Lung cancer is a leading cause of cancer death in the United States and worldwide. One of the recent breakthroughs in lung cancer treatment was the discovery of the somatic activating mutations of the epidermal growth factor receptor (EGFR) tyrosine kinase domain in non-small cell lung cancer (NSCLC), which is associated with a dramatic clinical response to EGFR inhibitors such as gefitinib and erlotinib. Erlotinib is particularly effective in patients with EGFR mutations. However, most patients with initial responses to erlotinib treatment eventually relapse due to acquired resistance to erlotinib. The purpose of this proposal is to analyze chronological changes in tumor size and volume in advanced NSCLC patients treated with erlotinib in clinical trials at Dana-Farber Cancer Institute, and determine if the tumor volume detects relapse caused by acquired resistance earlier than the tumor size does. If this is proven, tumor volume can be used as the primary marker for monitoring response to therapy instead of the conventional marker, tumor size. Early detection of acquired resistance to erlotinib by tumor volume analysis will allow oncologists to change therapeutic regimen for prolongation of progression-free survival. We also aim to determine if the initial proportional decreases in tumor size and volume correlate with progression-free survival and overall survival of the patients. If this is the case, tumor volume measured by CT can be used as a biomarker for prognosis. We will also determine if the tumor size and volume changes correlate with genomic changes in circulating tumor cells and free plasma DNA in advanced NSCLC patients. Genomic analysis of circulating tumor cells and free plasma DNA in NSCLC is an emerging non-invasive technique which allows for frequent assessment of genomic changes during therapy. The study will be performed using data collected in phase II prospective clinical trials of erlotinib in advanced NSCLC patients at the Dana-Farber Cancer Institute. Data includes chest CT examinations performed every eight weeks and EGFR mutation analysis. Tumor size and volume will be measured using a commercially available, Food and Drug Administration (FDA) approved volume analysis software. Changes of tumor size and volume will be calculated, and will be correlated with clinical outcome and genomic analysis results. The long term goal of the project is to determine the imaging parameters that most efficiently predict acquired resistance to erlotinib by integrating the genomic information into the tumor volume analysis, in order to optimize the therapeutic benefit of erlotinib and contribute to the prolongation of survival in lung cancer patients.

Public Health Relevance

Lung cancer is a leading cause of cancer death in the United States and worldwide needing more effective treatment options. The epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, has emerged as an attractive therapy for non-small cell lung cancer with a dramatic clinical response;however, most patients with initial responses eventually relapse due to acquired resistance. We aim to perform detailed chronological analysis of tumor size and volume in correlation with genomic information obtained from biopsy specimens, circulating tumor cells, and plasma DNA in lung cancer patients treated with erlotinib for early detection of resistance to erlotinib and prolongation of survival.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Subcommittee G - Education (NCI)
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Lim, Susan E
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Brigham and Women's Hospital
United States
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Putman, Rachel K; Gudmundsson, Gunnar; Araki, Tetsuro et al. (2017) The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes. Eur Respir J 50:
Nishino, Mizuki; Sacher, Adrian G; Gandhi, Leena et al. (2017) Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib. Eur J Radiol 88:15-20
Nishino, Mizuki; Giobbie-Hurder, Anita; Manos, Michael P et al. (2017) Immune-Related Tumor Response Dynamics in Melanoma Patients Treated with Pembrolizumab: Identifying Markers for Clinical Outcome and Treatment Decisions. Clin Cancer Res 23:4671-4679
Nishino, Mizuki; Hatabu, Hiroto; Sholl, Lynette M et al. (2017) Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care. Radiographics 37:1371-1387
Chong, Curtis R; Bahcall, Magda; Capelletti, Marzia et al. (2017) Identification of Existing Drugs That Effectively Target NTRK1 and ROS1 Rearrangements in Lung Cancer. Clin Cancer Res 23:204-213
Araki, Tetsuro; Yanagawa, Masahiro; Sun, Fangui Jenny et al. (2017) Pleural abnormalities in the Framingham Heart Study: prevalence and CT image features. Occup Environ Med 74:756-761
Nishino, Mizuki; Ramaiya, Nikhil H; Hatabu, Hiroto et al. (2017) Monitoring immune-checkpoint blockade: response evaluation and biomarker development. Nat Rev Clin Oncol 14:655-668
Araki, Tetsuro; Putman, Rachel K; Hatabu, Hiroto et al. (2016) Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med 194:1514-1522
Araki, Tetsuro; Nishino, Mizuki; Gao, Wei et al. (2016) Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking. Eur Radiol 26:15-24
Khandelwal, A; Sholl, L M; Araki, T et al. (2016) Patterns of metastasis and recurrence in thymic epithelial tumours: longitudinal imaging review in correlation with histological subtypes. Clin Radiol 71:1010-7

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