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In a large academic medical center, processes for ordering and receiving biomarker testing to inform cancer treatment in non–small cell lung cancer varied by whether tests were conducted internally or externally. Lack of standardization in biomarker testing processes, despite the availability of electronic health record solutions, contributes to clinician burden and may increase risk of delays in receipt of testing results; therefore, efforts to streamline ordering processes may benefit health systems. [ABSTRACT FROM AUTHOR]

Background: KRAS mutation‐positive (KRAS‐positive), advanced nonsmall‐cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are extremely heterogeneous from a biologic point of view, and real‐world data by mutation subtype in the era of immunotherapy are still incomplete. Methods: The objective of this study was to retrospectively analyze all consecutive patients with advanced/metastatic, KRAS‐positive NSCLC who were diagnosed at a single academic institution since the advent of immunotherapy. The authors report on the natural history of the disease as well as the efficacy of first‐line treatments in the entire cohort and by KRAS mutation subtypes as well as the presence/absence of co‐mutations. Results: From March 2016 to December 2021, the authors identified 199 consecutive patients who had KRAS‐positive, advanced or metastatic NSCLC. The median overall survival (OS) was 10.7 months (95% confidence interval [CI], 8.5–12.9 months), and there were no differences by mutation subtype. Among 134 patients who received first‐line treatment, the median OS was 12.2 months (95% CI, 8.3–16.1 months), and the median progression‐free survival was 5.6 months (95% CI, 4.5–6.6 months). At multivariate analysis, only an Eastern Cooperative Oncology Group performance status of 2 was associated with significantly shorter progression‐free survival and OS. Conclusions: KRAS‐positive, advanced NSCLC is characterized by a poor prognosis despite the introduction of immunotherapy. Survival was not associated with KRAS mutation subtype. Plain Language Summary: This study evaluated the efficacy of systemic therapies for advanced/metastatic nonsmall cell lung cancer harboring KRAS mutations, along with the potential predictive and prognostic role of mutation subtypes. The authors found that advanced/metastatic, KRAS‐positive nonsmall cell lung cancer is characterized by a poor prognosis and that first‐line treatment efficacy is not related to different KRAS mutations, although a numerically shorter median progression‐free survival was observed in patients who had p.G12D and p.G12A mutations.These results underline the need for novel treatment options in this population, such as next‐generation KRAS inhibitors, which are in clinical and preclinical development. Despite the introduction of immunotherapy, KRAS‐positive, advanced non–small cell lung cancer is still characterized by a poor prognosis. In this study, KRAS mutation subtypes did not influence survival. [ABSTRACT FROM AUTHOR]

Background: This study evaluated whether an addition of bevacizumab to erlotinib improves clinical outcomes in patients with advanced EGFR‐mutated non–small cell lung cancer (NSCLC). Methods: This is an open‐label, multicenter, randomized Phase 2 study in South Korea. Chemonaïve patients with Stage IIIB/IV NSCLC with EGFR 19 deletion or L858R mutation were eligible. Asymptomatic brain metastasis (BM) was enrolled without local treatment. Patients received either erlotinib plus bevacizumab or erlotinib. Results: Between December 2016 and March 2019, 127 patients were randomly assigned to receive erlotinib plus bevacizumab (n = 64) or erlotinib (n = 63). Fifty‐nine (46.5%) patients had baseline BM. Fewer patients in the erlotinib plus bevacizumab arm received radiotherapy for BM than in the erlotinib arm (10.3% vs. 40.0%). A trend toward longer progression‐free survival (PFS) was observed in the erlotinib plus bevacizumab arm compared with the erlotinib alone arm; however, it was not statistically significant (median PFS, 17.5 months vs. 12.4 months; hazard ratio [HR], 0.74; 95% CI, 0.51–1.08; p =.119). The unplanned subgroup analysis showed a longer PFS with erlotinib plus bevacizumab in patients with BM (median PFS, 18.6 months vs. 10.3 months; HR, 0.54; 95% CI, 0.31–0.95; p =.032). Grade 3 or worse adverse events occurred in 56.6% of the erlotinib plus bevacizumab arm and 20.6% of the erlotinib arm. Conclusions: Although it was not statistically significant, a trend to improvement in PFS was observed in patients with erlotinib plus bevacizumab compared to erlotinib alone. Plain Language Summary: A randomized Phase 2 study compared erlotinib with or without bevacizumab in previously untreated patients with advanced non–small cell lung cancer with EGFR mutation. The erlotinib plus bevacizumab failed to improve median progression‐free survival compared with the erlotinib alone. However, the progression‐free survival benefit from erlotinib plus bevacizumab was found in patients with brain metastasis with no severe hemorrhagic adverse effects. A trend to improvement in progression‐free survival was observed in patients with advanced EGFR‐mutated non–small cell lung cancer treated with erlotinib plus bevacizumab compared with erlotinib alone. The progression‐free survival benefit from erlotinib plus bevacizumab was most significant in patients with brain metastasis with no severe hemorrhagic adverse effects. [ABSTRACT FROM AUTHOR]

