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Anguilliformes, also known as “true eels”, are an ecologically diverse group of predominantly marine origin whose members were easily recognized by their extremely elongated bodies with reduced cross-sectional areas and universal lack of pelvic fins. The Marine Eels were collected from landing centres of Parangipettai coastal waters and identified based on their morphometric and meristic characters. The newly recorded species were used for the barcoding analysis. Information on molecular taxonomy of marine eels was very meagre and hence, the present study was aimed to study the barcoding of marine eels which were present along the southeast coast of India. The cube of lateral muscle was exercised for DNA isolation followed by its amplification. Cluster IX 2.06 was used to align the nucleotide sequences (Thomson, 1997). The evolutionary history was inferred using the Neighbor-Joining method (Saitou and Nei, 1987). The evolutionary distances were computed using the Maximum Composite Likelihood method (Tamura et al., 2004). The barcodes sequences were submitted in NCBI (National centre for Biotechnological Information). The species within genera of Muraenidae, Muraenesocidae and Ophichthidae family were clustered in a same clade with high bootstrap value. The evolutionary relationships of six species were analyzed using neighbor joining method. This results of phylogenetic tree showed maximum genetic relatedness with the sequenced results which were submitted in gene bank.

The oncogenic role ERBB2 amplification is well established in breast and gastric cancers. This has led to the development of a well‐known portfolio of monoclonal antibodies and kinase inhibitors targeting the ERBB2 kinase. More recently, activating mutations in the ERBB2 gene have been increasingly reported in multiple solid cancers and were shown to play an oncogenic role similar to that of ERBB2 amplification. Thus, ERBB2 mutations define a distinct molecular subtype of solid tumors and serve as actionable targets. However, efforts to target ERBB2 mutation has met with limited clinical success, possibly because of their low frequency, inadequate understanding of the biological activity of these mutations, and difficulty in separating the drivers from the passenger mutations. Given the current impetus to deliver molecularly targeted treatments for cancer, there is an important need to understand the therapeutic potential of ERBB2 mutations. Here we review the distribution of ERBB2 mutations in different tumor types, their potential as a novel biomarker that defines new subsets in many cancers, and current data on preclinical and clinical efforts to target these mutations. IMPLICATIONS FOR PRACTICE. A current trend in oncology is to identify novel genomic drivers of solid tumors and developing precision treatments that target them. ERBB2 amplification is an established therapeutic target in breast and gastric cancers, but efforts to translate this finding to other solid tumors with ERBB2 amplification have not been effective. Recently the focus has turned to targeting activating ERBB2 mutations. The year 2018 marked an important milestone in establishing ERBB2 mutation as an important actionable target in multiple cancer types. There have been several recent preclinical and clinical studies evaluating ERBB2 mutation as a therapeutic target with varying success. With increasing access to next‐generation sequencing technologies in the clinic, oncologists are frequently identifying activating ERBB2 mutations in patients with cancer. There is a significant need both from the clinician and bench scientist perspectives to understand the current state of affairs for ERBB2 mutations.

Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450* specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors. Merit Review Award, Medical Research Service, Department of Veterans AffairsUS Department of Veterans Affairs [I01 BX000545]; Veterans AffairsUS Department of Veterans Affairs [I01BX000545] Funding Source: NIH RePORTER Part of A. H.'s time was supported by a Merit Review Award (I01 BX000545), Medical Research Service, Department of Veterans Affairs.

e21009 Background: Primary pulmonary salivary gland-type carcinomas (PSGC) are rare tumors. There are limited data on the role of adjuvant chemotherapy after surgical resection of these tumors. Here, we examine the role of adjuvant chemotherapy in the management of resected PSGC. Methods: The National Cancer Database was queried to identify patients with PSGC who underwent surgical resection. Histology codes 8200- adenoid cystic carcinoma (ACC), 8430- mucoepidermoid carcinoma (MEC), 8550- acinic cell carcinoma (AIC) and 8551- adenocarcinoma, acinar predominant were used. Patients were divided based on chemotherapy status. Summary and univariate analysis was performed. Multivariable proportional hazard regression analyses were used to obtain hazard ratios (HR). Results: A total of 6685 patients, with a mean (±SD) age of 66.1 ± 11.0 years, were included; 4148 (62%) were females. Most patients were Caucasian (84%). Chemotherapy was administered in 1141 patients (17%); multiagent chemotherapy: n = 1034 (91%). AIC was the most common subtype (n = 6302, 94%) followed by MEC (n = 304, 4.6%) and ACC (n = 73, 1.1%). Patients who received chemotherapy were younger (64.0 ± 9.0 vs 66.5 ± 11.3; p < 0.001), otherwise, there was no significant difference in baseline demographics. Unadjusted 5-year survival for stage I PSGC was significantly lower in the chemotherapy arm (60.5% vs 72%, p < 0.001). Chemotherapy did not improve survival in resected stage II or III PSGC. Overall survival was inferior with chemotherapy on multivariable analysis (adjusted HR: 1.32, 95%CI (1.13-1.55), p = 0.0006). Older age, male gender, positive margins, higher clinical stage, comorbidities, rural population and pneumonectomy were associated with lower overall survival (Table). Conclusions: Contrary to previous studies AIC is the most common tumor type among PSGC. Adjuvant chemotherapy is associated with worse survival in resected PSGC and current guidelines for administering adjuvant chemotherapy in resected lung cancer is inadequate for this population. [Table: see text]

