Grant Number:	5R21CA164568-02 Interpret this number
Primary Investigator:	Adusumilli, Prasad
Organization:	Sloan-Kettering Inst Can Research
Project Title:	Validation of a Risk Model for Stage I Lung Adenocarcinoma
Fiscal Year:	2013

DESCRIPTION (provided by applicant): Development and validation of a prognostic model for predicting recurrence in stage I lung adenocarcinoma. With the recent disclosure of results from the National Lung Cancer Screening Trial, suggesting that annual chest CT scans can reduce 20% of lung cancer deaths in high-risk individuals, the number of early stage LACs detected by screening CT scans and their resection is expected to increase. While the 5-year recurrence rate following curative-intent surgical resection in stage I LAC is 18% - 29%, there is substantial individual variation in post-resection recurrence free survival. Currently, the only accepted prognostic factor guiding treatment decisions for both surgeons and oncologists is tumor size, and its prognostic performance remains unclear. Better prognostic tools are needed to provide good quality individual risk prediction, identify patients at high risk of recurrence and help to guide treatment decisions by both oncologists and thoracic surgeons. In an attempt to identify prognostic markers that accurately predict the risk of unfavorable outcome; our group has performed extensive clinical and pathological examination of the largest cohort of stage I LAC to date. We have developed a prediction score that uses combined clinical, histological and cytological criteria that can be assessed routinely on an H&E slide in any hospital, and predicts the risk of recurrence or death with high accuracy. In this proposal, we aim to further improve the predictive ability of our score by microRNA analysis (miRNA). The potential of using microRNAs for prognostication of early lung cancer has been established by several investigators independently including our group. We have developed a microRNA signature capable of prognostication of early lung cancer. A distinct advantage of our methods is the use of formalin-fixed paraffin-embedded (FFPE) tissue, similar to our clinico-pathologic criteria, thus avoiding the requirement of complex tissue processing protocols. We hypothesize that the comprehensive clinico-pathological score, enriched with miRNA expression data, can be combined into a simple, cost-effective predictive instrument that will accurately determine the risk of recurrence or death following curative-intent surgical resection for stage I LAC, and will identify those patients who are primary candidates for aggressive surveillance and adjuvant therapy. In this proposal, we seek to validate and refine our existing miRNA signature for LAC and examine its ability to enrich the predictive quality of our clinico-pathological score. As the model is built upon simple clinical, pathological characteristics (assessed on H&E slide) and miRNA analysis from FFPE, the results of our proposal are immediately implementable, timely and are of high translational significance.




Immunotherapy for malignant pleural mesothelioma: current status and future directions.
Authors: Dozier J. , Zheng H. , Adusumilli P.S. .
Source: Translational Lung Cancer Research, 2017 Jun; 6(3), p. 315-324.
PMID: 28713676
Related Citations

CAR T-cell therapy for lung cancer and malignant pleural mesothelioma.
Authors: Zeltsman M. , Dozier J. , McGee E. , Ngai D. , Adusumilli P.S. .
Source: Translational Research : The Journal Of Laboratory And Clinical Medicine, 2017-04-26 00:00:00.0; , .
EPub date: 2017-04-26 00:00:00.0.
PMID: 28502785
Related Citations

Kras Mutation Is A Significant Prognostic Factor In Early-stage Lung Adenocarcinoma
Authors: Kadota K. , Sima C.S. , Arcila M.E. , Hedvat C. , Kris M.G. , Jones D.R. , Adusumilli P.S. , Travis W.D. .
Source: The American Journal Of Surgical Pathology, 2016-10-12 00:00:00.0; , .
PMID: 27740967
Related Citations

Spread through alveolar spaces: An aerogenous invasion in pulmonary adenocarcinomas.
Authors: Adusumilli P.S. .
Source: The Journal Of Thoracic And Cardiovascular Surgery, 2016 Jul; 152(1), p. 73-4.
PMID: 27158135
Related Citations

Immunotherapy for non-small cell lung cancer: current concepts and clinical trials.
Authors: Mayor M. , Yang N. , Sterman D. , Jones D.R. , Adusumilli P.S. .
Source: European Journal Of Cardio-thoracic Surgery : Official Journal Of The European Association For Cardio-thoracic Surgery, 2016 May; 49(5), p. 1324-33.
PMID: 26516195
Related Citations

Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors.
Authors: Morello A. , Sadelain M. , Adusumilli P.S. .
Source: Cancer Discovery, 2016 Feb; 6(2), p. 133-46.
PMID: 26503962
Related Citations

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma.
Authors: Yeh Y.C. , Kadota K. , Nitadori J. , Sima C.S. , Rizk N.P. , Jones D.R. , Travis W.D. , Adusumilli P.S. .
Source: European Journal Of Cardio-thoracic Surgery : Official Journal Of The European Association For Cardio-thoracic Surgery, 2016 Jan; 49(1), p. e9-e15.
PMID: 26377636
Related Citations

Nuclear estrogen receptor-¿ expression is an independent predictor of recurrence in male patients with pT1aN0 lung adenocarcinomas, and correlates with regulatory T-cell infiltration.
Authors: Kadota K. , Eguchi T. , Villena-Vargas J. , Woo K.M. , Sima C.S. , Jones D.R. , Travis W.D. , Adusumilli P.S. .
Source: Oncotarget, 2015-09-29 00:00:00.0; 6(29), p. 27505-18.
PMID: 26318038
Related Citations

Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early, Extrathoracic, Multisite Recurrence and of Poor Postrecurrence Survival.
Authors: Ujiie H. , Kadota K. , Chaft J.E. , Buitrago D. , Sima C.S. , Lee M.C. , Huang J. , Travis W.D. , Rizk N.P. , Rudin C.M. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2015-09-10 00:00:00.0; 33(26), p. 2877-84.
EPub date: 2015-09-10 00:00:00.0.
PMID: 26261257
Related Citations

Tumoral CD10 expression correlates with aggressive histology and prognosis in patients with malignant pleural mesothelioma.
Authors: Kadota K. , Villena-Vargas J. , Nitadori J. , Sima C.S. , Jones D.R. , Travis W.D. , Adusumilli P.S. .
Source: Annals Of Surgical Oncology, 2015 Sep; 22(9), p. 3136-43.
PMID: 25608772
Related Citations

Tumor Budding Correlates With the Protumor Immune Microenvironment and Is an Independent Prognostic Factor for Recurrence of Stage I Lung Adenocarcinoma.
Authors: Kadota K. , Yeh Y.C. , Villena-Vargas J. , Cherkassky L. , Drill E.N. , Sima C.S. , Jones D.R. , Travis W.D. , Adusumilli P.S. .
Source: Chest, 2015 Sep; 148(3), p. 711-21.
PMID: 25836013
Related Citations

Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis.
Authors: Kadota K. , Nitadori J. , Rekhtman N. , Jones D.R. , Adusumilli P.S. , Travis W.D. .
Source: The American Journal Of Surgical Pathology, 2015 Sep; 39(9), p. 1170-80.
PMID: 25871623
Related Citations

Tumoral CD10 expression correlates with high-grade histology and increases risk of recurrence in patients with stage I lung adenocarcinoma.
Authors: Kadota K. , Buitrago D. , Lee M.C. , Villena-Vargas J. , Sima C.S. , Jones D.R. , Travis W.D. , Adusumilli P.S. .
Source: Lung Cancer (amsterdam, Netherlands), 2015 Sep; 89(3), p. 329-36.
PMID: 26141216
Related Citations

Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor.
Authors: Kadota K. , Nitadori J. , Ujiie H. , Buitrago D.H. , Woo K.M. , Sima C.S. , Travis W.D. , Jones D.R. , Adusumilli P.S. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2015 Sep; 10(9), p. 1301-10.
PMID: 26291010
Related Citations

Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ¿ 3 cm: accuracy and interobserver agreement.
Authors: Yeh Y.C. , Nitadori J. , Kadota K. , Yoshizawa A. , Rekhtman N. , Moreira A.L. , Sima C.S. , Rusch V.W. , Adusumilli P.S. , Travis W.D. .
Source: Histopathology, 2015 Jun; 66(7), p. 922-38.
PMID: 24889415
Related Citations

