Thoracic Oncology Service

New York City, NY, United States

Thoracic Oncology Service

New York City, NY, United States
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Janjigian Y.Y.,Gastrointestinal Oncology Service | Zakowski M.F.,Sloan Kettering Cancer Center | Ladanyi M.,Sloan Kettering Cancer Center | Pao W.,Vanderbilt University | And 6 more authors.
Journal of Thoracic Oncology | Year: 2011

Background: Patients with stage IV lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown. Methods: Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI. Results: The cohort consists of 167 patients with completely resected stages I to III lung adenocarcinoma. Ninety-three patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, and 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery, and adjuvant platinum chemotherapy, the 2-year disease-free survival (DFS) was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio = 0.53; 95% confidence interval: 0.28-1.03; p = 0.06). The 2-year overall survival was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (hazard ratio: 0.62; 95% confidence interval: 0.26-1.51; p = 0.296). Conclusions: Compared with patients who did not receive adjuvant TKI, we observed a trend toward improvement in DFS among individuals with resected stages I to III lung adenocarcinomas harboring mutations in EGFR exon 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit. Copyright © 2011 The International Association for the Study of Lung Cancer.

Grommes C.,Brain Tumor Center | Oxnard G.R.,Neuro radiology Service | Kris M.G.,Thoracic Oncology Service | Miller V.A.,Thoracic Oncology Service | And 5 more authors.
Neuro-Oncology | Year: 2011

Erlotinib is effective for epidermal growth factor receptor (EGFR) mutant lung cancer, but CNS penetration at standard daily dosing is limited. We previously reported that intermittent "pulsatile" administration of high-dose (1500 mg) erlotinib once weekly was tolerable and achieved concentrations in cerebrospinal fluid exceeding the half maximal inhibitory concentration for EGFR mutant lung cancer cells in a patient with leptomeningeal metastases; we now expand this paradigm to a series of 9 patients. We retrospectively identified patients with EGFR mutant lung cancer treated with pulsatile erlotinib for CNS metastases (brain and/or leptomeningeal) that occurred despite conventional daily erlotinib or other EGFR tyrosine kinase inhibitors. Mutations in available lung and CNS tissue were correlated with efficacy. Erlotinib was administered as monotherapy at a median dose of 1500 mg weekly. Best CNS radiographic response was partial in 67% (6/9, including 2 with isolated leptomeningeal metastases), stable disease in 11% (1/9), and progressive disease in 22% (2/9). Median time to CNS progression was 2.7 months (range, 0.8- 14.5 months) and median overall survival was 12 months (range, 2.5 months-not reached). Treatment was well tolerated. No acquired resistance mutations in EGFR were identified in the CNS metastases of 4 patients, including 1 harboring T790M outside the CNS. Pulsatile erlotinib can control CNS metastases from EGFR mutant lung cancer after failure of standard daily dosing.CNSdisease may not harbor acquired resistance mutations that develop systemically. A prospective trial is planned. © The Author(s) 2011.

Kadota K.,Sloan Kettering Cancer Center | Kadota K.,Kagawa University | D'Angelo S.P.,Thoracic Oncology Service | Moreira A.L.,Sloan Kettering Cancer Center | And 7 more authors.
American Journal of Surgical Pathology | Year: 2014

Multiple reports indicate that epidermal growth factor receptor (EGFR) mutations are associated with lepidic-pattern lung adenocarcinoma and that KRAS mutations are associated with invasive mucinous adenocarcinoma. We sought to investigate the association between EGFR and KRAS mutations and specific morphologic characteristics, such as predominant histologic subtype and mucinous features. Clinical data for 864 patients with resected lung adenocarcinoma that underwent molecular testing for EGFR and KRAS mutations were collected. Histologic subtyping was performed according to the IASLC/ATS/ERS lung adenocarcinoma classification, with attention given to signet-ring cell feature and extracellular mucin. EGFR mutations were detected using a polymerase chain reaction-based sizing assay, KRAS mutations were detected using Sanger sequencing, and ALK expression was detected using immunohistochemistry. Invasive mucinous adenocarcinoma was associated with KRAS mutation (P<0.001). Among invasive mucinous adenocarcinomas with KRAS mutation, a pure mucinous pattern was more common than a mixed mucinous/nonmucinous pattern (P=0.002). Invasive mucinous adenocarcinoma was associated with KRAS transition mutations (G→A) but not transversion mutations (G→T or G→C) compared with nonmucinous tumors (P=0.009). The lepidic-predominant group was associated with EGFR mutation compared with nonlepidic-predominant tumors (P=0.011). Extracellular mucin was associated with KRAS mutation (P<0.001), whereas signet-ring cell feature was not associated with EGFR or KRAS mutation (P=0.517). ALK expression was associated with signet-ring cell feature (P=0.001) but not with extracellular mucin (P=0.089). Our study shows that histologic patterns of mucin in lung adenocarcinoma - including invasive mucinous adenocarcinoma and extracellular mucin - are associated with KRAS mutation. © 2014 by Lippincott Williams & Wilkins.

