. 21YYJC1616), the Scientific Research Project, Sichuan Medical Association (No. S20002), Wu Jieping Medical Foundation (No. 320.6750), and 2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (No. 2022-L023).

中晚期非小细胞癌类型患者新辅助治疗的研究现状

中晚期非小细胞癌类型患者新辅助治疗的研究现状

EP05.02-019 Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Surgical Outcomes in a Regionalized Pulmonary Oncology Network

Neoadjuvant therapy (NAT) allows pre-operative tumor downstaging and evaluation of pathological response. Clinical trials have demonstrated benefit of using NAT in the context of locally advanced non-small cell cancer (NSCLC). However, NAT is not commonly employed around the world and data are lacking as to how to establish a NAT program for locally advanced resectable NSCLC. The aim of this study is to evaluate the evolution in care patterns for patients with resectable locally advanced NSCLC within a regionalized pulmonary oncology academic network and to assess the impact of transition towards a large-scale NAT program.

Apport de l’immunothérapie dans les stades non métastatiques et non résécables: Contribution of immunotherapy in non-metastatic and unresectable stages

Since many years, the standard treatment of locally advanced non-small cell cancer is based on a association of chemotherapy and radiotherapy. A concurrent plan is to be favored to a sequential plan. Since 2017, following results of PACIFIC study, consolidation immunotherapy with durvalumab (anti-PD-L1 monoclonal antibody) after concurrent chemo-radiotherapy became a standard of care in patients with a PD-L1 expressing tumor. Others studies confirm this strategy. Recently, a real-life study, PACIFIC-R, shows same results than PACIFIC trial in terms of progression-free survival and safety. The next step is to integrate chekpoints inhibitors during concurrent chemo-radiotherapy or before chemo-radiotherapy as induction treatment. Many phase I/II trials show that this approach is faisabile in terms of toxicity, particularly in terms of pulmonary toxicity. Nevertheless, these studies are not able to show a survival benefit. We wait results of currently phase III studies in this setting.© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

A Randomized Phase Ii Trial of Standard Versus Low-Dose Nab-Paclitaxel for Previously Treated Advanced Non-Small Cell Cancer: JMTO LC14-01

A Randomized Phase Ii Trial of Standard Versus Low-Dose Nab-Paclitaxel for Previously Treated Advanced Non-Small Cell Cancer: JMTO LC14-01

Clinical cases of pembrolisumab immunotherapy treatment in patients with non-small lung cancer with high level of PD-L1 expression in fist line therapy

In Russian Federation, lung cancer is the most frequently diagnosed malignant tumor among men and the fourth in the structure of morbidity among women, also occupying a leading position in the structure of mortality [1]. Non-small cell cancer (NSCLC) accounts for about 80 % of all lung tumors. In turn, in the structure of NSCLC, the most common types are adenocarcinoma (50 %) and squamous cell lung cancer (30 %). The appearance of drugs based on blocking immune checkpoints, in particular PD-1 and PD-L1, has changed the approach to the treatment of NSCLC. Currently, the determination of the optimal tactics for treatment tumors without activated mutations is based on predicting the sensitivity of the tumor to immunotherapy. Evaluation of PD-L1 expression makes it possible to divide patients with NSCLC into several groups of the level of sensitivity to modern immune checkpoint inhibitors. Thus, three groups are distinguished: with negative (≤ 1 %), intermediate (1–49 %) and high (≥ 50 %) expression of PD-L1. The latter includes 23–28 % of patients with advanced NSCLC, regardless of the histological form of the tumor [3]. There are also reasons to believe that in the near future a subgroup of patients with ultra-high expression (&gt; 75 %) PD-L1 will be identifid, in which it is expected to achieve the maximum advantage from treatment with monoimmunotherapy. Pembrolizumab was approved for the treatment of advanced NSCLC with high level of PD-L1 expression (≥ 50 %) with the absence of EGFR / ALK mutations in the fist line of therapy following the publication of the results of the randomized phase III clinical trial KEYNOTE-024. In this study, the median overall survival in the pembrolizumab monotherapy arm was 30.0 months compared with 14.2 months with standard platinum-containing therapy [5]. These data formed the basis for the registration of the fist cytostatic-free regimen in patients with NSCLC without activating mutations. The subsequent study KEYNOTE-042 was an attempt to assess the effect of pembrolizumab in a wider group of patients – with a positive level of PD-L1 expression (PD-L1 ≥ 1 %; ≥ 20 %; ≥ 50 %). In general, the results of the study were positive, but many authors drew attention to the fact that the greatest effect of monoimmunotherapy with pembrolizumab is obtained by patients with a high level of PD-L1 expression. Median overall survival in this study was 20.0 months in the pembrolizumab group and 12.2 months in the chemotherapy group for all patients regardless of PD-L1 status. In this article two clinical cases of the use of the PD-L1 inhibitor pembrolizumab in patients with non-small cell lung cancer and high levels of PD-L1 expression are presented.