e21637 Background: In the Ph 3 IMpower150 study (NCT02366143), 1L treatment (tx) with atezolizumab (A) + bevacizumab (B) + carboplatin + paclitaxel (CP; ABCP) significantly improved PFS and OS vs B + CP (BCP) in pts with chemotherapy-naive metastatic (met) nsq NSCLC. As pts with high tumor burden or large size (bulky disease) have poor survival outcomes, an exploratory analysis was conducted to determine whether pts with bulky disease in IMpower150 could derive benefit from ABCP. Methods: 1202 pts (ITT population) were randomized 1:1:1 to ABCP, atezo + CP (ACP) or BCP arms. Doses were given q3w: A, 1200 mg; B, 15 mg/kg; C, AUC 6 mg/mL/min; P, 200 mg/m2. Disease burden subgroups (high or low) were defined using the 3rd quartile of the sum of the longest diameter (SLD) of the target lesions or median number (no.) of met sites at baseline (BL). Exploratory efficacy analyses included PFS, OS, ORR, time to response (TTR) in these subgroups; safety was also assessed. Outcomes are reported for pts enrolled in the ABCP vs BCP arms. Results: Per 3rd quartile SLD (108 mm), 91 ABCP and 85 BCP pts had high disease burden. Per median no. of met sites (median = 2), 210 ABCP and 190 BCP pts had high disease burden. BL characteristics were generally balanced between ABCP and BCP in high disease burden subgroups. With a minimum follow-up of 32.4 mo (data cutoff: Sep 13, 2019), ABCP showed improved OS, PFS and ORR vs BCP in pts with high and low disease burden (Table). High disease burden did not impact TTR. The safety profile of ABCP was comparable between ITT-WT (no EGFR or ALK alterations) pts and high disease burden subgroups. Conclusions: A tx effect for OS, PFS and ORR was seen in pts with and without bulky disease when ABCP vs BCP was compared, regardless of the method used to define “bulky”; TTR was not affected in high disease burden pts. ABCP had a comparable safety profile in bulky disease and ITT-WT pts. ABCP may be a 1L tx option for pts with nsq NSCLC who have high disease burden. Clinical trial information: NCT02366143. [Table: see text]

Background Concordance between whole genome sequencing (WGS)/whole exome sequencing (WES) and circulating tumor DNA (ctDNA) is not known. Therefore, we studied concordance between matched WGS/WES and ctDNA in various solid tumors. In addition, we carried out an analysis of hotspot and actionable alterations in our data. Methods Retrospective analysis of 64 stage III/IV solid tumors (Gastrointestinal n = 20 Breast n = 12 Lung n = 19 Other n = 13) who underwent matched WGS/WES and ctDNA (77 genes) by commercially available platforms. Concordance was determined at patient and gene levels. Results Patient concordance between tissue and ctDNA results was 58% (n = 37). Concordance was higher when patients received systemic chemotherapy prior to tissue NGS and ctDNA compared to no chemotherapy (78% n = 21 Vs 43% n = 12, respectively p = 0.01) and positively correlated increasing tumor mutation burden. There was no significant difference in concordance when time interval between tissue NGS and ctDNA analysis was evaluated (55% n = 24 Vs 65% n = 13, =90 days respectively p = 0.20). Similarly, no statistical difference in concordance was found when tissue NGS was done on primary or metastatic sites (48% n = 12 Vs 64% n = 25, respectively p = 0.20). TMB positively correlated with the number of ctDNA mutations only in those who received chemotherapy (r(25)=0.74 p Conclusions Our analysis noted significant discordance between WGS/WES and ctDNA analysis. TMB and prior chemotherapy may affect concordance between NGS and ctDNA. Tissue NGS and ctDNA are complementary modalities and incorporating ctDNA with tissue NGS can increase the likelihood of capturing additional targetable alterations. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Lung cancer patients with activating EGFR mutations tend to respond poorly to IO, but this is not true for all activating mutation driven lung cancers. Recent data show that patients with BRAF mutations tend to respond better to IO. Our study estimated the tumor neoantigen burden in these tumors, and the likelihood of their presentation to cytotoxic T cells by estimating their binding affinity to major histocompatibility complex (MHC). Methods Whole exome data for 68 patients with EGFR mutant lung adenocarcinoma and 33 with BRAF mutations were extracted from the Cancer Genome Atlas. MAFTOOLs was used to determine the tumor mutational load. Nonamers were estimated by simulating possible nonamer neoantigens from MAF files. The neoantigen (MT) and wildtype (WT) binding affinities to MHC-I were calculated using the NetMHC 4.0 server. The differential binding affinity of the neoantigens in comparison to wildtype was calculated as mean differential agretopicity index (DAI) = WT - MT. Patient survival was estimated by the Kaplan-Meier method. Results Patients with mutated BRAF had higher median mutational burden (445, range 165-776) than those with EGFR mutations (90.5, range 60.5-219.5, p = 0.001). The median number of simulated neoantigens was higher in the BRAF (9536.5, range 3839.5-14626.0) vs the EGFR group (1895.5, range 1148.5-4766.5, p 1,000. No such survival benefit was identified in the EGFR mutant group (56% vs 58%, p = 0.81). Conclusions BRAF mutant lung cancers are characterized by higher neoantigen burden, but their neoantigen differential binding affinity to MHC-I complex was not different from EGFR mutant lung cancers. Our analysis suggests that the improved response to IO in the BRAF mutant population is due to increased quantity in neoantigen burden and not a qualitative difference in MHC-I binding. Further, DAI had a prognostic impact in the BRAF population suggesting that it may be a measure of tumor neoantigen immunogenicity. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure J. Subramanian: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Paradigm; Speaker Bureau / Expert testimony: Lilly; Research grant / Funding (institution): Biocept. All other authors have declared no conflicts of interest.