Yu H.A.,Thoracic Oncology Service | Huang J.,Thoracic Service | Rimner A.,Sloan Kettering Cancer Center | Paik P.,Thoracic Oncology Service | And 7 more authors.
Journal of Thoracic Oncology | Year: 2013

BACKGROUND: Development of acquired resistance limits the utility of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for the treatment of EGFR-mutant lung cancers. There are no accepted targeted therapies for use after acquired resistance develops. Metastasectomy is used in other cancers to manage oligometastatic disease. We hypothesized that local therapy is associated with improved outcomes in patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI. METHODS: Patients who received non-central nervous system local therapy were identified by a review of data from a prospective biopsy protocol for patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy and other institutional biospecimen registry protocols. RESULTS: Eighteen patients were identified, who received elective local therapy (surgical resection, radiofrequency ablation, or radiation). Local therapy was well tolerated, with 85% of patients restarting TKI therapy within 1 month of local therapy. The median time to progression after local therapy was 10 months (95% confidence interval [CI]: 2-27 months). The median time until a subsequent change in systemic therapy was 22 months (95% CI: 6-30 months). The median overall survival from local therapy was 41 months (95% CI: 26-not reached). CONCLUSIONS: EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy are amenable to local therapy to treat oligometastatic disease when used in conjunction with continued EGFR inhibition. Local therapy followed by continued treatment with an EGFR TKI is well tolerated and associated with long PFS and OS. Further study in selected individuals in the context of other systemic options is required. Copyright © 2013 by the International Association for the Study of Lung Cancer.

Kadota K.,Sloan Kettering Cancer Center | Kadota K.,Kagawa University | Yoshizawa A.,Shinshu University | Motoi N.,Cancer Institute Hospital of Japanese Foundation for Cancer Research | And 3 more authors.
American Journal of Surgical Pathology | Year: 2014

According to the IASLC/ATS/ERS classification, the lepidic predominant pattern consists of 3 subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and nonmucinous lepidic predominant invasive adenocarcinoma. We reviewed tumor slides from 1038 patients with stage I lung adenocarcinoma, recording the percentage of each histologic pattern and measuring the invasive tumor size. Tumors were classified according to the IASLC/ATS/ERS classification: 2 were AIS, 34 MIA, and 103 lepidic predominant invasive. Cumulative incidence of recurrence (CIR) was used to estimate the probability of recurrence. Patients with AIS and MIA experienced no recurrences. Patients with lepidic predominant invasive tumors had a lower risk for recurrence (5-y CIR, 8%) than nonlepidic predominant tumors (n=899; 19%; P=0.003). Patients with >50% lepidic pattern tumors experienced no recurrences (n=84), those with >10% to 50% lepidic pattern tumors had an intermediate risk for recurrence (n=344; 5-y CIR, 12%), and those with ≤10% lepidic pattern tumors had the highest risk (n=610; 22%; P<0.001). CIR was lower for patients with ≤2 cm tumors than for those with >2 to 3 cm tumors (for both total and invasive tumor size), with the difference more pronounced for invasive tumor size (5-y CIR, 13% vs. 21% [total size; P=0.022] and 12% vs. 27% [invasive size; P<0.001]). Most patients with lepidic predominant adenocarcinoma who experienced a recurrence had potential risk factors, including sublobar resection with close margins (≤0.5 cm; n=2), 20% to 30% micropapillary component (n=2), and lymphatic or vascular invasion (n=2). It therefore may be possible to identify lepidic predominant adenocarcinomas that carry a low or high risk for recurrence. © 2014 by Lippincott Williams & Wilkins.