Plain language summary: DNA is the sequence that codes for proteins.Messenger RNA is transcribed from the DNA sequence of genes and translated into protein.It can be difficult to predict how a change in the DNA sequence will affect messenger RNA and protein quantity and quality.DNA translocation changes can cause the joining of sequences from two different genes or different parts of the same gene.DNA sequencing is often used clinically to predict how DNA changes might affect proteins.Alternatively, RNA sequencing can be used as a more direct measure of the effect of DNA changes on the protein products.This sequencing is important for identifying changes in cancer that may indicate response to targeted therapy, prognosis, or diagnosis. RNA sequencing provides insight into the qualitative and quantitative effects of DNA changes on the encoded protein. Targeted RNA sequencing can identify driver mutations, fusions, and splice variants and also can detect changes in gene expression that may correspond to changes in protein amount. [ABSTRACT FROM AUTHOR]

Background: The objective of this phase 2 trial was to assess the efficacy and safety of induction bevacizumab plus chemotherapy followed by surgery in patients with unresectable stage III lung adenocarcinoma.Methods: The authors investigated induction bevacizumab (7.5 mg/kg) plus pemetrexed (500 mg/m(2) and carboplatin (area under the receiver operating characteristic curve = 5) followed by surgery for patients with unresectable stage III lung adenocarcinoma ages 18 to 65 years. The patients received neoadjuvant therapy every 3 weeks for 4 cycles. Surgery was scheduled 3 to 4 weeks after the last neoadjuvant therapy; then, the medical team assessed each patient's resectability status. The primary endpoint was the resectability rate.Results: From April 2012 to April 2014, 42 patients were enrolled and received bevacizumab plus pemetrexed and carboplatin. Grade 3 or 4 induction-related AEs included fatigue in 5 patients, neutropenia in 4 patients, hypertension in 1 patient, anemia in 1 patient, and thrombocytopenia in 1 patient. One patient achieved a complete response, 22 achieved a partial response, 17 had stable disease, and 2 had progressive disease. After neoadjuvant therapy, 31 patients (73.8%) underwent surgery, including 11 who underwent pneumonectomy. Complete (R0) resection was achieved in 22 patients (52.4%). Reoperation was required in 1 patient because of a bleeding intercostal artery. No perioperative thromboembolic events or wound-healing problems were observed. The median event-free survival was 15.4 months, and the 1-year event-free survival rate was 56.1%.Conclusions: Treatment with neoadjuvant bevacizumab in combination with pemetrexed and carboplatin followed by surgery appears to be feasible and safe in patients with unresectable stage III lung adenocarcinoma. Cancer 2016;122:740-747. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging-positron emission tomography (MRI-PET) would increase the number of correctly upstaged patients compared with WB PET-computed tomography (PET-CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC). METHODS: From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI-PET or WB PET-CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging. RESULTS: Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI-PET group and in 26 of 120 patients (21.7%) in the PET-CT plus brain MRI group (4.2% difference; 95% confidence interval, −6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI-PET group and in 7 of 120 patients (5.8%) in the PET-CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%-20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (−10.7% difference; 95% confidence interval, −20.1% to −1.4%; P = .022). CONCLUSIONS: Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI-PET did not appear to help identify significantly more correctly upstaged patients than PET-CT plus brain MRI in patients with NSCLC. Cancer 2013. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chemoprevention for lung cancer with nutraceutical or anti-inflammatory agents has had mixed clinical benefit. Novel targeted agents hold the promise of greater efficacy and selectivity. The authors of this report evaluated enzastaurin, a selective protein kinase C-β (PKC-β) inhibitor with antiproliferative and proapoptotic properties, in former smokers. METHODS: The primary objective of this study was to compare the average fraction of Ki-67-stained cells (the Ki-67 labeling index [LI]) in bronchial biopsy specimens that were collected before and after treatment. Participants were randomized (2:1) to receive either 6 months of daily oral enzastaurin (500 mg) or placebo. Stratification was based on morphology, history of lung cancer, and airway obstruction. RESULTS: In pretrial investigations, the rationale for PKC-β inhibition and pathway interrogation was established in premalignant lesions and early stage lung cancer. In an intent-to-treat analysis, of 40 randomized participants, there was no significant difference in the pretreatment/post-treatment change in the Ki-67 LI between the enzastaurin group and the placebo group ( P = .53). Six participants discontinued enzastaurin, including 4 participants who had adverse events, including abdominal distension, deep vein thrombosis, hyponatremia, and rash, and 2 participants who decided to discontinue. One participant in the placebo group was discontinued on the study because of noncompliance. Two participants had ≥1 serious adverse event (bradycardia, deep vein thrombosis, and hypotension). CONCLUSIONS: To the authors' knowledge, this represents the first chemoprevention trial with a non-US Food and Drug Administration-approved, oral, small-molecule-targeted agent. Although the primary endpoint was not met, enzastaurin was tolerable for 6 months by 75% of participants, and there was a suggestion of response in a subset analysis that was restricted to those who had metaplastic or dysplastic lesions. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lung adenocarcinomas can be distinguished by identifying mutated driver oncogenes, including epidermal growth factor receptor ( EGFR) and KRAS. Mutations in EGFR are associated with both improved survival as well as response to treatment with erlotinib and gefitinib. However, the prognostic significance of KRAS has not been evaluated in large numbers of patients and remains controversial. For the current report, the authors examined the association of EGFR and KRAS mutations with survival among patients with advanced lung adenocarcinomas. METHODS: Data were analyzed from patients with advanced lung adenocarcinomas who had known EGFR and KRAS mutation status evaluated between 2002 and 2009. The collected clinical variables included age, sex, Karnofsky performance status, smoking history, and treatment history. Overall survival from the diagnosis of advanced disease was analyzed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: In total, 1036 patients were evaluated, including 610 women (59%) and 344 never-smokers (33%). The median patient age was 65 years (range, 25-92 years), and the majority of patients (81%) had a Karnofsky performance status ≥80%. In multivariate analysis, EGFR mutations were associated with longer overall survival (hazard ratio, 0.6; P < .001), and KRAS mutations were associated with shorter survival (hazard ratio, 1.21; P = .048). CONCLUSIONS: KRAS mutations predicted shorter survival for patients with advanced lung adenocarcinomas. The presence of EGFR and KRAS mutations define distinct subsets of patients with lung adenocarcinomas and should be determined in patients when they are diagnosed with advanced disease. Clinical trial reports should include EGFR and KRAS mutation status along with other prognostic factors. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gefitinib was compared with pemetrexed as second-line therapy in a clinically selected population previously treated with platinum-based chemotherapy. METHODS: A phase 3 trial of gefitinib (250 mg/day) versus pemetrexed (500 mg/m2 on day 1, every 3 weeks) was conducted in patients who had never smoked and who had advanced pulmonary adenocarcinoma treated with 1 previous platinum-based regimen. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 135 patients were analyzed. The gefitinib group had significantly longer PFS compared with the pemetrexed group, with a median PFS time of 9.0 versus 3.0 months ( P = .0006). The objective response rates were 58.8% and 22.4% for gefitinib and pemetrexed, respectively ( P < .001). However, there was no statistically significant difference in overall survival between the 2 groups (22.2 vs 18.9 months; P = .37). The difference of PFS was increased in a subgroup analysis of 33 patients with activating epidermal growth factor receptor mutation (15.7 vs 2.9 months; hazard ratio, 0.3; 95% confidence interval, 0.13-0.72; P = .005), with numerical superiority of gefitinib in the 38 patients testing negative for epidermal growth factor receptor mutation (5.9 vs 2.7 months; P = .099). Both regimens were well tolerated. There were no significantly different changes in quality of life between the 2 groups, except that symptom scores for dyspnea and diarrhea favored the gefitinib and pemetrexed arms, respectively. CONCLUSIONS: Gefitinib showed superior efficacy to pemetrexed as second-line therapy in Korean never-smokers with pulmonary adenocarcinoma. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The authors previously demonstrated that never-smokers with stage IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and sex. In this study, the authors hypothesized that smoking-dependent differences in the distribution of driver mutations may explain differences in prognosis between these subgroups. METHODS: In total, 293 never-smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor ( EGFR) mutations and v-Ki- ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS) mutations and rearrangements in anaplastic lymphoma kinase ( ALK) between 2009 and 2010 were investigated. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method. Group comparison was performed with log-rank tests and Cox proportional hazards methods. RESULTS: Although the overall incidence of these mutations was nearly identical (55% never-smokers vs 57% current/former smokers; P = .48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never-smokers vs 14% former/current smokers; P < .0001), KRAS mutations (4% never-smokers vs 43% former/current smokers; P < .0001), and ALK rearrangements (12% never-smokers vs 2% former/current smokers; P < .0001). Among never-smokers and former/current smokers, the prognosis differed significantly by genotype. Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype. CONCLUSIONS: Never-smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Amplification of the mesenchymal-epithelial transition factor ( MET) gene can promote tumor resistance to epidermal growth factor receptor (EGFR) inhibition. Dual EGFR-MET inhibition may overcome this resistance. Tivantinib (ARQ 197) is a selective, oral, non-ATP-competitive, small-molecule inhibitor of the MET receptor tyrosine kinase. This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of tivantinib combined with the EGFR inhibitor erlotinib. METHODS: Patients with advanced solid malignancies were administered oral tivantinib at escalating doses of 120, 240, 360, and 480 mg twice daily (BID) plus 150 mg erlotinib once daily (QD). Single or multiple intrapatient dose escalation was planned in the absence of dose-limiting toxicity in the first cycle of therapy (21 days). RESULTS: Thirty-two patients received combination treatment. Tivantinib serum concentrations were not dose-proportional. The most common (≥20%) adverse events (AEs) regardless of causality included rash (n = 17), fatigue (n = 12), nausea (n = 10), abdominal pain (n = 10), diarrhea (n = 9), bradycardia (n = 9), and anemia (n = 7). AEs considered related to study treatment occurred in 28 patients (87.5%), and 5 patients (15.6%) had treatment-related serious AEs, including neutropenia, leukopenia, syncope, sinus bradycardia, and sick sinus syndrome. Fifteen of 32 patients (46.8%) had a partial response (n = 1) or stable disease (n = 14) as assessed by Response Evaluation Criteria in Solid Tumors. Six of 8 patients with nonsmall cell lung cancer achieved stable disease. The recommended phase 2 dose is tivantinib 360 mg BID plus erlotinib 150 mg QD. CONCLUSIONS: Tivantinib plus erlotinib was well tolerated with encouraging clinical activity, especially in patients with nonsmall cell lung cancer. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The current study characterizes the overall survival (OS) and cause-specific survival (CSS) of patients with stage I nonsmall cell lung cancer (NSCLC) who were treated with radiotherapy alone, and analyzes the variables potentially affecting survival outcomes. METHODS: A total of 8524 patients with stage I NSCLC (according to the sixth edition of the American Joint Committee on Cancer staging manual) who were diagnosed between 1988 and 2008 were retrospectively analyzed using the population-based Surveillance, Epidemiology, and End Results database. Cox regression analysis was used to calculate hazard ratios (HR) from multivariate analyses. RESULTS: The 1-year, 2-year, and 5-year OS rates were 62%, 37%, and 11%, respectively; the corresponding lung cancer CSS survival rates were 68%, 45%, and 20%, respectively. Approximately 77% of deaths were from lung cancer (5292 of 6891 total deaths). Cardiac (n = 477 deaths) and pulmonary (other than lung cancer deaths; n = 475 deaths) deaths accounted for 14% of deaths. From Cox proportional hazards analyses, male sex (HR, 1.2) and squamous cell carcinoma histology (HR, > 1.1) were found to be significantly ( P < .0001) adverse prognostic factors for both OS and lung cancer CSS. A more recent calendar year of diagnosis was associated with significantly ( P < .0001) improved OS (HR, 0.84 per decade) and lung cancer CSS. This trend was also significant ( P < 0.0001) when restricting analyses to those patients with tumors measuring ≤ 5 cm (n = 5402 patients). T1 classification (vs T2 or T unknown) and smaller tumor size were found to be significantly ( P < .0001) favorable factors. CONCLUSIONS: From a population-based registry analysis of patients with stage I NSCLC, significant (albeit modest) improvements in survival in more recent years were appreciated, which likely reflect technologic advances in the diagnosis of, staging of, and radiotherapy for NSCLC. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer. METHODS: Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m2 and carboplatin at an area under the concentration-time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression. RESULTS: In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment-related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow-up of 15.8 months, the median progression-free survival was 7.1 months (95% confidence interval, 5.9-8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8-25.5 months). CONCLUSIONS: Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this study was to document the differences in testosterone (T) levels between crizotinib-treated and noncrizotinib-treated patients with metastatic nonsmall cell lung cancer (NSCLC). METHODS: Testosterone levels were measured in 19 men with metastatic NSCLC who received crizotinib and in 19 men with metastatic NSCLC who did not receive crizotinib. Clinical characteristics of the patients were compared, and additional hormone assays were performed as appropriate. Two patients who began crizotinib and 4 patients who had dose interruptions or who stopped crizotinib therapy had serial hormone measurements, permitting the documentation of dynamic hormone changes on and off crizotinib treatment. RESULTS: Total T levels were low (<241 ng/dL) in 19 of 19 (100%) crizotinib-treated men and in 6 of 19 men (32%) with metastatic NSCLC who did not receive crizotinib (mean T levels, 131 ng/dL and 311 ng/dL, respectively; P = .0002). Only 1 in 5 patients who had anaplastic lymphoma kinase ( ALK) gene rearrangements and had not yet received crizotinib had low T. The initiation of crizotinib in 2 patients who had previously normal T levels was associated with a rapid decreases in T and in luteinizing hormone and follicle stimulating hormone levels within 14 to 21 days. Discontinuation of crizotinib led to increases back to normal T levels. CONCLUSIONS: Crizotinib therapy caused rapid suppression of T levels in men. The current results indicated that the site of action must include a central (hypothalamic or pituitary) effect, but additional direct testicular effects could not be excluded. Further work is required to assess the correlation between low T levels and crizotinib side effects as well as the exact molecular mechanism and site of drug toxicity. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies examining the impact of lower socioeconomic status (SES) on the outcomes of patients with nonsmall cell lung cancer (NSCLC) are inconsistent. The objective of this study was to clearly elucidate the association between SES, education, and clinical outcomes among patients with NSCLC. METHODS: The study population was derived from a consecutive, retrospective cohort of patients with NSCLC who received treatment within the Duke Health System between 1995 and 2007. SES determinants were based on the individual's census tract and corresponding 2000 Census data. Determinants included the percentage of the population living below poverty, the median household income, and the percentages of residents with at least a high school diploma and at least a bachelor's degree. The SES and educational variables were divided into quartiles. Statistical comparisons were performed using the 25th and 75th percentiles. RESULTS: Individuals who resided in areas with a low median household income or in which a high percentage of residents were living below the poverty line had a shorter cancer-specific 6-year survival than individuals who resided in converse areas ( P = .0167 and P = .0067, respectively). Those living in areas in which a higher percentage of residents achieved a high school diploma had improved disease outcomes compared with those living in areas in which a lower percentage attained a high school diploma ( P = .0033). A survival advantage also was observed for inhabitants of areas in which a higher percentage of residents attained a bachelor's degree ( P = .0455). CONCLUSIONS: Low SES was identified as an independent prognostic factor for poor survival in patients with both early and advanced stage NSCLC. Patients who lived in areas with high poverty levels, low median incomes, and low education levels had worse mortality. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis. METHODS: A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort ( EGFR, KRAS, or ALK) and the triple negative cohort. RESULTS: ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001). CONCLUSIONS: The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Matrix metalloproteinase-2 ( MMP-2) is well known for its critical role in cell survival and cancer development. It also plays an important role in hematopoietic recovery after chemotherapy-induced myelosuppression. In this study, the authors investigated the association of MMP-2 polymorphisms with treatment efficacy and the occurrence of severe toxicity in patients with nonsmall cell lung cancer (NSCLC) who were receiving first-line, platinum-based chemotherapy. METHODS: A pharmacogenetic association study was performed in 663 Chinese patients who had inoperable stage III/IV NSCLC and were receiving first-line, platinum-based regimens. Information about objective response, progression-free survival, overall survival, grade 3 or 4 gastrointestinal toxicity (nausea/vomiting), and hematologic toxicity (neutropenia, anemia, thrombocytopenia) was available. Sixteen tag single nucleotide polymorphisms (SNPs) of MMP-2 were assessed. RESULTS: In 7 polymorphisms, significant associations were observed with the incidence of grade 3 or 4 neutropenia. The variant homozygotes of reference SNP rs12934241 exhibited the most significant effect on the risk of neutropenia, leading to an incidence rate that increased from 12.3% (for the C/C genotype) to 50% (for the T/T genotype; odds ratio, 8.33; P = 8.8 × 10−5). Stratified analyses indicated that rs12934241 exhibited a much stronger influence in the cisplatin-gemcitabine regimen subgroup than subgroups that received other regimens ( Pinteraction = .003). Further haplotype analyses produced results that were consistent with results from single-SNP analyses. However, no significant association was observed between MMP-2 polymorphisms and treatment efficacy, including response rate, clinical benefit, progression-free survival, and overall survival. CONCLUSIONS: To the authors' knowledge, this study provides the first evidence for a predictive role of MMP-2 polymorphisms in the variability of severe chemotherapy-related neutropenia among Chinese patients with platinum-treated, advanced NSCLC. Cancer 2012;3587-3598. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The anaplastic lymphoma kinase (ALK) gene is involved frequently in chromosomal translocations, resulting in fusion genes with different partners found in various lymphoproliferative conditions. It was recently reported in nonsmall cell lung cancer (NSCLC) that the fusion protein encoded by echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene conferred oncogenic properties. The objective of the current study was to identify other possible ALK fusion genes in NSCLC. METHODS: Immunohistochemical analysis was used to screen for aberrant ALK expression in primary NSCLC. The authors used 50 rapid amplification of complementary DNA ends to screen for potential, novel 50 fusion partners of ALK other than EML4-ALK. Reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization analyses were used to confirm the identity of 50 fusion partners. The genomic breakpoint was verified using genomic sequencing. Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4-ALK was performed to assess downstream signaling and functional effects. RESULTS: The authors identified a novel gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 15 to ALK exon 20 in a primary lung adenocarcinoma. Western blot analysis of clinical tumor tissues revealed the expression of a protein whose size correlated with that of the predicted KIF5B-ALK. Overexpression of KIF5B-ALK in mammalian cells led to the activation of signal transducer and activator of transcription 3 and protein kinase B and to enhanced cell proliferation, migration, and invasion. CONCLUSIONS: The discovery of the novel KIF5B-ALK variant further consolidated the role of aberrant ALK signaling in lung carcinogenesis. [ABSTRACT FROM AUTHOR]