Effectiveness of EGFR-TKI rechallenge immediately after PD-1 blockade failure.

BackgroundThere is currently insufficient information available on effective therapies that can be administered to patients with non‐small cell cancer (NSCLC) who develop resistance to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). However, sequential treatment via programmed death‐1 (PD‐1) blockade followed by EGFR‐TKI rechallenge is suggested to improve the therapeutic efficacy in such patients.MethodsA total of 75 patients with advanced NSCLC harboring sensitive EGFR mutations treated with afatinib, erlotinib, or gefitinib after EGFR‐TKI treatment failure were retrospectively analyzed. Among them, 13 patients were treated with EGFR‐TKI rechallenge immediately after the failure of PD‐1 blockade therapy (experimental group) and the remaining 62 patients did not receive PD‐1 inhibitor therapy before EGFR‐TKI rechallenge (control group). Blood samples were collected at two time points; before the initiation of anti‐PD‐1 therapy and at EGFR‐TKI rechallenge.ResultsThe objective response rates of EGFR‐TKI rechallenge in the experimental and control groups were 46.1% and 16.1%, respectively, with a significant difference (p = 0.026). In the experimental group, the median progression‐free survival (PFS) and overall survival (OS) after EGFR‐TKI rechallenge were 5.0 and 25.0 months, respectively, and no statistically significant difference in the percentage of lymphocytes before immune checkpoint inhibitor (ICI) therapy and EGFR‐TKIs was observed in patients with partial response (PR) and without PR after EGFR‐TKI rechallenge. In particular, the sequential treatment of PD‐1 blockade therapy followed by EGFR‐TKI rechallenge was consecutively repeated three times in two out of 13 patients in the experimental group, and EGFR‐TKI rechallenge consecutively for the third time yielded a PR without increased toxicities.ConclusionsEGFR‐TKI rechallenge immediately after PD‐1 blockade treatment was identified as an effective therapy for NSCLC patients with resistance to EGFR‐TKIs.

Rural vs urban inequalities in stage at diagnosis for lung cancer

ObjectivesEarly diagnosis of lung cancer increases the chance of survival. The aim of this study was to measure the relationship between geographic residence in Saskatchewan and stage of lung cancer at the time of diagnosis. Materials and methodsRetrospective cohort analysis of 2,972 patients with a primary diagnosis of either non-small cell cancer (NSCLC) or small cell lung cancer (SCLC) between 2007 and 2012 was performed. Incidence proportion of early and advanced stage cancer, and relative risk of being diagnosed with advanced-stage lung cancer relative to early-stage was calculated. ResultsCompared to urban Saskatchewan, rural Saskatchewan lung cancer patients had a higher relative risk of advanced stage NSCLC (relative risk [RR] = 1.11, 95% confidence interval [CI]: 1.01–1.22). Rural Saskatchewan was further subdivided into north and south. The relative risk of advanced stage NSCLC in rural north Saskatchewan compared to urban Saskatchewan was even greater (RR = 1.17, 95% CI: 1.03–1.31). Although not statistically significant, there was a trend for a higher incidence of advanced stage SCLC in rural and rural north vs urban Saskatchewan (RR = 1.16, 95% CI: 0.95–1.43 and RR = 1.22; 95% CI: 0.94–1.58, respectively). There was a higher incidence proportion of advanced stage NSCLC in rural areas relative to urban (31.6–34.4 vs 29.5 per 10,000 people). ConclusionPatients living in rural Saskatchewan have higher incidence proportion of and were more likely to present with advanced stage NSCLC in comparison to urban Saskatchewan patients at time of diagnosis. This inequality was even greater in rural north Saskatchewan.

