This phase II trial studies how well intensity modulated radiation therapy adjusted by positron emission tomography (PET) scanning together with combination chemotherapy works in treating patients with stage II-IV non-small cell lung cancer (NSCLC). Radiation therapy uses high energy x rays to kill tumor cells. In intensity-modulated radiotherapy, multiple beam angles and dozens of beam segments are used to deliver highly conformal radiation therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PET-adjusted IMRT together with combination chemotherapy may kill more tumor cells.
PRIMARY OBJECTIVES: I. To estimate the efficacy (based on post-treatment PET findings) of dose-painted intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy for locally-advanced non-small cell lung cancer (LA-NSCLC). SECONDARY OBJECTIVES: I. To estimate the efficacy (based on clinical endpoints including locoregional control \[LRC\], disease-free survival \[DFS\], and overall survival \[OS\]) of dose-painted IMRT with concurrent chemotherapy for LA-NSCLC. II. To evaluate the safety of dose-painted IMRT with concurrent and adjuvant chemotherapy for LA-NSCLC. III. To evaluate the utility of post-treatment PET/computed tomography (CT) imaging as a predictor of clinical outcomes following treatment with this novel approach. IV. To explore, in a preliminary manner, whether metabolomic markers in the blood and urine prior to and during the course of treatment are associated with treatment response, clinical endpoints, and treatment-related adverse events such as radiation pneumonitis. OUTLINE: RADIATION THERAPY: Patients undergo PET-adjusted IMRT or proton beam radiation therapy five days a week for 5 weeks. CONCURRENT CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 3 hours and paclitaxel IV over 1 hour once weekly for 5 weeks beginning week 1 of thoracic radiotherapy. CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy and when esophagitis and chemotherapy-induced neuropathy are grade 1 or less, absolute neutrophil count (ANC) \> 1500, and platelet count \> 100,000, patients may receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment may repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity at the discretion of the treating physicians. After completion of study treatment, patients are followed up at 12-16 weeks, 19 weeks, every 3 months for 2 years, and then every 6 months for a total of 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Given IV
Undergo PET-adjusted IMRT
Undergo PET-adjusted IMRT
Given IV
Undergo PET-adjusted IMRT
Undergo proton beam radiation therapy
Albert Einstein College of Medicine
The Bronx, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
Metabolic Response of All Pulmonary Lesions and Thoracic Lymph Nodes
Favorable response will be defined as having maximum SUV less than 6.0 on post-treatment PET/CT.
Time frame: Up to 16 weeks after completion of radiation therapy
Incidence of Grade >= 2 Radiation-induced Lung Toxicity, Scored Using Common Terminology Criteria for Adverse Events (CTCAE), Version (v.) 4
Incidence of grade \>= 2 radiation-induced lung toxicity, scored using Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4, will be presented as frequency and percentages.
Time frame: Up to 5 years
Incidence of Grade >= 3 Treatment-related Toxicity, Scored Using CTCAE, v. 4
Incidence of grade \>= 3 treatment-related toxicity, scored using CTCAE, v. 4, will be presented as frequency and percentages.
Time frame: Up to 5 years
Locoregional Progression-free Survival Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Kaplan-Meier survival plots will be produced. The survival probabilities will be presented.
Time frame: From study registration to date of local or regional disease progression or death, censored at the date of data collection, assessed at 1 year
Lung Cancer Cause-specific Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions A patient will be considered to have died from lung cancer if he or she had evidence of disease progression at any site and no direct evidence of other cause of death. Kaplan-Meier survival plots will be produced.
Time frame: From study registration to death directly from lung cancer, censored at the date of data collection, up to a maximum of 5 years
Overall Survival
Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for overall survival among the predictor variables.
Time frame: From study registration to death, censored at the date of data collection, assessed at 1 year
Progression-free Survival Assessed Using the RECIST Criteria
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables.
Time frame: From study registration to date of disease progression or death, censored at the date of data collection, assessed at 1 year
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