To understand the molecular differences between right-sided colon cancer (RCC), left-sided colon cancer (LCC) and rectal cancer, we analyzed colorectal tumors at the DNA, RNA, miRNA and protein levels using previously sequenced data from The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center. Clonal evolution analysis identified the same tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor dynamics and selection of downstream mutations were distinct in all three anatomical locations, with some similarities noted between LCC and rectal cancer. We found a potentially targetable alteration APC R1450* specific to RCC that has not been previously described. Differential gene expression analysis revealed multiple genes within the homeobox, G-protein coupled receptor binding and transcription regulation families were dysregulated in RCC, LCC, and rectal cancers and may have a pathological role in these cancers. Further, using a novel in silico proteomic analytic tool developed by our research group, we found distinct central or hub proteins with unique interactomes in each location. Protein expression signatures were not necessarily concordant with the tumor profiles obtained at the DNA and RNA levels, underscoring the relevance of post-transcriptional events in defining the biology of these cancers beyond molecular changes at the DNA and/or RNA level. Ultimately, not only tumor location and the respective genomic profile but also protein-protein interactions will need to be taken into account to improve treatment outcomes of colorectal cancers. Further studies that take into account the alterations found in this study may help in developing more tailored, and perhaps more effective, treatment strategies.Author summaryPatients with right-sided colon cancer (RCC) has a worse prognosis compared to left-sided colon cancer (LCC). Recent data has also shown that wild-type RAS metastatic RCC’s have poor outcomes when treated with the combination of chemotherapy and anti-EGFR therapy compared to LCC and rectal cancers. Therefore, There is an urgent unmet need to understand the molecular differences between RCC, LCC, and rectal cancers. In this study, we demonstrate clonal evolutionary trajectory and the order of mutations in RCC, LCC, and rectal cancers are distinct with some similarities between LCC and rectal cancers. The order of the mutations that lead to the acquisition of crucial driver alterations may have prognostic and therapeutic implications. We also discovered a novel targetable alteration, APC R1450* to be significantly enriched in early, late and metastatic RCC but not in LCC and rectal cancers. Amazingly, proteomic signatures were discordant with DNA and RNA levels. These distinct differences in DNA, RNA and post-transcriptional events may contribute to their unique clinicopathological features.Conflict of Interest StatementAshiq Masood Advisory board and speaker Bureau Bristol-Myers Squibb and Boehringer IngelheimJanakiraman Subramanian Advisory board - Astra Zeneca, Pfizer, Boehringer Ingelheim, Alexion, Paradigm, Bristol-Myers Squibb Speakers Bureau - Astra Zeneca, Boehringer Ingelheim, Lilly Research Support - Biocept and ParadigmArif Hussain Advisory board – Novartis, Bayer, Astra Zeneca Consultant – Bristol-Myers-Squibb All other authors have no conflict of interest.

Recent advances in next-generation sequencing have allowed for detailed molecular analysis of urothelial carcinomas, with potentially significant clinical implications for personalized treatment. Our objective in this review is to highlight studies from the past year that have furthered the understanding of urothelial cancer genomics.Recent studies by The Cancer Genome Atlas consortium further characterized urothelial carcinomas via molecular subtyping, and a schema was proposed to match each subtype with potential therapeutic implications. Molecular subtyping was also utilized in a separate analysis to determine which tumours benefit from neoadjuvant chemotherapy. Tumour characteristics were also explored pre and postneoadjuvant chemotherapy and a mutational signature associated with postcisplatin treatment was described. We also review a comprehensive analysis of upper tract urinary carcinomas published this past year.Recent genomic analyses have revealed that the classification of urothelial carcinoma is much more complex than the traditional dichotomy of nonmuscle-invasive and muscle-invasive bladder cancers. Molecular subtyping has provided additional insights into prognoses and treatment options for these patients. Although molecular subtyping is not yet ready for implementation into clinical practice, these latest efforts offer an exciting opportunity to integrate such information into prospective clinical studies that may ultimately lead to improved treatment outcomes.

Background Next generation sequencing tests (NGS) are usually performed on relatively small core biopsy or fine needle aspiration (FNA) samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform. Methods 2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed. Results 6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1-3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm2 provides a good margin of error for specimens to yield adequate drug association results. Conclusions Specimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform.

Patients demographics from TCGA. (DOCX 19 kb)

Methods section. (DOCX 52.9 kb)

Somatic mutation analysis  for RCC, LCC and rectal cancers. (DOCX 433 kb)

Background Next generation sequencing tests (NGS) are usually performed on relatively small core biopsy or fine needle aspiration (FNA) samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform. Methods 2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed. Results 6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1–3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm2 provides a good margin of error for specimens to yield adequate drug association results. Conclusions Specimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform.