Yu H.A.,Thoracic Oncology Service | Yu H.A.,New York Medical College | Arcila M.E.,Sloan Kettering Cancer Center | Hellmann M.D,Thoracic Oncology Service | And 5 more authors.
Annals of Oncology | Year: 2014

Background: EGFR T790M is the most common mutation associated with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Baseline EGFR T790M mutations in EGFR TKI-naïve patients have been reported, but the frequency and their association with response to EGFR TKIs remain unclear. Patients and methods: The frequency of baseline EGFR T790M as detected by routine molecular genotyping was determined by reviewing clinical results obtained at our institution from 2009 to 2013. We also collected outcome data for treatment with EGFR TKIs. Results: To define the incidence of EGFR T790M, we reviewed 2774 sequentially tested patients with lung cancer who underwent molecular testing using a mass spectrometry-based assay, and 11 (0.5%) had baseline EGFR T790M. Compiling results from several molecular techniques, we observed EGFR T790M in tumors from 20 patients who had not previously been treated with an EGFR TKI. In all cases, EGFR T790M occurred concurrently with another EGFR mutation, L858R (80%, 16/20), or exon 19 deletion (20%, 4/20). Two percent of all pre-treatment EGFR-mutant lung cancers harbored an EGFR T790M mutation. Thirteen patients received erlotinib monotherapy as treatment for metastatic disease. The response rate was 8% (1/13, 95% confidence interval 0%-35%). For the patients who received erlotinib, the median progression-free survival was 2 months and the median overall survival was 16 months. Conclusions: De novo EGFR T790M mutations are rare (<1%) when identified by standard sensitivity methods. TKI therapy for patients with baseline EGFR T790M detected by standard molecular analysis has limited benefit. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Takezawa K.,Vanderbilt Ingram Cancer Center | Pirazzoli V.,Yale University | Arcila M.E.,Thoracic Oncology Service | Nebhan C.A.,Vanderbilt Ingram Cancer Center | And 12 more authors.
Cancer Discovery | Year: 2012

EGF receptor (EGFR)-mutant lung cancers eventually become resistant to treatment with EGFR tyrosine kinase inhibitors (TKI). The combination of EGFR-TKI afatinib and anti-EGFR antibody cetuximab can overcome acquired resistance in mouse models and human patients. Because afatinib is also a potent HER2 inhibitor, we investigated the role of HER2 in EGFR -mutant tumor cells. We show in vitro and in vivo that afatinib plus cetuximab signifi cantly inhibits HER2 phosphorylation. HER2 overexpression or knockdown confers resistance or sensitivity, respectively, in all studied cell line models. FISH analysis revealed that HER2 was amplifi ed in 12% of tumors with acquired resistance versus only 1% of untreated lung adenocarcinomas. Notably, HER2 amplifi cation and EGFR T790M were mutually exclusive. Collectively, these results reveal a previously unrecognized mechanism of resistance to EGFR-TKIs and provide a rationale to assess the status and possibly target HER2 in EGFR -mutant tumors with acquired resistance to EGFR-TKIs. SIGNIFICANCE: Because all EGFR -mutant lung adenocarcinomas eventually develop resistance to TKI therapy, understanding mechanisms of acquired resistance may improve clinical outcomes. These results implicate HER2 as a novel protein involved in the sensitivity or resistance of EGFR -mutant lung cancer and provide a rationale to assess the status of and possibly target HER2 in such tumors. ©2012 AACR.

Arcila M.E.,Sloan Kettering Cancer Center | Nafa K.,Sloan Kettering Cancer Center | Chaft J.E.,Thoracic Oncology Service | Rekhtman N.,Sloan Kettering Cancer Center | And 5 more authors.
Molecular Cancer Therapeutics | Year: 2013

In contrast to other primary epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas, insertions in exon 20 of EGFR have been generally associated with resistance to EGFR-tyrosine kinase inhibitors. Their molecular spectrum, clinicopathologic characteristics, and prevalence are not well established. Tumors harboring EGFR exon 20 insertions were identified through an algorithmic screen of 1,500 lung adenocarcinomas. Cases were first tested for common mutations in EGFR (exons 19 and 21) and KRAS (exon 2) and, if negative, further analyzed for EGFR exon 20 insertions. All samples underwent extended genotyping for other driver mutations in EGFR, KRAS, BRAF, ERBB2/HER2, NRAS, PIK3CA, MEK1, and AKT by mass spectrometry; a subset was evaluated for ALK rearrangements. We identified 33 EGFR exon 20 insertion cases [2.2%, 95% confidence interval (CI), 1.6-3.1], all mutually exclusive with mutations in the other genes tested (except PIK3CA). They were more common among never-smokers (P < 0.0001). There was no association with age, sex, race, or stage. Morphologically, tumors were similar to those with common EGFR mutations but with frequent solid histology. Insertions were highly variable in position and size, ranging from 3 to 12 bp, resulting in 13 different insertions, which, by molecular modeling, are predicted to have potentially different effects on erlotinib binding. EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases, representing the third most common type of EGFR mutation after exon 19 deletions and L858R. Insertions are structurally heterogeneous with potential implications for response to EGFR inhibitors. © 2012 American Association for Cancer Research.