Can Ipilimumab restore immune response in advanced NSCLC after progression on anti‐PD‐1/PD‐L1 agents?

Anti‐PD‐1/PD‐L1 agents play a crucial part in the treatment of non‐small cell cancer (NSCLC) demonstrating improved overall response rate (ORR) and overall survival (OS). Recent studies evaluating combination treatment with anti‐PD‐1 and anti‐CTLA‐4 suggests improved outcome but also increased toxicity. Evidence is scarce regarding subsequent treatment with immune checkpoint inhibitors (ICPI) after progression on anti‐PD‐1/PD‐L1. A total of 15 patients were treated with a combination of anti‐PD1 agent and ipilimumab after confirmed progression of disease on anti‐PD1/PDL1 alone during 2017. Clinical data were retrieved retrospectively. Disease control rate (DCR) was defined as partial response (PR) or stable disease (SD). The overall DCR was 33.3% (n = 5); two patients with PR and three patients with SD, three of whom had prior documented disease control on anti‐PD1. The immune‐related adverse event (irAE) rate was 40% (n = 6); two patients had grade 3 AE and one patient died of pneumonitis. While the median time to progression was two months (range 0.5–16), four of the five patients with PR/SD experienced durable benefit for 8–16 months. This small retrospective cohort of heavily pretreated unselected patients suggests ipilimumab might reboost the immune response in patients with advanced NSCLC following progression of disease on anti‐PD1 therapy, while delaying exposure to the higher toxicity rates associated with upfront combination therapy. This strategy should be explored prospectively.

Efficacy and safety of first-line carboplatin-versus cisplatin-based chemotherapy for non-small cell lung cancer: A meta-analysis

ObjectivesPlatinum-based chemotherapy is the mainstay of first-line (1L) therapy for advanced non-small cell cancer (NSCLC). The objective of this study was to evaluate the relative efficacy, safety, and health-related quality of life (HRQoL) of carboplatin- versus cisplatin-based chemotherapy in 1L NSCLC. Materials and MethodsA meta-analysis by the Cochrane group (2013) was updated. Systematic searches of CENTRAL, Medline, Embase, Latin American and Caribbean Health Sciences database, clinicaltrials.gov and conference proceedings were conducted to include randomized controlled trials (RCTs) published between 2013-January 2018 which compared carboplatin and cisplatin combined with: gemcitabine, vinorelbine, docetaxel, paclitaxel, irinotecan, or pemetrexed. Endpoints included overall survival (OS), one-year OS, objective response rate (ORR), grade 3/4 drug-related toxicities, and HRQoL. ResultsTwelve RCTs (2,048 patients) were identified from 4,139 records for inclusion in the meta-analysis. There were no significant differences in OS (hazards ratio [HR]: 1.08, 95% confidence interval [CI]: 0.96, 1.21) and one-year OS (relative risk [RR]: 0.97, CI: 0.89, 1.07) between carboplatin- and cisplatin-based chemotherapy. A small effect on ORR favouring cisplatin was detected (RR = 0.88; CI: 0.78, 0.99). Differences in drug-related toxicities were observed between carboplatin- and cisplatin-based chemotherapy for thrombocytopenia, anaemia, neurotoxicity, and the risk of nausea/vomiting. Three RCTs comparing HRQoL between carboplatin- and cisplatin-based chemotherapy found no significant differences. ConclusionsThis updated evidence base corroborates findings of previous meta-analyses showing no difference in OS between carboplatin- and cisplatin-based chemotherapy, despite a slight benefit in ORR for cisplatin. Toxicity profiles should be considered alongside patients’ comorbidities in the choice of therapy.

