Jyoti D Patel

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

Are you Jyoti D Patel?

Claim your profile

Publications (53)374.68 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: AUY922 is an HSP90 inhibitor that causes degradation of HSP chaperones and their client proteins, including epidermal growth factor receptor. We conducted a phase I/II trial to evaluate AUY922 and erlotinib for patients with EGFR-mutant lung cancer and disease progression during erlotinib treatment. All patients had developed acquired resistance after treatment with erlotinib and underwent repeat tumor biopsies before study entry to assess for EGFR T790M. In phase I, 18 patients were treated with AUY922 intravenously once per week and erlotinib once per day in 28-day cycles using a 3 + 3 dose-escalation design. In phase II, 19 additional patients were treated at the maximum-tolerated dose. The primary end point of the phase II trial was complete plus partial response rate. In phase I (n = 18), three patients were treated in each cohort, except the highest-dose cohort (AUY922 70 mg and erlotinib 150 mg), which expanded to six patients because of a dose-limiting toxicity (ie, junctional cardiac rhythm). Common drug-related adverse events were diarrhea, skin rash, hyperglycemia, and night blindness. All patients treated at maximum-tolerated dose (n = 25) were evaluable for response. The partial response rate was 16% (four of 25 patients; 95% CI, 5% to 36%) and was independent of tumor T790M status. Partial responses were observed, but the duration of treatment with AUY922 and erlotinib was limited by toxicities, especially night blindness. This phase II study of AUY922 and erlotinib did not meet its primary end point. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 04/2015; 33(15). DOI:10.1200/JCO.2014.59.7328 · 18.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Systemic Sclerosis (SSc) is a rare connective tissue disorder associated with an increased risk of malignancy including lung cancer. A single center review of all cases of lung cancer in patients with SSc was conducted. Clinical, radiographic, and detailed pathologic data was collected. Risk factors were compared with our center's SSc Registry. Cancer characteristics were compared with the National Cancer Institute SEER Cancer Statistics (NCI SEER) data. 17 cases were identified; the majority were females (82%) with the lung cancers diagnosed after the onset of SSc (88%). Tobacco use was identified in 65% of cases. Serologic testing showed 50% of cases were Scl-70 positive. Twelve cases had radiographic evidence of SSc lung involvement, however only 6 had restrictive physiology on pulmonary function testing. Thirteen cases had pulmonary nodules preceding lung cancer. Thirteen of the cancers were adenocarcinoma. Ten underwent molecular mutational profiling: 2/8 had KRAS mutation and 1/10 had EGFR mutation. More of the non-small cell lung cancers were diagnosed at localized disease (56%) than in the NCI SEER database. However, 5 years survival among the stage I cases was 25% versus an expected survival of 54%. The high proportion of adenocarcinomas seen in our study is different from that reported in the literature. Lung cancers were diagnosed at an early stage, likely due to our center's practice of radiographic screening for SSc associated lung involvement, however this did not confer a survival advantage. A high proportion of patients who developed lung cancer had interstitial lung disease.
    PLoS ONE 02/2015; 10(2):e0117829. DOI:10.1371/journal.pone.0117829 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Treatment impact on quality of life (QoL) informs treatment management decisions in advanced nonsquamous non-small-cell lung cancer (NS NSCLC). QoL outcomes from the phase III PointBreak trial are reported. Chemonaive patients (n = 939) with stage IIIB/IV nonsquamous non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status 0 to 1 were randomized (1:1) to pemetrexed-carboplatin-bevacizumab (pemetrexed arm) or paclitaxel-carboplatin-bevacizumab (paclitaxel arm). Patients without progressive disease received maintenance pemetrexed-bevacizumab (pemetrexed arm) or bevacizumab (paclitaxel arm). QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-General (FACT-G), FACT-Lung (FACT-L), and FACT/Gynecologic Oncology Group-Neurotoxicity (FACT-Ntx) instruments. Subscale scores, total scores, and trial outcome indices were analyzed using linear mixed-effects models. Post hoc analyses examined the association between baseline FACT scores and overall survival (OS). Mean score differences in change from baseline significantly favored the pemetrexed arm for the neurotoxicity subscale score, FACT-Ntx total scores, and FACT-Ntx trial outcome index. They occurred at cycle 2 (p < 0.001) and persisted through induction cycles 2 to 4 and six maintenance cycles. Investigator-assessed, qualitative, drug-related differences in grade 2 (1.6% versus 10.6%) and grade 3 (0.0% versus 4.1%) sensory neuropathy and grade 3/4 fatigue (10.9% versus 5.0%, p = 0.0012) were observed between the pemetrexed and paclitaxel arms. Baseline FACT-G, FACT-L, and FACT-Ntx scores were significant prognostic factors for OS (p < 0.001). Randomized patients reported similar changes in QoL, except for less change from baseline in neurotoxicity on the pemetrexed arm; investigators reported greater neurotoxicity on the paclitaxel arm and greater fatigue on the pemetrexed arm. Higher baseline FACT scores were favorable prognostic factors for OS.