D'Angelo S.P.,Thoracic Oncology Service | Janjigian Y.Y.,Thoracic Oncology Service | Ahye N.,Thoracic Oncology Service | Riely G.J.,Thoracic Oncology Service | And 10 more authors.
Journal of Thoracic Oncology | Year: 2012

BACKGROUND:: EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in patients with stage IV lung cancers. The clinical significance of these mutations in patients with resected stage I-III lung cancers is unclear. METHODS:: At our institution, resection specimens from patients with stage I-III lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during routine pathology analysis such that the results are available before consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8 years, overall survival was analyzed using multivariate analysis to control for potential confounders, including age, sex, stage, and smoking history. The impact of adjuvant erlotinib or gefitinib was examined in an independent data set of patients exclusively with EGFR mutation, in which date of recurrence was recorded. RESULTS:: In the overall population, we identified 227 KRAS (25%) and 222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk of death compared with those without EGFR mutations, overall survival (OS) HR 0.51 (95% confidence interval [CI]: 0.34-0.76, p < 0.001). Patients with KRAS-mutant lung cancers had similar outcomes compared with individuals with KRAS wild-type tumors, OS HR 1.17 (95% CI: 0.87-1.57, p = 0.30). A separate data set includes only patients with EGFR-mutant lung cancers identified over 10 years (n = 286). In patients with resected lung cancers and EGFR mutation, treatment with adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or death, disease-free survival HR 0.43 (95% CI: 0.26-0.72, p = 0.001), and a trend toward improved OS. CONCLUSIONS:: Patients with resected stage I-III lung cancers and EGFR mutation have a lower risk of death compared with patients without EGFR mutation. This may be because of treatment with EGFR TKIs. Patients with, and without KRAS mutation have similar OS. These data support reflex testing of resected lung adenocarcinomas for EGFR mutation to provide prognostic information and identify patients for enrollment on prospective clinical trials of adjuvant EGFR TKIs. © 2012 by the International Association for the Study of Lung Cancer.

News Article | November 29, 2016

Interview with Dr. Marjorie Zauderer, MD, of Memorial Sloan Kettering Cancer Center, discussing mesothelioma treatments is now available on demand ALEXANDRIA, VA--(Marketwired - November 29, 2016) - On Tuesday, November 1, the Meso Foundation held a Meet the Mesothelioma Experts session with Marjorie Zauderer, MD, of Memorial Sloan Kettering Cancer Center (MSKCC). During the call, Dr. Zauderer discussed her work as a medical oncologist at MSKCC in an interview with Mary Hesdorffer, the Meso Foundation's executive director and expert nurse practitioner. Dr. Zauderer specializes in the care of patients with lung cancer and mesothelioma. Her practice aims to provide personalized care to patients throughout the course of their treatment. She also conducts clinical trials focused on novel therapies for the treatment of mesothelioma and lung cancer. Several trials with novel agents and new approaches are ongoing in MSKCC's multidisciplinary Mesothelioma Program and Thoracic Oncology Service. The interview is available at Mesothelioma is a malignant tumor of the lining of the lung, abdomen, or heart known to be caused by exposure to asbestos. With the life expectancy of less than one year after diagnosis, medical experts consider it one of the most aggressive and deadly of all cancers. An estimated one-third of those who develop mesothelioma were exposed while serving in the Navy or working in shipyards. Currently, few treatment options exist. There is no cure. ABOUT THE MESOTHELIOMA APPLIED RESEARCH FOUNDATION The Meso Foundation is the only 501(c)(3) nonprofit organization dedicated to eradicating mesothelioma and easing the suffering caused by this cancer. The Meso Foundation actively seeks philanthropic support to fund mesothelioma research; provide patient support services and education; and advocate Congress for increased federal funding for mesothelioma research. The Meso Foundation is the only non-government funder of peer-reviewed scientific research to develop life-saving treatments for this extremely aggressive cancer. To date, the Foundation has awarded over $9.4 million to research. More information is available at

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