Discovery of 7-bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as the potential epidermal growth factor receptors for tyrosine kinase inhibitors

Small molecule tyrosine kinase inhibitors (TKIs) targeting at epidermal growth factor receptor (EGFR) in recent years have made great progress in the treatment of advanced non-small cell cancer (NSCLC). Although as the first-line treatment for sensitizing EGFR mutation-positive metastatic NSCLC, gefitinib has also behaved quite a lot of side effect and EGFR tolerance. Herein, a novel series of 7-bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives were designed and synthesized, and screened for their inhibitory activity on the EGFR high-expressing human lung adenocarcinoma cell line A549 and human large cell lung cancer cell line NCI-H460 by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetric assay. The calculated IC50 values were reported. Compound 8h demonstrated the most potent inhibitory activity (IC50 = 9.57 ± 2.20 μmol L–1 for A549 and IC50 = 13.04 ± 1.21 μmol L–1 for NCI-H460), comparable to the positive-control gefitinib (IC50 = 8.58 ± 1.65 μmol L–1 for A549 and IC50 = 18.66 ± 5.01 μmol L–1 for NCI-H460). Conclusively, 7-bromo- 1,4-dihydrothieno[3’,2’:5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as the EGFR–TKIs were discovered, and could be used as potential leading compounds for further research.

Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib.

Nintedanib is an oral, small-molecule tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis and patients with advanced non-small cell cancer of adenocarcinoma tumour histology. Nintedanib competitively binds to the kinase domains of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). Studies in healthy volunteers and in patients with advanced cancer have shown that nintedanib has time-independent pharmacokinetic characteristics. Maximum plasma concentrations of nintedanib are reached approximately 2–4 h after oral administration and thereafter decline at least bi-exponentially. Over the investigated dose range of 50–450 mg once daily and 150–300 mg twice daily, nintedanib exposure increases are dose proportional. Nintedanib is metabolised via hydrolytic ester cleavage, resulting in the formation of the free acid moiety that is subsequently glucuronidated and excreted in the faeces. Less than 1% of drug-related radioactivity is eliminated in urine. The terminal elimination half-life of nintedanib is about 10–15 h. Accumulation after repeated twice-daily dosing is negligible. Sex and renal function have no influence on nintedanib pharmacokinetics, while effects of ethnicity, low body weight, older age and smoking are within the inter-patient variability range of nintedanib exposure and no dose adjustments are required. Administration of nintedanib in patients with moderate or severe hepatic impairment is not recommended, and patients with mild hepatic impairment should be monitored closely and the dose adjusted accordingly. Nintedanib has a low potential for drug–drug interactions, especially with drugs metabolised by cytochrome P450 enzymes. Concomitant treatment with potent inhibitors or inducers of the P-glycoprotein transporter can affect the pharmacokinetics of nintedanib. At an investigated dose of 200 mg twice daily, nintedanib does not have proarrhythmic potential.

MS30.05 Nutritional Management During Radical Radiotherapy

Curative intent fractionated external beam radiotherapy (RT) with or without chemotherapy is used to treat locally advanced non-small cell cancer (NSCLC) and common side effects include anorexia, oesophagitis and fatigue, all of which can all impact on nutritional status. Previous research has shown that up to one third of lung cancer patients treated with RT experience clinically significant weight loss1 while one third of lung cancer patients present with malnutrition prior to even commencing RT 2. The negative impact of weight loss and malnutrition on patient and clinical outcomes is well established across all modes of cancer treatment including chemoradiotherpy3. There is limited evidence available relating to effective nutritional support strategies to prevent or treat weight loss and malnutrition in lung cancer4. There may be a role for enteral feeding where severe oesophagitis occurs in order to support patients through radical radiotherapy and its recovery1. The nutrition intervention demonstrated to be most effective in other tumours undergoing radiotherapy treatment is intensive individualised dietary counselling5 and the presence of dedicated dietetic services to head and neck and oesophageal cancer patients is well established in the U.K with dietitians identified as core members of the multi-disciplinary team. This session will explore the impact of a worsening nutritional status on clinical and patient outcomes and discuss the nutritional interventions that may be of benefit. It will also consider the role of a dedicated lung cancer dietitian and the impact this can have on patients with lung cancer. 1. Kiss, N., Isenring, E., Gough, K. et al (2014) The prevalence of weight loss during (chemo)radiotherapy treatment for lung cancer associated patient- and treatment-related factors. Clin Nutr, 33: 1074-1080 2. Unsal, D., Bulent, M., Akmansu, M. et al (2006) Evaluation of nutritional status in cancer patients receiving radiotherapy. Am J Clin Oncol 29: 183-188 3. Sanders, K., Hendricks, L., Troost. et al. (2016) Early weight loss during chemoradiotherapy has a detrimental impact on outcome in NSCLC. J Thor Oncol, 11: 873-879 4. Kiss, N., Krishnasamy, M. and Iserning, E. (2013) The effects of nutrition intervention in lung cancer patients undergoing chemotherapy and/or radiotherapy: a systematic review. Nutr Cancer, 66: 47-56 5. Lee, J., Leong L. and Lim, S. (2016) Nutrition intervention approaches to reduce malnutrition in oncology patients: a systematic review. Support Care Cancer, 24: 469-480. radical radiotherapy, NSCLC, nutrition