The article discusses a study on the racial differences in hospice service use among older patients with nonsmall cell lung cancer (NSCLC) based on geographic residence and socioeconomic status (SES). It notes that hospice care is recommended for patients with life-threatening disease who are expected to live for less than six months and in need of palliative care. Results show that African American, Asian/Pacific Islander and Hispanic Medicare patients are less likely to avail of hospice service as compared to their Caucasian counterparts.

BACKGROUND. The optimal treatment of the primary tumor in patients with brain metastases (BM) from newly diagnosed nonsmall cell lung cancer (NSCLC) remains unclear. The authors aimed to identify patient groups with synchronous BM for whom radical treatment of the primary site may be appropriate. METHODS. The medical records of 167 patients treated at our center between November 2000 and June 2009 for newly diagnosed NSCLC and synchronous BM were reviewed. All patients underwent surgery/radiosurgery (n = 86) or whole-brain radiotherapy (WBRT; n = 81) for BM. Univariate and multivariate analyses assessed prognostic factors significant for overall survival (OS). RESULTS. Median OS of patients undergoing surgery/radiosurgery for BM was 12.1 months. Those undergoing "radical" thoracic treatment (n = 24) had a longer median OS (28.4 months) than those undergoing chemotherapy (n = 74; 12.1 months) or supportive therapy (n = 69; 5.6 months, P < .01). Patients with stage I thoracic disease (n = 23) had a longer median OS (18.5 months) than those with stage III (n = 43; 9.4 months) or with intra/extra-thoracic metastases other than BM (stage IV; n = 20; 2.7 months, P < .01). Median OS of WBRT patients was 3.7 months. One patient underwent radical thoracic treatment. Patients undergoing chemotherapy (n = 42) had a longer median OS (5.7 months) than patients undergoing supportive therapy only (n = 38; 1.6 months, P < .01). Performance status and age were also associated with OS. CONCLUSIONS. Radical thoracic treatments may be justified in selected patients <65-years-old, eligible to undergo surgery/radiosurgery for synchronous BM from NSCLC, even when stage III thoracic disease is present. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circadian cell-cycle progression causes fluctuating radiosensitivity in many tissues, which could affect clinical outcomes. The purpose of this study was to determine whether outcomes of single-session gamma knife radio-surgery (GKRS) for metastatic nonsmall cell lung cancer (NSCLC) differ based on treatment time. METHODS: Fifty-eight patients received GKRS between 10:00 am and 12:30 pm and 39 patients received GKRS between 12:30 pm and 3:00 pm. The mean peripheral dose was 18.6 Gy. The mean tumor size was 7.3 cm³. Magnetic resonance imaging was used to score local control at 3 months. Cause of death (COD) was categorized as central nervous system (CNS)-related or systemic. RESULTS: Demographic and disease characteristics of the 2 groups were similar. Local control at 3 months was achieved in 97% (35/36) of patients who underwent GKRS early in the day versus 67% (8/12) of patients who underwent GKRS later in the day (chi-square, P = .014). Early GKRS was associated with better survival (median 9.5 months) than late GKRS (median 5 months) (Kaplan-Meier log-rank test, P = .025). Factors contributing to better survival in a Cox regression model included early treatment time (P = .004) and recursive partition analysis class (P < .001). Cause of death in the early treatment group was CNS-related in 6% (3/47) of patients versus 24% (8/34) of patients in the late treatment group (chi-square test, P = .026). CONCLUSIONS: GKRS for metastatic NSCLC had better local control, better survival, and a lower rate of CNS-related cause of death when given earlier in the day versus later in the day. These retrospective data should encourage future study in brain radiosurgery and non-CNS stereotactic body radiotherapy series. [ABSTRACT FROM AUTHOR]

