Current dose escalation regimens with and without chemotherapy have failed to achieve improved local control and overall survival over standard of care therapy to date. Difficulties with dose escalation have been largely due to dose limiting toxicities of surrounding normal organs, in particular to the normal lung parenchyma, and esophagus. Real time, online adaptive planning using magnetic resonance imaging (MRI) could achieve significant volume reduction of primary lung disease over the course of therapy, thereby reducing dose to normal structures, and providing a mechanism in which to dose escalate safely, and more effectively with accurate target delineation. The investigators hypothesize that MRI based adaptive planning will provide a novel method to dose escalate safely with acceptable organ at risk doses. In addition, further improvements in radiotherapy targeting accuracy, normal tissue avoidance, and conformality of target-tissue coverage will be achieved through the use of 4D real-time tracking which is derived by deformably registering daily MR and planning MR (MRsim) and Computed Tomography Simulator (CTsim) with advanced non-rigid image-registration tools.
This study is a single-arm phase II study of adaptive radiotherapy using ViewRay MRI based imaging in locally Advanced non-small cell lung cancer patients. Randomization is not applicable.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
ViewRay Magnetic Resonance Imaging
In the (week 5), all patients will have a week 5 MRI and Four-dimensional computed tomography (4D CT) for purposes of planning Phase II boost. Gross tumors \< 5 cm will receive a MR-based adaptive replanning Stereo boost of 80 Gy - 90 Gy (20 Gy-30 Gy in 5 fractions). Gross tumors \< 5cm will receive an MR-based adaptive replan fractionated boost to 74 Gy at 2.4 Gy/day. Individualized radiation therapy prescription to primary tumor will maintain organs at risk (OAR) constraints to lung including mean lung dose (MLD) \< 20 Gy with V20 \< 37%. Simultaneously, MRI-based adaptive replanning boost of 12 Gy in 5 fractions (2.4 Gy/day) will be given to gross lymph nodes. Final doses prescribed will be limited by doses to all OARs.
University of Miami
Miami, Florida, United States
Rate of Locoregional Failure/Progression (LRF/LRP) in Study Participants Receiving Protocol Therapy.
MRI-based adaptative radiation planning can provide a method for dose escalation to improve locoregional Failure (LRF/LRP) rates at 2 years in study participants. Locoregional failure/progression (LRF/LRP) will be defined as development of progressive lung cancer centered within 1 cm from the initial planning target volume (PTV). Progressive disease in any of the 14 nodal stations will be considered as regional recurrence. Progression will be assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. with integration of MRI/CT.
Time frame: Up to 2 Years After Protocol Therapy
Rate of Severe Treatment-Induced Toxicity
Rate of severe (grade 3 CTCAE, v.4) radiation-induced lung toxicity (RILT) and other severe adverse events, including grade 3+ (CTCAE, v.4) esophagitis, or grade 2 pericardial effusions, or any grade cardiac adverse events related to chemo-radiation using MRI-based adaptive planning vs. historical controls using conventional plans.
Time frame: Up to 2 Years Post-End of Protocol Therapy
Rate of Overall Survival (OS) in Study Participants
Rate of overall survival in study participants using MRI-based adaptive planning vs historical controls. Overall survival is defined as the length of time from the start of treatment that study participants are still alive.
Time frame: Up to 3 years after protocol therapy.
Rate of Progression-Free Survival (PFS) in Study Participants
Rate of progression-free survival in study participants using MRI-based adaptive planning vs historical controls. Progression-Free Survival (PFS) is defined as the length of time that passes from the start date of protocol therapy until the date on which disease "progresses" or the date on which the participant dies, from any cause. Disease progression will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria.
Time frame: Up to 3 years after protocol therapy.
Rate of Lung Cancer-Specific Survival
Rate of Lung Cancer-specific survival in study participants using MRI-based adaptive planning vs historical controls. Lung cancer-specific survival is defined as the length of time that passes from the date of diagnosis or start date of protocol therapy until the date of death from lung cancer.
Time frame: Up to 3 years after protocol therapy.
Comparison of Gross Tumor Volumes (GTV) defined by MRI vs. FanBeam CT (FBCT) at CT Simulation and at each adaptive planning time point.
Gross tumor volumes (GTVs) at a specific time point between MRI and Fan Bean CT will be compared using Mann-Whitney test.
Time frame: Daily Up to 5 weeks after start of protocol therapy
Development of a Database consisting all Daily MR data sets to support further research.
Potential applications include determination of optimal adaptive planning frequency and the benefits of basing IGART on 4D anatomic datasets derived from deformably registering daily MR and planning FBCT and MR datasets.
Time frame: Up to 5 years
Predictivity of Volumetric Changes in MRI Imaging for Locoregional failure/progression (LRP) and Organs at Risk (OARs) toxicity.
Predictivity of volumetric changes in MRI imaging for LRP and OAR toxicity will be assessed using time-dependent receiver operating characteristic (ROC) method and regular ROC method, respectively.
Time frame: Up to 5 years
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