The tumoral and stromal immune microenvironment in malignant pleural mesothelioma: A comprehensive analysis reveals prognostic immune markers.
Authors: Ujiie H. , Kadota K. , Nitadori J.I. , Aerts J.G. , Woo K.M. , Sima C.S. , Travis W.D. , Jones D.R. , Krug L.M. , Adusumilli P.S. .
Source: Oncoimmunology, 2015 Jun; 4(6), p. e1009285.
PMID: 26155428
Related Citations

Tumor Spread through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences after Limited Resection for Small Stage I Lung Adenocarcinomas.
Authors: Kadota K. , Nitadori J. , Sima C.S. , Ujiie H. , Rizk N.P. , Jones D.R. , Adusumilli P.S. , Travis W.D. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2015 May; 10(5), p. 806-14.
PMID: 25629637
Related Citations

Small RNA sequencing for profiling microRNAs in long-term preserved formalin-fixed and paraffin-embedded non-small cell lung cancer tumor specimens.
Authors: Buitrago D.H. , Patnaik S.K. , Kadota K. , Kannisto E. , Jones D.R. , Adusumilli P.S. .
Source: Plos One, 2015; 10(3), p. e0121521.
PMID: 25812157
Related Citations

Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity.
Authors: Adusumilli P.S. , Cherkassky L. , Villena-Vargas J. , Colovos C. , Servais E. , Plotkin J. , Jones D.R. , Sadelain M. .
Source: Science Translational Medicine, 2014-11-05 00:00:00.0; 6(261), p. 261ra151.
PMID: 25378643
Related Citations

Translational immunotherapeutics: chemoimmunotherapy for malignant pleural mesothelioma.
Authors: Adusumilli P.S. .
Source: Cancer, 2014-11-01 00:00:00.0; 120(21), p. 3268-71.
EPub date: 2014-11-01 00:00:00.0.
PMID: 24989696
Related Citations

Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence.
Authors: de Biasi A.R. , Villena-Vargas J. , Adusumilli P.S. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2014-11-01 00:00:00.0; 20(21), p. 5384-91.
EPub date: 2014-11-01 00:00:00.0.
PMID: 25204552
Related Citations

The tumor immune microenvironment in octogenarians with stage I non-small cell lung cancer.
Authors: Lee M.C. , Buitrago D.H. , Kadota K. , Ujiie H. , Woo K. , Sima C.S. , Travis W.D. , Jones D.R. , Adusumilli P.S. .
Source: Oncoimmunology, 2014 Nov; 3(11), p. e967142.
PMID: 25941595
Related Citations

Implementing the new IASLC/ATS/ERS classification of lung adenocarcinomas: results from international and Chinese cohorts.
Authors: Lee M.C. , Kadota K. , Buitrago D. , Jones D.R. , Adusumilli P.S. .
Source: Journal Of Thoracic Disease, 2014 Oct; 6(Suppl 5), p. S568-80.
PMID: 25349708
Related Citations

The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know.
Authors: Eguchi T. , Kadota K. , Park B.J. , Travis W.D. , Jones D.R. , Adusumilli P.S. .
Source: Seminars In Thoracic And Cardiovascular Surgery, 2014 Autumn; 26(3), p. 210-22.
PMID: 25527015
Related Citations

Comprehensive pathological analyses in lung squamous cell carcinoma: single cell invasion, nuclear diameter, and tumor budding are independent prognostic factors for worse outcomes.
Authors: Kadota K. , Nitadori J. , Woo K.M. , Sima C.S. , Finley D.J. , Rusch V.W. , Adusumilli P.S. , Travis W.D. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2014 Aug; 9(8), p. 1126-39.
PMID: 24942260
Related Citations

Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation.
Authors: Kadota K. , Yeh Y.C. , D'Angelo S.P. , Moreira A.L. , Kuk D. , Sima C.S. , Riely G.J. , Arcila M.E. , Kris M.G. , Rusch V.W. , et al. .
Source: The American Journal Of Surgical Pathology, 2014 Aug; 38(8), p. 1118-27.
PMID: 25029118
Related Citations