The article presents information on a study which evaluated the relationship between amphiregulin (AR) expression and the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in patients with wild-type (WT) EGFR-positive nonsmall cell lung cancer (NSCLC). A review of the related literature is presented. Immunohistochemistry was utilized to determine AR expression. It discusses the findings of the study including treatment outcome and association between AR expression and clinical outcomes.

The article presents information on a study which determined which elements of resection reduce attainment of quality surgical resection (GQR) criteria and whether survival of patients with early stage nonsmall cell lung cancer (NSCLC) was affected by attainment of GQR. The level of attainment of GQR was based on the definition of the American College of Surgeons' Oncology Group, the National Comprehensive Cancer Network and OSI Pharmaceutical's RADIANT trial.

This article discusses a study which assessed the efficacy and toxicity of sorafenib as front-line therapy in patients with stage IIIB or IV nonsmall cell lung cancer (NSCLC). The patients were given sorafenib continuously and were evaluated every two weeks during the first eight weeks. Only one partial response (PR) was observed in the first 20 patients. Of the 25 patients, there were three PR and six cases with stable disease observed. The study concluded that sorafenib is not effective as front-line therapy in the general unselected NSCLC population.

This article presents a study which investigated the prognostic role of the angiogenesis-related Notch ligands and receptors and the prognostic impact of the coexpression of vascular endothelial growth factor-A and Notch signaling. The study involved tumor tissue samples from 335 patients with stage I and IIIA nonsmall cell lung cancer (NSCLC). The key findings and conclusions of the investigation are detailed.

The article offers information on a study which investigated the risk of developing brain metastases following definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC). A review of the related literature on brain metastases in NSCLC is offered. Data reviewed were records of all patients who underwent surgery for T1-T2 NO-N1 NSCLC at Duke University between 1995 and 2005. Kaplan-Meier method was employed to estimate the cumulative incidence of brain metastases and distant metastases. The findings of the study are presented in details.

The article offers information on a study which investigated the maximum tolerable dose of weekly gemcitabine given simultaneously with radiation and cisplatin in patients with locally advanced nonsmall cell lung cancer (NSCLC). A review of the related literature on gemcitabine treatment in NSCLC is offered. The dose-limiting toxicities according to Common Toxicity Criteria was also determined. Main outcome measure was maximum tolerated dose (MTD) of gemcitabine. The findings of the study are presented and discussed in detail.

The article presents information on a study which investigated association between interleukin (IL)-17 expression and human papillomavirus (HPV) infection in clinical nonsmall cell lung cancer (NSCLC) tissues and explored the effects of HPV infection on a human NSCLC cel line. A review of the related literature on IL-17 expression is offered. Immunohistochemistry was used to investigate IL-17 expression. A discussion on the findings of the study are presented. It concludes that HPV infection-induced IL-17 levels stimulate Mcl-1 expression.

The article explores the prognostic role of angiogenic markers in coexpression with immune system markers in patients with nonsmall cell lung cancer (NSCLC). Immunohistochemistry was used in order to examine the expression of vascular endothelial growth factor (VEGF) A (VEGF-A), VEGF receptor 2 (VEGFR-2) and lymphocytes. It showed that low tumor cell VEGF-A and VEGFR-2 expression combined with high lymphocyte infiltration have a strong and independent favorable prognostic impact in patients with NSCLC.

The article examines detection of epidermal growth factor receptor (EGFR) mutations by denaturing high-performance liquid chromatography (dHPLC) in patients with nonsmall cell lung cancer. It also analyzes the impact on response to therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKI). Patients included in the study were selected based on their known EGFR mutation status. Results of the study revealed that 40% of patients who received EGFR-TKI therapy during their treatment course had mutations of EGFR.

The article focuses on a study which analyzed the role of glycoprotein YKL-40 in nonsmall cell lung cancer (NSCLC). The study included 189 patients, diagnosed with stage IIIB and stage IV NSCLC, who received combined gemcitabine and vinorelbine or gemcitabine, vinorelbine and cisplatin. It found that high serum YKL-40 levels are associated with shorter survival.

The article discusses a study that assessed the possible prognostic value of cofilin (CFL1) as a biomarker for nonsmall cell lung cancer (NSCLC) patients. The three experimental approach includes the correlation of gene expression levels, an analysis of in vitro data from six different human NSCLC lines and the construction of a network-based model of CFL1 gene. The study suggested that CFL1 expression levels can be used for NSCLC management and therapy by identifying the patients who should receive more aggressive therapy to reverse a poor prognosis.

The article provides information on a study which determined the clinical outcomes between gefitinib-treated and erlotinib-treated patients with metastatic or recurrent nonsmall cell lung cancer (NSCLC). Study population were patients with metastatic or recurrent NSCLC who had progressed on poor therapies and given gefitinib or erlotinib therapy between January 2006 and December 2008. A discussion on the findings is offered. Researchers observed a similar antitumor benefits of gefitinib and erlotinib in terms of response rate and overall survival.

The article provides information on a study which assessed Bmil polycomb ring finger oncogene (Bmil) and enhancer of zeste homolog 2 (EZH2) protein expression in specimens of human nonsmall cell lung cancer (NSCLC). The study also investigated the association between Bmil and EZH2 proteins and several features, such as clinical and clinicopathologic parameters, cell biologic characteristics and patient outcomes. A detailed discussion the findings is presented.

The article presents a study on the clinical outcome of particle therapy for nonsmall cell lung cancer (NSCLC) stage 1. The study involved 80 stage 1 NSCLC patients who were treated with proton therapy or carbon-ion therapy from April 2003 to April 2007. Results showed the lack of significant differences in treatment outcomes and grade three pulmonary toxicity was detected in one patient. The study concluded that carbon-ion therapy and proton therapy are effective in NSCLC stage 1 treatment.

The article presents a study which analyzes the perception of U.S. nonpatient populations on lung cancer risk and determines whether race or sex factors influence the different views. It uses the data from the 2005 Health Information National Trends Survey (HINTS) to determine the views of American and African American patients about lung cancer mortality. Results show that answers to lung cancer-specific questions do not have differences by sex although there were some differences by race.