A retrospective analysis of the efficacy of immune checkpoint inhibitors (ICIs) to advanced non-small cell cancer (NSCLC) patients (pts) with central nerve system (CNS) metastasis.

e21042Background: In clinical practice of advanced NSCLC pts, a control of CNS metastasis is important issue. Several clinical trials of ICIs have demonstrated the survival benefit in advanced NSCL...

Acquired resistance mechanisms of EGFR-TKI in advanced non-small cell lung cancer

Since the development of molecular biology, the treatment of advanced non-small cell cancer is shifting from traditional chemotherapy into molecular targeted therapy with genotyping as a guide′s help. The most widely used is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). With the application of EGFR-TKIs, the resistances to EGFR inhibitors are paid more and more attention, in recent years. The main mechanisms of acquired resistances are as follows: secondary mutation of the EGFR gene, amplification of c-MET, Her2 and other target genes, histological transformation, activation of the bypass mechanisms, loss of p53, the relief of negative feedback loops, overlap of mechanisms, etc. Key words: Carcinoma, non-small-cell lung; Drug resistance, neoplasm; Molecular targeted therapy

Social factors, treatment, and survival in patients with advanced-stage non-small cell lung cancer

Background: Lung cancer is the leading cause of cancer death in North America with at least 40% of patients presenting with advanced, incurable non-small cell cancer (NSCLC) at the time of diagnosis. Chemotherapy has been shown to increase median survival in patients with a good performance status [Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2]. Objective: To determine factors associated with treatment in patients presenting with advanced NSCLC in two academic community-based hospital settings. Methods: Data were extracted from the 2009-2010 Scripps Cancer Registry. Advanced NSCLC patients were followed from initial diagnosis until death. The influence of socioeconomic status, performance status and access to care on the decision to pursue treatment and the correlating overall survival was assessed. Results: Chemotherapy was given to 64% of 111 patients from Scripps Mercy Hospital (SMH) and Scripps Green Hospital (SGH) diagnosed with advanced NSCLC. Chemotherapy was given to 58.8% of SMH patients and 78.3% of SGH patients (P=0.03). Patients with an ECOG status between 0-2 were more likely to receive chemotherapy compared with patients whose ECOG status was 3-4 (81% versus 0%, respectively, P<0.001). Those tested for the epidermal growth factor (EGFR) mutation were more likely to receive chemotherapy, compared to those not tested (96% versus 60%, P<0.001). Conclusions: Chemotherapy utilization for advanced NSCLC is increasing over time. Chemotherapy administration is associated with socioeconomic status, performance status, and access to care, relationships that likely reflect evolving clinical practice patterns.

XRCC3 Thr241Met Is Associated with Response to Platinum-Based Chemotherapy but Not Survival in Advanced Non-Small Cell Lung Cancer

BackgroundA lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC), while the conclusion is still conflicting.Materials and MethodsWe conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to estimate the association strength.ResultsA total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116–1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087–2.004, Pheterogeneity = 0.696). This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929–1.261, Pheterogeneity = 0.564), and there was no difference between Asian and Caucasian population.ConclusionsThese findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.