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2015; 10(2):353-9. DOI:10.1097/JTO.0000000000000277 · 5.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patient-level data from 2 phase III studies in patients with previously untreated, advanced-stage, nonsquamous non-small cell lung cancer (NSCLC) were pooled to examine outcomes with bevacizumab and chemotherapy based on age. Data from patients randomized to paclitaxel-carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 (E4599) and PointBreak studies were pooled and compared with E4599 patients randomized to PC alone. Patients were grouped by age: below 65, 65 to 74, 70 to 74, below 75, and 75 years or above. A multivariable model was used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using time-to-event outcomes. Adverse events (AEs) were assessed by age group in each study. The PC+bevacizumab and PC arms comprised 901 and 444 patients, respectively. PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.89), 65 to 74 years (HR, 0.80; 95% CI, 0.64-1.00), 70 to 74 years (HR, 0.68; 95% CI, 0.48-0.96), and below 75 years (HR, 0.78; 95% CI, 0.68-0.89) but not in those aged 75 years or above (HR, 1.05; 95% CI, 0.70-1.57). Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years (63% vs. 48%; P<0.05) and 75 years or above (81% vs. 56%; P <0.05) in E4599. This analysis suggests that the survival benefits associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC; no benefit, however, was observed for bevacizumab-eligible patients who were 75 years or above.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
    American Journal of Clinical Oncology 01/2015; DOI:10.1097/COC.0000000000000163 · 2.61 Impact Factor
  • Journal of Clinical Oncology 01/2015; 33(7). DOI:10.1200/JCO.2014.59.9746 · 18.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: African Americans (AA) have a higher incidence of lung cancer than Caucasians, and are underrepresented in clinical trials. In PointBreak (pemetrexed-carboplatin-bevacizumab and maintenance pemetrexed-bevacizumab [PemCBev] versus paclitaxel-carboplatin-bevacizumab and maintenance bevacizumab [PacCBev]), 10% of patients were AA. PointBreak was a negative study; PemCBev did not demonstrate superior overall survival (OS).Materials and Methods PointBreak subgroup efficacy and safety data were retrospectively analyzed: 1) AAs versus Caucasians for PemCBev; 2) PemCBev versus PacCBev in AAs; 3) academic versus community settings in AAs. Hazard ratios (HR) and p-values were derived from multivariate Cox proportional hazards model after adjusting for covariates.ResultsOf 939 intentto-treat (ITT) patients, 94 were AA and 805 were Caucasian. AA enrollment was uniform across study sites (median 1 AA per site). In the PemCBev arm, OS (HR=1.125; p=0.525), progression-free survival (PFS) (HR=1.229; p=0.251), response (p=0.607), and toxicity profiles were similar in AAs versus Caucasians. For AAs, OS (HR=1.375; p=0.209), PFS (HR=0.902; p=0.670), response (p=1.000), and toxicity profiles were similar in the PemCBev versus PacCBev arm. In AAs, there were no significant differences in OS (HR=0.661; p=0.191)/PFS (HR=0.969; p=0.915) in academic versus community practice settings.Conclusions In the PemCBev arm, this exploratory analysis showed no significant differences between AAs and Caucasians for efficacy outcomes or toxicity profiles. Consistent with the ITT population negative trial result, in AAs median OS was not superior for either arm. In AAs, PFS and OS were similar for academic and community settings. Additional outcomes data for AAs should be collected in lung cancer studies.
    Clinical Lung Cancer 11/2014; 16(3). DOI:10.1016/j.cllc.2014.11.004 · 3.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Molecular biomarkers, a cornerstone of precision oncology, are critical in breast, gastroesophageal, and non–small cell lung cancer management (BC, GEC, NSCLC). Testing practices are intensely debated, impacting diagnostic quality and affecting pathologists, oncologists and patients. However, little is known about testing approaches used in practice. Our study described biomarker practices in BC, GEC, and NSCLC at the leading US cancer centers.
