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Grant Details

Grant Number: 1R21CA164568-01A1 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: 2012
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Abstract

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. PUBLIC HEALTH RELEVANCE: Detection of early stage lung cancer is anticipated to increase necessitating more accurate predictive instruments to identify patients at higher risk for recurrence. In this proposal, we combine our expertise of pathological, cytological and microRNA analyses to develop and validate a comprehensive risk model to identify patients at a higher risk for recurrence for aggressive surveillance or intervention.

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Publications

Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence.
Authors: de Biasi AR, Villena-Vargas J, Adusumilli PS
Source: Clin Cancer Res, 2014 Nov 1;20(21), p. 5384-91.
EPub date: 2014 Sep 9.
PMID: 25204552
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Recent advances and clinical implications of the micropapillary histological subtype in lung adenocarcinomas.
Authors: Lee MC, Buitrago DH, Kadota K, Jones DR, Adusumilli PS
Source: Lung Cancer Manag, 2014 Jun 1;3(3), p. 245-253.
PMID: 25202339
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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 YC, D'Angelo SP, Moreira AL, Kuk D, Sima CS, Riely GJ, Arcila ME, Kris MG, Rusch VW, Adusumilli PS, Travis WD
Source: Am J Surg Pathol, 2014 Aug;38(8), p. 1118-27.
PMID: 25029118
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Translational immunotherapeutics: chemoimmunotherapy for malignant pleural mesothelioma.
Authors: Adusumilli PS
Source: Cancer, 2014 Nov 1;120(21), p. 3268-71.
EPub date: 2014 Jul 2.
PMID: 24989696
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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 KM, Sima CS, Finley DJ, Rusch VW, Adusumilli PS, Travis WD
Source: J Thorac Oncol, 2014 Aug;9(8), p. 1126-39.
PMID: 24942260
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Using Frozen Section to Identify Histologic Patterns in Stage I Lung Adenocarcinoma ? 3 cm: Accuracy and Interobserver Agreement.
Authors: Yeh YC, Nitadori JI, Kadota K, Yoshizawa A, Rekhtman N, Moreira AL, Sima CS, Rusch VW, Adusumilli PS, Travis WD
Source: Histopathology, 2014 May 29;null, p. null.
EPub date: 2014 May 29.
PMID: 24889415
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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 CS, Riely GJ, Rusch VW, Adusumilli PS, Travis WD
Source: Am J Surg Pathol, 2014 Apr;38(4), p. 448-60.
PMID: 24472852
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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 SS, Bograd AJ, Villena-Vargas J, Suzuki K, Servais EL, Kadota K, Chou J, Sima CS, Vertes E, Rusch VW, Travis WD, Sadelain M, Adusumilli PS
Source: Clin Cancer Res, 2014 Feb 15;20(4), p. 1020-8.
EPub date: 2013 Dec 13.
PMID: 24334761
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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 YC, Sima CS, Rusch VW, Moreira AL, Adusumilli PS, Travis WD
Source: Mod Pathol, 2014 May;27(5), p. 690-700.
EPub date: 2013 Nov 1.
PMID: 24186133
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Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller.
Authors: Nitadori J, Bograd AJ, Kadota K, Sima CS, Rizk NP, Morales EA, Rusch VW, Travis WD, Adusumilli PS
Source: J Natl Cancer Inst, 2013 Aug 21;105(16), p. 1212-20.
EPub date: 2013 Aug 7.
PMID: 23926067
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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 CS, Sarkaria IS, Rizk NP, Rusch VW, Travis WD, Adusumilli PS
Source: Chest, 2013 Nov;144(5), p. 1622-31.
PMID: 23807749
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Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor ?2 (IL-12R?2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence.
Authors: Suzuki K, Kadota K, Sima CS, Nitadori J, Rusch VW, Travis WD, Sadelain M, Adusumilli PS
Source: J Clin Oncol, 2013 Feb 1;31(4), p. 490-8.
EPub date: 2012 Dec 26.
PMID: 23269987
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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 IS, Sima CS, Jia X, Yoshizawa A, Rusch VW, Travis WD, Adusumilli PS
Source: Cancer, 2013 Mar 1;119(5), p. 931-8.
EPub date: 2012 Oct 23.
PMID: 23096929
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