Recent advances in Next Generation Sequencing (NGS) have provided remarkable insights into the genomic characteristics of human cancers that have spurred a revolution in the field of oncology. The mitogen-activated protein kinase pathway (MAPK) and its activating cell receptor, the receptor tyrosine kinases (RTKs), which together encompass the (RTK)-RAS-RAF-MEK-ERK axis, are central to oncogenesis. A pan-cancer genomics analysis presented in this review is made possible by large collaborative projects, including The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), and others. Landmark studies contributing to these projects have revealed alterations in cell signaling cascades that vary between cancer types and within tumors themselves. We review several of these studies in major tumor types to highlight recent advances in our understanding of the role of (RTK)-RAS-RAF alterations in cancer. Further studies are needed to increase the statistical power to detect clinically relevant low-frequency mutations, in addition to the known (RTK)-RAS-RAF pathway alterations, and to refine the resolution of the genomic landscape that defines these cancer mutations. The (RTK)-RAS-RAF-MEK-ERK mutation status, and their prognostic value, are also examined and correlated with clinical phenotypes. Treatments targeting various components of this pathway are ongoing, and are often effective initially in defined subgroups of patients. However, resistance to these agents can develop through adaptive mechanisms. With our steady increase in understanding the molecular biology of cancer, ongoing evaluation and monitoring through genomic analysis will continue to provide important information to the clinician in the context of treatment selection, response, resistance and outcomes.

Acute and chronic shortages of various pharmaceuticals and particularly of sterile injectable products are being reported on a global scale, prompting evaluation of more effective strategies to manage current shortages and development of new, high-quality pharmaceutical products to mitigate the risk of potential future shortages. Oncology drugs such as liposomal doxorubicin and 5-fluorouracil represent examples of first-choice drugs critically affected by shortages. Survey results indicate that the majority of hospitals and practicing oncologists have experienced drug shortages, which may have compromised patient safety and clinical outcomes, and increased health care costs, due to delays or changes in treatment regimens. Clinical trials evaluating novel agents in combination with standard-of-care drugs are also being affected by drug shortages. Clinical and ethical considerations on treatment objectives, drug indication, and availability of alternative options may help in prioritizing cancer patients involved in active drug shortages. The United States Food and Drug Administration and the European Medicines Agency have identified manufacturing problems, delays in supply, and lack of available active ingredients as the most frequent causes of recent or ongoing drug shortages, and have released specific guidance to monitor, manage, and reduce the risk of shortages. The upcoming loss of exclusivity for a number of anticancer biologics, together with the introduction of an abbreviated approval pathway for biosimilars, raises the question of whether these products will be vulnerable to shortages. Future supply by reliable manufacturers of well characterized biosimilar monoclonal antibodies, developed in compliance with regulatory and manufacturing guidelines and with substantial investments, may contribute to prevent future biologics shortages and ensure access to effective and safe treatment options for patients with cancer. Preclinical and clinical characterization is ongoing for potential biosimilars of trastuzumab, rituximab, and bevacizumab, with promising results.

Tumor heterogeneity, especially intratumoral heterogeneity, is a primary reason for treatment failure. A single biopsy may not reflect the complete genomic architecture of the tumor needed to make therapeutic decisions. Circulating tumor DNA (ctDNA) is believed to overcome these limitations. We analyzed concordance between ctDNA and whole-exome sequencing/whole-genome sequencing (WES/WGS) of tumor samples from patients with breast (n = 12), gastrointestinal (n = 20), lung (n = 19), and other tumor types (n = 13). Correlation in the driver, hotspot, and actionable alterations was studied. Three cases in which more-in-depth genomic analysis was required have been presented. A total 58% (37/64) of patients had at least one concordant mutation. Patients who had received systemic therapy before tissue next-generation sequencing (NGS) and ctDNA analysis showed high concordance (78% (21/27) vs. 43% (12/28) p = 0.01, respectively). Obtaining both NGS and ctDNA increased actionable alterations from 28% (18/64) to 52% (33/64) in our patients. Twenty-one patients had mutually exclusive actionable alterations seen only in either tissue NGS or ctDNA samples. Somatic hotspot mutation analysis showed significant discordance between tissue NGS and ctDNA analysis, denoting significant tumor heterogeneity in these malignancies. Increased tissue tumor mutation burden (TMB) positively correlated with the number of ctDNA mutations in patients who had received systemic therapy, but not in treatment-na&iuml, ve patients. Prior systemic therapy and TMB may affect concordance and should be taken into consideration in future studies. Incorporating driver, actionable, and hotspot analysis may help to further refine the correlation between these two platforms. Tissue NGS and ctDNA are complimentary, and if done in conjunction, may increase the detection rate of actionable alterations and potentially therapeutic targets.

8505 Background: Multi-lineage myelosuppression is an acute toxicity of cytotoxic chemotherapy leading to hematologic adverse events and dose reductions and delays. Current therapies are lineage specific and administered after chemotherapy damage.Trilaciclib (T), a highly selective, reversible CDK4/6 inhibitor, is designed to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy (myelopreservation). We have shown that T mitigates myelosuppression in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) receiving 1st-line chemotherapy. Methods: In this blinded, placebo-controlled, multicenter Phase 2 study, patients with previously treated ES-SCLC were randomized to T (240 mg/m2) + 0.75 mg/m2 topotecan, T (240 mg/m2) + 1.5 mg/m2 topotecan, or placebo (P) + 1.5 mg/m2 topotecan IV on days 1-5 of 21-day cycles. Patients had access to standard supportive care, except in cycle 1 where prophylactic growth factors were not allowed. Eligible patients had adequate organ function, measurable disease, ECOG PS 0-2, and disease progression during or after prior 1st/2nd-line chemotherapy. Objectives included safety, tolerability, measures of myelosuppression and tumor efficacy. Results: 91 patients were randomized: 30 patients received T + 0.75 mg/m2 topotecan, 32 patients received T + 1.5 mg/m2 topotecan and 28 patients received P + 1.5 mg/m2 topotecan. In patients receiving 1.5 mg/m2 topotecan, T treatment reduced occurrence [40.6% (T) vs 75.6% (P), p = 0.016], and duration in cycle 1 [2 days (T) vs 8 days (P), p = < 0.0001] of severe neutropenia. T-treated patients had fewer RBC transfusions on/after 5 weeks on study, GCSF administrations, and all-cause dose reductions. Chemotherapy efficacy was comparable in both arms (P and T) treated with 1.5 mg/m2 topotecan (median PFS (T) 4.2 months vs (P) 4.2 months, HR = 0.83). OS data is immature. Conclusions: T combined with topotecan mitigated chemotherapy-induced myelosuppression and improved tolerability of topotecan vs P. Results suggest the addition of T to cytotoxic chemotherapy for the treatment of ES-SCLC is clinically beneficial. Clinical trial information: NCT02514447.