    JNCI Journal of the National Cancer Institute 10/2014; 106(10). DOI:10.1093/jnci/dju256 · 15.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the last decade, new cytotoxic treatments and targeted therapies have altered treatment paradigms for patients with metastatic non-small cell lung cancer (NSCLC). We sought to analyze the impact of histology and biomarker selection criteria on outcomes of clinical trials in metastatic NSCLC reported over the last decade at the American Society of Clinical Oncology (ASCO) Annual Meeting. Data were collected from ASCO abstracts of Phase II–IV clinical trials for patients with metastatic NSCLC from 2004–2014. 770 of 2,989 identified metastatic NSCLC category abstracts met selection criteria. Despite a decline in the number of abstracts from 107 to 46 abstracts annually over this period, the proportion of trials with positive progression free survival (PFS) and overall survival (OS) outcomes has increased significantly. Trials with histology selection (6%) or molecular biomarker (15%) criteria were more likely to result in an improvement in PFS than those without selection criteria (21% vs. 8%, p = 0.0001 and 31% vs. 10%, p < 0.0001, respectively). These data demonstrate profound changes in the clinical trial landscape over the last 10 years with significantly increasing proportion of trials with positive outcomes. These changes are likely attributed to the use of histology and biomarker selection criteria in clinical trial design.
    Cancer 08/2014; 120(24). DOI:10.1002/cncr.28956 · 4.90 Impact Factor
  • Source
    Jama Ophthalmology 07/2014; 132(7):899-901. DOI:10.1001/jamaophthalmol.2014.409 · 3.83 Impact Factor
  • Ryan D Gentzler · Jyoti D Patel
    [Show abstract] [Hide abstract]
    ABSTRACT: During the past 10 years, the treatment of advanced-stage non-small cell lung cancer (NSCLC) has become increasingly complex, and debate continues regarding the optimal chemotherapeutic agents and duration of treatment. The addition of bevacizumab to platinum doublet chemotherapy, the use of pemetrexed for nonsquamous histology, and the introduction of maintenance chemotherapy are strategies that have been shown to improve overall survival beyond 12 months. Many acceptable treatment options are recommended in the NCCN Clinical Practice Guidelines in Oncology for NSCLC. This article discusses the first-line treatment of NSCLC with no identifiable mutations with FDA-approved targeted therapies for patients treated outside a clinical trial, particularly focusing on difficult clinical decisions, such as when the use of bevacizumab is appropriate, choosing a platinum partner, and treatment of patients with an ECOG performance status of 2. Data are summarized from several recent maintenance clinical trials, such as PARAMOUNT, AVAPERL, and PointBreak, and the implications these trials have on practical decisions oncologists must make when choosing an optimal treatment strategy for patients with advanced NSCLC are discussed.
    Journal of the National Comprehensive Cancer Network: JNCCN 06/2014; 12(6):889-97. · 4.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context .- Epidermal growth factor receptor (EGFR) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Objective .- To investigate the relationship of EGFR mutation status to the histologic subtype of adenocarcinoma according to the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. Design .- We screened EGFR mutation in 200 consecutive lung adenocarcinoma resection specimens diagnosed between 2008 and 2011. Results .- Among 200 lung adenocarcinomas, EGFR mutations were identified in 41 tumors (20.5%). The mean age in the EGFR-mutant group was 64.8 years and this group consisted of 78% females and 22% males. Most patients with EGFR-positive lung cancers were never-smokers (51%) as compared to 8% with EGFR-negative cancers (P < .001). The most common mutations identified in our population were deletions in exon 19 (22 patients) and L858R in exon 21 (12 patients). Five patients had double mutations. The predominant pattern of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers as compared to 69% with acinar pattern in EGFR wild-type lung cancers (P < .001). Of 22 minimally invasive adenocarcinomas, 8 (36%) had EGFR mutations, accounting for 20% of adenocarcinomas with EGFR mutation (P < .05). Conclusion .- Based on the new IASLC/ATS/ERS classification, the predominant subtype of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers (P < .001). However, histologic subtype should not be used to exclude patients from tyrosine kinase inhibitor therapy, since EGFR mutations are found in lung adenocarcinomas of other subtypes.