The article reports on the study which examined the aggressive multimodality treatments for nonsmall cell lung cancer (NSCLC) that could predict long-term survival. It notes that the five-year survival in patients with advanced NSCLC remained poor and limited to small pathological subsets. It indicates that patients with advanced stage lung cancer who did not belong to any of the subsets had lower chances of long-term survival.

The article presents a study which investigates the risk of central nervous system (CNS) failure among Korean patients with nonsmall-cell lung cancer (NSCLC) who benefited from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKls). The study examined 342 patients treated with gefitinib or erlotinib, and conducted biomarker and statistical analyses. It concludes that CNS failure is frequent among patients who responded positively to EGFR-TKI therapy.

The article presents a study that evaluates the connection of stage IIIB/IV nonsmall cell lung cancer (NSCLC) patient survival to pack-years of cigarette smoking. It states the smoking history and clinical data from stage IIIB/IV NSCLC patients were obtained through questionnaire method, and evaluated through univariate and multivariate analyses to determine the rate of overall survival. The study concludes that more pack-years was related with reduced survival among patients after diagnosis.

The article presents a study which evaluates the radiotherapy care for lung cancer patients in New South Wales (NSW). Data for diagnosis, staging, and treatment were obtained from clinicians through questionnaires for the analysis. Results show that patients with limited stage small cell lung cancer has the largest shortfall in the use radiotherapy for lung cancer patients in New South Wales. It also shows the suboptimal level of combined-modality treatment for potential curable lung cancer.

The article presents a study on the relationship between symptom severity ratings and survival outcomes of patients with advanced nonsmall cell lung cancer (NSCLC). Patients rated symptom severity before and after their first chemotherapy cycle and the prognostic values and changes in symptom severity were examined. The study showed an increased risk for shorter survival outcomes; thus, patients' symptom severity score should be regarded as it may provide useful information for their treatment.

The article presents a pilot study which investigated the therapeutic effect of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer. It notes that huachansu is a Chinese medicine for cancers which comes from dried toad venom from the skin glands of Bufo gargarizans or Bufo melanostictus. Results of the study revealed that no dose-limiting toxicities (DLTs) were observed in fifteen patients who participated in the trial.

The article presents a study which evaluates the actuarial risk of local failure (LF) after stage I to II nonsmall cell lung cancer (NSCLC) surgery. It assesses surgical and pathologic factors associated with LF in the entire cohort and a subgroup who underwent stage IB and II surgery using a multivariate Cox regression analysis. It emphasizes that local sites were involved in more than half of the disease recurrences after early stage NSCLC surgery.

The article presents a study which defines whether sex is associated with the outcome of patients treated with radiation for nonsmall cell lung cancer (NSCLC). Result shows that women are more likely to have earlier stage disease, however, they have better overall survival. It mentions several contributing factor to survival rate, such as age, weight loss and stage of the disease, however, sex is determinant in NSCLC patients who are receiving radiation.

The article presents a study which examined the gene expression of chemokine receptors. The result indicates that substantial expression of the CXCR3/4/7, a chemokine receptor, was observed in nonsmall cell lung cancer (NSCLC) cell lines that were examined. It asserts that the higher expression of CXR7 is associated with Rec-Distant and poof DFS in cancer patients.

The article discusses the efficacy of gemcitabine-based doublets and single-agent therapy for treating patients with advanced nonsmall cell lung cancer (NSCLC). The authors claim that single-agent therapy is the preferred treatment for older patients, while various combinations of third-generation agents have yielded contradictory results. Meanwhile, G-based doublets is effective in treating elderly patients with advanced NSCLC who were not suitable for full-dose platinum-based chemotherapy.

The article presents a study investigating several histologic types of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) in Chinese patients with nonsmall lung cancer (NSCLC). The study used a sequential methods and immunohistochemistry in determination of EML4-ALK fusion gene and its protein expression. Results show the prevalence of various histologic types of NSCLC in EML4-ALK fusion gene.

The article presents a study which focuses on a model that predicts outcomes in nonsmall cell lung cancer (NSCLC) patients who underwent salvage treatment with gefitinib. Clinical data of patients who were administered with gefitinib were analyzed based on clinical parameters including age, sex and smoking. The study revealed that the prognostic model may help clinicians in considering gefitinib as salvage therapy in NSCLC patients.

The article presents a study which aims to investigate the expression pattern and the significance of centromere protein H (CENP-H) in nonsmall cell lung cancer (NSCLC) patients. Expression level of CENP-H in NSCLC tissues were measured by immunohistochemistry staining. The study found higher expression level of CENP-H in cancer cell lines than in normal cells and noncancerous lung tissues. Researchers conclude that CENP-H may by used as biomarker for lung cancer patients.