e14268 Background: Checkpoint inhibitor-based immunotherapy has varying success among tumor types and patients. Predictive biomarkers are in high demand to assist with patient selection. Responses to these agents are correlated with programmed cell death ligand 1 (PD-L1) expression, microsatellite instability (MSI), and tumor mutational burden (TMB). Here we evaluated PD-L1 expression, MSI status and TMB in a variety of solid tumors to determine their relationships. Methods: A total of 109 specimens were identified in patients diagnosed with solid tumors that underwent a Paradigm Diagnostic Cancer Test. MSI scores were determined by the number of indels present in runs of 6 homopolymer bases per megabase, with a cut-off of 6 to distinguish between MSI-high (MSI-H) and MSI-stable (MSI-S). TMB scores greater than or equal to 10 muts/Mb were designated as high (TMB-H). Results: Of all tumors, 19.3% were MSI-high. PD-L1 testing was performed in 71.5% of all samples; of these, 21.8% were PD-L1 positive. TMB scores of PD-L1 positive tumors (mean = 10.3 muts/Mb) and PD-L1 negative tumors (mean = 8.6 muts/Mb) did not differ significantly (p = 0.57). All MSI-H tumors were TMB-H, and MSI-H tumors had higher mean TMB scores than MSI-S tumors (57 muts/Mb versus 7.6 muts/Mb; p = 0.06). Among TMB-H tumors, MSI-H status was associated with higher TMB scores compared to MSI-S tumors (55.2 muts/Mb versus 22.1 muts/Mb, p = 0.18). Of the both MSI-S and TMB-H tumors, 68.8% were lung cancers and 18.8% were breast cancers. Tumors both MSI-H and TMB-H were 47.6% gastrointestinal carcinomas and 33.3% endometrial carcinomas. Conclusions: In our analysis, TMB was independent of PD-L1 status. All MSI-H tumors were also TMB-H; these were primarily gastrointestinal and endometrial carcinomas whereas TMB-H tumors that were MSI-S consisted predominantly of lung cancers. This difference may be due to the different mechanisms of acquiring mutations during carcinogenesis in these two tumor types. These data also highlight the need for integrated PD-L1, MSI and TMB testing to identify potential responders to immunotherapy.

Tobacco smoking is the most common cause of lung cancer, but approximately 10-25% of patients with lung cancer are life-long never smokers. The cause of lung cancer in never smokers is unknown, although tobacco-smoke exposure may play a role in some of these patients. Lung cancer that develops in the absence of significant tobacco-smoke exposure appears to be a unique disease entity with novel genomic and epigenomic alterations and activation of molecular pathways that are not generally seen in tobacco-smoke-induced lung cancer. These molecular alterations are very likely responsible for the unique clinico-pathological features of lung cancer in never smokers (LCINS), and some of these molecular alterations - such as the activating EGFR TK mutations and EML4-ALK fusion - significantly influence therapeutic choices and treatment outcomes. In the last few years there has been a number of studies exploring the molecular characteristics of LCINS, and some of them have reported new and significant findings. Here we review the key findings from these studies and discuss their potential therapeutic implications.

IntroductionClinical research in non–small-cell lung cancer (NSCLC) is a rapidly evolving field. In an effort to identify the current trends in lung cancer clinical research, we reviewed ongoing clinical trials in NSCLC listed in the ClinicalTrials.gov registry in 2012, and we also compared this data to a similar survey conducted by us in 2009.MethodsThe Web site's advanced search function was used to search for the term “non-small cell lung cancer.” The search was further refined by using the following options from the search page drop-down menu, “open studies” and “interventional.” Studies with non-NSCLC tumor histologies and pediatric studies were excluded.ResultsOf the 477 trials included in the analysis, 105 (22.0%) were phase I, 223 phase II (46.8%), and 63 phase III trials (13.2%). When compared with data from 2009, university-sponsored trials decreased in number (45.4%–34.2%; p < 0.001) whereas industry-sponsored trials remained almost the same. There was a significant increase in trials conducted exclusively outside of the United States (35.9%–48.8%; p = 0.001). The number of studies with locations in China (61, 12.8%) was second only to that in the United States (244, 51.2%). Studies reporting biomarker analysis increased significantly from 37.5% to 49.1% in 2012 (p < 0.001). Biomarker-based patient selection also increased significantly from 7.9% to 25.8% (p < 0.001). Targeted therapies were evaluated in 70.6% of phase I/II and II trials, and the most common class of targeted agent studied was epidermal growth factor receptor tyrosine kinase inhibitors (38.0%). Prespecified accrual times were observed to increase when compared with data reported in 2009, especially among industry-sponsored studies.ConclusionsOur survey identified major changes in lung cancer clinical research since 2009. Almost half of all studies registered at the ClinicalTrials.gov Web site are being conducted outside the United States, and several novel molecularly targeted agents are being evaluated in the treatment of patients with NSCLC. More importantly, we identified a threefold increase in the number of studies that perform biomarker testing to determine patient selection over the last 3 years.