    Archives of pathology & laboratory medicine 02/2014; 138(10). DOI:10.5858/arpa.2013-0376-OA · 2.88 Impact Factor
  • Melissa L Johnson · Jyoti D Patel
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related death in the United States. Survival for patients with advanced disease remains meager with standard platinum-based doublet therapy even given initially. Improved efficacy and tolerability of third-generation chemotherapies and small-molecule inhibitors has prompted the evaluation of these agents in the maintenance setting in order to enhance current outcomes. Two separate strategies have evolved: the introduction of a non-cross-resistant drug immediately following first-line or induction chemotherapy (switch maintenance), or the continuation of the non-platinum partner initially introduced during induction (continuation maintenance). Here we review the available clinical trial data evaluating both maintenance strategies, and offer our assessment of their contemporary clinical implications and cost-effectiveness.
    Seminars in Oncology 02/2014; 41(1):93-100. DOI:10.1053/j.seminoncol.2013.12.007 · 3.94 Impact Factor
  • Ryan D Gentzler · Jyoti D Patel
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world. Despite significant progress in early stage disease, survival rates for advanced disease remain low. Maintenance therapy is a treatment strategy that has been investigated extensively in NSCLC. Therapies that have been studied in this setting in randomized trials to date include chemotherapy and molecularly targeted agents. Following the development of multiple new agents that show activity in NSCLC and have a tolerable side-effect profile, there has been increasing interest in utilizing them to maintain response to initial therapy after treatment with platinum-based doublets. Two effective strategies have evolved: continuation and switch maintenance. Despite improvements in progression-free survival and often overall survival on multiple clinical trials, there remains considerable controversy around this treatment paradigm. Here, we briefly outline the evolution of this treatment strategy and examine the available data, including recently updated data from the PARAMOUNT, AVAPERL, and PointBreak maintenance trials. Ultimately, the decision to use maintenance chemotherapy requires a nuanced discussion between the patient and physician that adequately assesses benefits of prolonged therapy and impact in terms of toxicity, quality of life, and financial cost.
    01/2014; 6(1):4-15. DOI:10.1177/1758834013510589
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Since its founding in 1964, the American Society of Clinical Oncology (ASCO) has been committed to improving cancer outcomes through research and the delivery of quality care. Research is the bedrock of discovering better treatments-providing hope to the millions of individuals who face a cancer diagnosis each year.The studies featured in "Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" represent the invaluable contributions of thousands of patients who participate in clinical trials and the scientists who conduct basic and clinical research. The insights described in this report, such as how cancers hide from the immune system and why cancers may become resistant to targeted drugs, enable us to envision a future in which cancer will be even more controllable and preventable.The scientific process is thoughtful, deliberate, and sometimes slow, but each advance, while helping patients, now also points toward new research questions and unexplored opportunities. Both dramatic and subtle breakthroughs occur so that progress against cancer typically builds over many years. Success requires vision, persistence, and a long-term commitment to supporting cancer research and training.Our nation's longstanding investment in federally funded cancer research has contributed significantly to a growing array of effective new treatments and a much deeper understanding of the drivers of cancer. But despite this progress, our position as a world leader in advancing medical knowledge and our ability to attract the most promising and talented investigators are now threatened by an acute problem: Federal funding for cancer research has steadily eroded over the past decade, and only 15% of the ever-shrinking budget is actually spent on clinical trials. This dismal reality threatens the pace of progress against cancer and undermines our ability to address the continuing needs of our patients.Despite this extremely challenging economic environment, we continue to make progress. Maintaining and accelerating that progress require that we keep our eyes on the future and pursue a path that builds on the stunning successes of the past. We must continue to show our policymakers the successes in cancer survival and quality of life (QOL) they have enabled, emphasizing the need to sustain our national investment in the remarkably productive US cancer research enterprise.We must also look to innovative methods for transforming how we care for-and learn from-patients with cancer. Consider, for example, that fewer than 5% of adult patients with cancer currently participate in clinical trials. What if we were able to draw lessons from the other 95%? This possibility led ASCO this year to launch CancerLinQ, a groundbreaking health information technology initiative that will provide physicians with access to vast quantities of clinical data about real-world patients and help achieve higher quality, higher value cancer care.As you read the following pages, I hope our collective progress against cancer over the past year inspires you. More importantly, I hope the pride you feel motivates you to help us accelerate the pace of scientific advancement.Clifford A. Hudis, MD, FACPPresidentAmerican Society of Clinical Oncology.