Recent advances and clinical implications of the micropapillary histological subtype in lung adenocarcinomas.
Authors: Lee M.C. , Buitrago D.H. , Kadota K. , Jones D.R. , Adusumilli P.S. .
Source: Lung Cancer Management, 2014-06-01 00:00:00.0; 3(3), p. 245-253.
PMID: 25202339
Related Citations

The cribriform pattern identifies a subset of acinar predominant tumors with poor prognosis in patients with stage I lung adenocarcinoma: a conceptual proposal to classify cribriform predominant tumors as a distinct histologic subtype.
Authors: Kadota K. , Yeh Y.C. , Sima C.S. , Rusch V.W. , Moreira A.L. , Adusumilli P.S. , Travis W.D. .
Source: Modern Pathology : An Official Journal Of The United States And Canadian Academy Of Pathology, Inc, 2014 May; 27(5), p. 690-700.
PMID: 24186133
Related Citations

Prognostic significance of adenocarcinoma in situ, minimally invasive adenocarcinoma, and nonmucinous lepidic predominant invasive adenocarcinoma of the lung in patients with stage I disease.
Authors: Kadota K. , Villena-Vargas J. , Yoshizawa A. , Motoi N. , Sima C.S. , Riely G.J. , Rusch V.W. , Adusumilli P.S. , Travis W.D. .
Source: The American Journal Of Surgical Pathology, 2014 Apr; 38(4), p. 448-60.
PMID: 24472852
Related Citations

Mesothelin overexpression is a marker of tumor aggressiveness and is associated with reduced recurrence-free and overall survival in early-stage lung adenocarcinoma.
Authors: Kachala S.S. , Bograd A.J. , Villena-Vargas J. , Suzuki K. , Servais E.L. , Kadota K. , Chou J. , Sima C.S. , Vertes E. , Rusch V.W. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2014-02-15 00:00:00.0; 20(4), p. 1020-8.
EPub date: 2014-02-15 00:00:00.0.
PMID: 24334761
Related Citations

Visceral pleural invasion does not affect recurrence or overall survival among patients with lung adenocarcinoma ¿ 2 cm: a proposal to reclassify T1 lung adenocarcinoma.
Authors: Nitadori J. , Colovos C. , Kadota K. , Sima C.S. , Sarkaria I.S. , Rizk N.P. , Rusch V.W. , Travis W.D. , Adusumilli P.S. .
Source: Chest, 2013 Nov; 144(5), p. 1622-31.
PMID: 23807749
Related Citations

Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller.
Authors: Nitadori J. , Bograd A.J. , Kadota K. , Sima C.S. , Rizk N.P. , Morales E.A. , Rusch V.W. , Travis W.D. , Adusumilli P.S. .
Source: Journal Of The National Cancer Institute, 2013-08-21 00:00:00.0; 105(16), p. 1212-20.
EPub date: 2013-08-21 00:00:00.0.
PMID: 23926067
Related Citations

Thyroid transcription factor-1 expression is an independent predictor of recurrence and correlates with the IASLC/ATS/ERS histologic classification in patients with stage I lung adenocarcinoma.
Authors: Kadota K. , Nitadori J. , Sarkaria I.S. , Sima C.S. , Jia X. , Yoshizawa A. , Rusch V.W. , Travis W.D. , Adusumilli P.S. .
Source: Cancer, 2013-03-01 00:00:00.0; 119(5), p. 931-8.
EPub date: 2013-03-01 00:00:00.0.
PMID: 23096929
Related Citations

Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor ß2 (IL-12Rß2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence.
Authors: Suzuki K. , Kadota K. , Sima C.S. , Nitadori J. , Rusch V.W. , Travis W.D. , Sadelain M. , Adusumilli P.S. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2013-02-01 00:00:00.0; 31(4), p. 490-8.
EPub date: 2013-02-01 00:00:00.0.
PMID: 23269987
Related Citations

Mesothelin-targeted immunotherapies for malignant pleural mesothelioma.
Authors: Villena-Vargas J. , Adusumilli P.S. .
Source: Annals Of Cardiothoracic Surgery, 2012 Nov; 1(4), p. 466-71.
PMID: 23977538
Related Citations