BackgroundIncreased tumor size is a known risk for poor outcomes in patients with stage I and II non–small cell lung cancer (NSCLC), who are treated with surgery or radiotherapy. However, there is limited information regarding the impact of tumor size on the outcomes of patients with mediastinal lymph node involvement. We conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis to evaluate the prognostic significance of tumor size in patients with unresected stage III NSCLC.MethodsThe SEER registry was queried for patients with unresected NSCLC stage III and no malignant pleural effusion, aged 21 years or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1–3cm), S2 (3.1–5cm), S3 (5.1–7cm), and S4 (7.1–20cm). Demographic variables included age, sex, race and histology. Overall survival (OS) and disease-specific survival (DSS) were estimated by the Kaplan–Meier method, and the Cox proportional hazard model was used to evaluate whether tumor size remained an independent risk factor in multivariable analysis.ResultsA total of 12,315 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were men (58.7%) and white (81.3%). Tumor size was an independent predictor for both OS (p < 0.0001) and DSS (p < 0.001) in all subgroups of patients.ConclusionTumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC, and should be considered in the stratification of patients treated in this setting after validation of this finding in additional studies.

SummaryWe report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs.

Background This trial focused on optimally combining existing targeted therapies and cytotoxic chemotherapy in the treatment of unselected patients with advanced non–small-cell lung cancer (NSCLC). Methods Patients with previously untreated advanced-stage nonsquamous NSCLC were eligible for this trial. In module A, patients received up to 4 cycles of erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks. Patients then received carboplatin (AUC = 6), paclitaxel 200 mg/m2, and bevacizumab 15 mg/kg for 4 cycles in module B. Patients who did not have progressive disease in module A received maintenance erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks in module C. Results Forty-eight patients were enrolled in this multicenter phase II trial. Most patients were male (62.5%) and white (77.1%) with stage IV disease (93.8%) and adenocarcinoma histologic type (66.7%). The overall response rate in module A was 10.4%, in module B it was 15.1%, and in module C it was 5.5%. The study achieved its primary endpoint, with a nonprogression rate of 45.8% in module A. The median overall survival (OS) was 12.6 months. Conclusion The novel systemic therapy regimen is feasible in patients with advanced NSCLC. However there is no further role for developing this regimen in unselected patients with NSCLC.

A number of novel agents are currently being tested in clinical trials in patients with cancer. Results from early-phase trials, often in unselected groups of patients with a wide variety of cancer types, were reported at the 46th annual meeting of the American Society of Clinical Oncology (ASCO). We report on selected studies from the developmental therapeutics track (abstracts 2500-2613 and 3000-3108) that may be of interest to the thoracic oncology community.

Globally, lung cancer remains the most common cause of cancer-related death. In recent years, it has become clear that development of rational molecular targeted therapies is critical to improve the outcomes of patients with lung cancer. A better understanding of the tumor biology is crucial to achieve this goal. Several new findings in the field of tumor biology were presented at the 46th Annual Meeting of the American Society of Clinical Oncology. Novel genetic mutations were identified in pleural mesothelioma using array-based technologies. Several studies on the development and testing of new molecular diagnostic tests to detect epidermal growth factor receptor tyrosine kinase mutations and EML4-ALK (Echinoderm Microtubule-associated Protein like 4 Anaplastic Lymphoma Receptor Tyrosine Kinase) fusion gene were presented as well.

Angiogenesis is essential for cancer growth and progression. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis. The addition of bevacizumab, an antibody to vascular endothelial growth factor (VEGF), to paclitaxel and carboplatin improves survival compared with chemotherapy alone in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) are a new class of drugs that target the TK domain of the VEGF receptors. To evaluate the role of this class of agents in the treatment of NSCLC, some phase II and phase III studies using these agents alone or in combination with other agents have been completed. This review summarizes the currently available data on VEGFR TKIs in the treatment of NSCLC.

Introduction Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future. Methods We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older." Results Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection. Conclusions Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.