    Journal of Clinical Oncology 12/2013; 32(2). DOI:10.1200/JCO.2013.53.7076 · 18.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). Patients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were randomly assigned to receive pemetrexed 500 mg/m(2) or paclitaxel 200 mg/m(2) combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles. Eligible patients received maintenance until disease progression: pemetrexed plus bevacizumab (for the PemCBev group) or bevacizumab (for the PacCBev group). The primary end point of this superiority study was overall survival (OS). Patients were randomly assigned to PemCBev (n = 472) or PacCBev (n = 467). For PemCBev versus PacCBev, OS hazard ratio (HR) was 1.00 (median OS, 12.6 v 13.4 months; P = .949); progression-free survival (PFS) HR was 0.83 (median PFS, 6.0 v 5.6 months; P = .012); overall response rate was 34.1% versus 33.0%; and disease control rate was 65.9% versus 69.8%. Significantly more study drug-related grade 3 or 4 anemia (14.5% v 2.7%), thrombocytopenia (23.3% v 5.6%), and fatigue (10.9% v 5.0%) occurred with PemCBev; significantly more grade 3 or 4 neutropenia (40.6% v 25.8%), febrile neutropenia (4.1% v 1.4%), sensory neuropathy (4.1% v 0%), and alopecia (grade 1 or 2; 36.8% v 6.6%) occurred with PacCBev. OS did not improve with the PemCBev regimen compared with the PacCBev regimen, although PFS was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability.
    Journal of Clinical Oncology 10/2013; 31(34). DOI:10.1200/JCO.2012.47.9626 · 18.43 Impact Factor
  • Ryan D Gentzler · Sarah E Yentz · Jyoti D Patel
    [Show abstract] [Hide abstract]
    ABSTRACT: Bevacizumab is an effective targeted therapy with demonstrated survival benefits for many patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Some patient populations are at higher risk for bleeding complications and bevacizumab should be avoided, but advanced age should not be used as the sole exclusion criterion for use. Bevacizumab is generally a well-tolerated therapy that can be safely given in combination with multiple chemotherapy agents in the induction and maintenance phases of therapy. The optimal maintenance strategy is yet to be determined and is the focus of ongoing trials, such as ECOG 5508. Early use of bevacizumab in the adjuvant setting and continued use in the second-line setting are being investigated in current clinical trials.
    Current Treatment Options in Oncology 08/2013; 14(4). DOI:10.1007/s11864-013-0255-3 · 3.24 Impact Factor
  • Source
    2013 ASCO Annual Meeting; 06/2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations. Copyright © 2015 by the National Comprehensive Cancer Network.
    Journal of the National Comprehensive Cancer Network: JNCCN 06/2013; 11(6):645-653. · 4.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.
    Journal of the National Comprehensive Cancer Network: JNCCN 05/2013; 11(5):562-76. · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context.-Lung carcinoma is the result of sequential accumulation of genetic and epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse somatic mutations, and several of them include the so-called driver mutations, which may serve as "druggable" therapeutic targets. Thus, development of personalized approaches for the treatment of non-small cell lung carcinoma (NSCLC) mandates that pathologists make a precise histologic classification inclusive of routine molecular analysis of such tumors. Objective.-To address the molecular mechanisms underlying NSCLC and how this knowledge reflects the multidisciplinary approach in the diagnosis and management of these patients. We will also summarize the current available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, and metastatic NSCLC. Data Sources.-Peer-reviewed published literature and personal experience. Conclusions.-There are multiple mechanisms involved in the pathogenesis of lung cancer, which operate in parallel and involve pathways of activation and inhibition of various cellular events. Further research is essential to characterize the histologic and mutational profiles of lung carcinomas, which will ultimately translate into improved and more personalized therapeutic management of patients with lung cancer.
    Archives of pathology & laboratory medicine 04/2013; 137(4):481-91. DOI:10.5858/arpa.2012-0287-RA · 2.88 Impact Factor

Publication Stats

1k Citations
374.68 Total Impact Points

Institutions

  • 2003–2015
    • Memorial Sloan-Kettering Cancer Center
      • Thoracic Oncology Service
      New York, New York, United States
  • 2004–2014
    • Northwestern University
      • • Division of Hematology/Oncology
      • • Division of Hospital Medicine
      Evanston, Illinois, United States
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States