Introduction: TSR-042 is a humanized monoclonal antibody targeting programmed death (PD)-1, effectively blocking interaction with its ligands PD-L1 and PD-L2. TSR-042 is being evaluated in patients (pts) with advanced solid tumors in the ongoing phase 1 GARNET trial (NCT02715284). Weight based dose escalation (Part 1) and fixed-dose safety studies (Part 2A) have been completed,1 and the study is currently enrolling pts with specific tumor types into expansion cohorts. Here, we present safety and efficacy data from the microsatellite instability-high (MSI-H) endometrial cancer (EC) and non-small cell lung cancer (NSCLC) cohorts, as well as pharmacokinetic (PK) and receptor occupancy (RO) characterization at the recommended phase 2 dose (RP2D). Methods/Procedures: 30 NSCLC pts and 19 MSI-H EC pts with previously treated recurrent or advanced disease were enrolled; median number of prior lines of therapy for metastatic disease was 1.0 for both cohorts. MSI status for EC pts was determined centrally using a next generation sequencing-based assay. Key exclusion criteria included prior therapy with agents targeting anti-PD-1, PD-L1, or PD-L2, and uncontrolled CNS metastases. Pts were treated at the R2PD of TSR-042: 500 mg Q3W for the first 4 cycles and 1000 mg Q6W thereafter. Serum and PBMCs were collected for PK and RO analyses, respectively. Antitumor activity was assessed by investigators using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). RO was assessed using a CD3+ binding assay (direct receptor occupancy).1 Results: Among the 30 NSCLC and 19 MSI-H EC pts, 42 (85.7%) pts reported ≥1 adverse event (AE), with grade ≥3 AEs reported in 13/49 (26.5%) pts. The most common AEs were diarrhea and nausea (11 pts each), arthralgia and fatigue (9 pts each), and cough, decreased appetite, and dyspnea (7 pts each). 25/49 (51.0%) pts reported treatment-related AEs; 11/49 (22.4%) pts had serious AEs; 1 case of grade 3 fatigue and 1 case of grade 3 leukopenia and grade 3 neutropenia were deemed treatment-related. 21 NSCLC and 11 MSI-H EC pts had at least 1 tumor assessment. Among NSCLC pts, 7/21 (33.3%) had a partial response (irPR; confirmed and unconfirmed), and 6/21 (28.6%) had stable disease (irSD); among MSI-H EC pts, 4/11 (36.4%) had irPR, and 2/11 (18.2%) had irSD. TSR-042 demonstrated dose-proportional PK. The maximal achievable RO was observed in pts treated at the RP2D, consistent with the results reported for Parts 1 and 2A.1 Conclusions: These results indicate clinical benefit of TSR-042 in previously treated NSCLC and MSI-H EC patients, with a safety profile similar to other PD-1 inhibitors. PK results were consistent across all patients evaluated and show that maximal achievable receptor occupancy was attained at the RP2D. 1. Sachdev JC et al. Ann Oncol. 2017(suppl 5):28:420;1185P Citation Format: Victor Moreno, Maria-Pilar Barretina-Ginesta, Wei Guo, Sharon Lu, David Jenkins, Kristen McEachern, Vienna Reichert, Steven Dunlap, Ellie Im, Lucy Gilbert, Ana Oaknin, Charles Leath, III, Janakiraman Subramanian. Preliminary safety, efficacy, and PK/PD characterization from GARNET, a phase 1 clinical trial of the anti-PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced NSCLC and MSI-H endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT053.

e18088Background: Concurrent chemotherapy with definitive radiation is the standard of care treatment for locally advanced NPC. However, there is limited data on the optimal management of stage II ...

3592Background: Right-sided (RCC) and left-sided colon cancers (LCC) have different clinical/biological characteristics. Comprehensive genomic analysis (Whole exome/genome, Copy number, RNA, MicroR...

e21235Background: The median age at diagnosis of lung cancer is 70 years, and prospective studies have shown clear survival benefit for chemotherapy in elderly patients. However there are limited d...

12123Background: Squamous cell carcinomas (SCC) of the lung, esophagus and head and neck (H&N) are indistinguishable by histology. Data from large-scale genomic studies have identified significant ...

e24291Background: Tumor profiling by next-generation sequencing (NGS) to identify actionable somatic alterations is the cornerstone of precision oncology. Using this information oncologists can mat...

1558Background: Screening high risk patients for lung cancer with Low Dose Computed Tomography (LDCT) reduces lung cancer-specific mortality, however its adoption in routine clinical care has been ...

Background: Sapacitabine is a novel oral nucleoside analogue with a unique ability to induce single-strand DNA breaks after incorporation into DNA, leading to production of double-strand DNA breaks and/or G2 cell cycle arrest. In AML cell lines, the active metabolite of sapacitabine, CNDAC, is synergistic with hypomethylating agents (HMAs) particularly when treated with HMAs first. In a pilot study, there were 6 CRs and 2 PRs in 25 patients treated with sapacitabine in alternating cycles with decitabine. This global randomized phase 3 study evaluated the survival benefit of this treatment strategy vs. decitabine monotherapy. Methods: Decitabine 20 mg/m2 was administered intravenously daily x 5 days of a 4-week cycle (for the control arm and odd cycles of the study arm) alternating with sapacitabine 300 mg p.o. b.i.d. x 3 days/week x 2 weeks of a 4-week cycle (even cycles of the study arm). The safety of these doses was further evaluated in the lead-in phase of the phase 3 study to confirm the findings from the pilot study. Eligible patients were ≥70 years with untreated AML and unsuitable for or unwilling to receive standard induction chemotherapy. Patients who had received HMAs for prior MDS or MPD were excluded. Results: For 482 patients randomized to receive decitabine/sapacitabine (n=241) vs. decitabine only (n=241), randomization was stratified by the presence of antecedent MDS or MPN, peripheral white blood cell count (WBC 40,000 in 59 patients (12%); 194 patients (40%) had unfavorable cytogenetic risk by SWOG criteria. Disease characteristics were well balanced in both arms. In total, 13.7% of patients achieved CR, more on the study arm vs. control (16.6% vs. 10.8%). A total of 37.3% treated patients received ≥5 cycles of treatment, similar on both arms, as were 30- and 60-day death rates. Median overall survival was 5.9 months on the study arm vs. 5.7 months on control arm, which did not reach a statistically significant difference. In the subgroup of patients with 10% patients were thrombocytopenia, anemia, neutropenia, pneumonia, febrile neutropenia, sepsis, and disease progression. Conclusion: The regimen of sapacitabine administered in alternating cycles with decitabine was active and well tolerated but it did not significantly improve overall survival as compared to decitabine monotherapy. Further analyses are being conducted to characterize the subgroups of patients who appeared to have benefited from this treatment regimen and the potential cost savings associated with the use of an oral drug. Disclosures Kantarjian: Amgen: Research Funding; Pfizer: Research Funding; Delta-Fly Pharma: Research Funding; ARIAD: Research Funding; Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding. Goldberg: Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; COTA: Employment, Equity Ownership; Pfizer: Honoraria; Ariad: Speakers Bureau; Jazz: Speakers Bureau. Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees. Strickland: Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy; CTI BioPharma: Consultancy; Tolero Pharmaceuticals: Consultancy; Sunesis Pharamaceuticals: Consultancy, Research Funding; Baxalta: Consultancy; Alexion Pharmaceuticals: Consultancy; Astellas Pharma: Honoraria. Rubenstein: Alexion Pharmaceuticals: Speakers Bureau. Arellano: Cephalon Oncology: Research Funding. Schiller: bluebird bio: Research Funding; mateon therapeutics: Research Funding. Gaidano: Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Montesinos: Celgene Corporation: Honoraria, Research Funding. Rizzieri: Shire: Research Funding; Erytech: Research Funding. Subramanian: Boehringer-Ingelheim, Lilly, BMS, Astra-Zeneca, Pfizer, Biocept: Consultancy, Speakers Bureau. Buyse: IDDI: Employment, Equity Ownership. Chiao: Cyclacel LTD: Employment, Equity Ownership.

Background Although there has been a significant survival improvement for patients with metastatic NSCLC enrolled in randomized trials, it is not clear whether a similar benefit is seen in an unselected group of patients. Therefore, we conducted a study to evaluate for survival changes in a large national cancer registry database. Patients and Methods The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients with NSCLC stage IV, aged 21 years or older, and diagnosed between 1990 and 2005. We analyzed four equally divided time periods between 1990 and 2005 (1990 to 1993 or period 1, 1994 to 1997 or period 2, 1998 to 2001 or period 3, and 2002 to 2005 or period 4) to determine changes in overall survival for all patients and according to histology. Results We identified 129,337 patients meeting eligibility criteria. There was a significant improvement in overall survival since period 1. One-year and 2-year overall survival increased from 13.2 and 4.5%, respectively, in period 1 to 19.4% and 7.8%, respectively, in period 4. On multivariate analysis, survival for adenocarcinoma was increased compared with squamous cell carcinoma only in period 4 ( p = 0.02). Conclusions There has been a modest but statistically significant improvement in overall survival for stage IV NSCLC over the past 16 years. The recent differences in outcomes based on histology observed in period 4 may reflect the increased activity of epidermal growth factor receptor tyrosine kinase inhibitors in adenocarcinoma compared with squamous cell carcinoma.

Background Tobacco smoking leads to lung cancer. Approximately 10% of patients with lung cancer are life long never-smokers. There are only limited data available on the clinical characteristics and outcomes of lung cancer in never-smokers from the Western hemisphere. Methods Demographic and survival information was collected on 254 never-smokers with a confirmed pathologic diagnosis of non-small cell lung cancer (NSCLC) by reviewing their medical records and the Social Security database. Results The study population consisted of 182 (71.6%) women and 72 (28.3%) men. The median age was 70 years (range: 31–91 years). Adenocarcinoma was the most common histology accounting for 60.8% of all patients, followed by NSCLC not otherwise specified (14.4%), bronchoalveolar carcinoma (13.6%), squamous cell carcinoma (8.8%), and large-cell type (2.4%). Majority of patients presented with stage III or IV disease (62.5%). We compared survival between never-smokers and smokers with NSCLC matched for gender, histology, tumor stage, and years of diagnosis. No significant difference in 5-year survival was seen between never-smokers (27.2%) and smokers with NSCLC (31.3%; p = 0.73). Conclusions Two thirds of patients with lung cancer who report no history of tobacco smoking are women. In the matched case–control analysis, we report no significant survival difference between lung cancer in never-smokers and those with history of tobacco smoking and lung cancer.

Lung cancer is the leading cause of cancer-related death in the United States. Although tobacco smoking accounts for the majority of lung cancer, approximately 10% of patients with lung cancer in the United States are lifelong never smokers. Lung cancer in the never smokers (LCINS) affects women disproportionately more often than men. Only limited data are available on the etiopathogenesis, molecular abnormalities, and prognosis of LCINS. Several etiologic factors have been proposed for the development of LCINS, including exposure to radon, cooking fumes, asbestos, heavy metals, and environmental tobacco smoke, human papillomavirus infection, and inherited genetic susceptibility. However, the relative significance of these individual factors among different ethnic populations in the development of LCINS has not been well-characterized. Adenocarcinoma is the predominant histologic subtype reported with LCINS. Striking differences in response rates and outcomes are seen when patients with advanced non–small-cell lung cancer (NSCLC) who are lifelong never smokers are treated with epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors such as gefitinib or erlotinib compared with the outcomes with these agents in patients with tobacco-associated lung cancer. Interestingly, the activating mutations in the EGFR-TK inhibitors have been reported significantly more frequently in LCINS than in patients with tobacco-related NSCLC. This review will summarize available data on the epidemiology, risk factors, molecular genetics, management options, and outcomes of LCINS.

The nine papers selected for the "best of the month" cover a broad range of topics including adjuvant therapy, targeted therapy with epidermal growth factor or vascular endothelial growth factor inhibitors, surgical approaches to lung cancer, and use of genomic profiles.