No abstract

Oligometastatic cancer is characterized by a limited number of metastatic deposits. Compared with lung cancer patients who have more widespread disease, oligometastatic lung cancer patients have more favorable survival outcomes. Therefore, it has been hypothesized that local ablative therapy (LAT) directed at the metastatic deposits in addition to standard-of-care systemic therapy may further improve survival outcomes in oligometastatic lung cancer patients. One LAT modality that has been utilized in oligometastatic lung cancer is radiation therapy. In particular, ultra-hypofractionated radiotherapy, also known as stereotactic body radiotherapy (SBRT), has been shown to provide excellent local control with a favorable safety profile. Here, we reviewed the retrospective studies and prospective trials that have deployed radiation therapy as LAT in oligometastatic lung cancer, including randomized studies showing benefits for progression-free survival and overall survival with the addition of LAT. We also discuss the impact of targeted therapies and immunotherapy on radiation as LAT.

IMPRINT was developed at Memorial Sloan Kettering Cancer Center and found safe in a multi-institutional phase II study, with promising survival outcomes. CTEP approved a phase III randomized cooperative group trial (NRG LU-006) to evaluate the efficacy of this lung-sparing trimodality treatment approach for resectable MPM. Materials/Methods: Patients with newly diagnosed MPM amenable to P/ D are enrolled and undergo upfront P/D followed by adjuvant platinum/ pemetrexed chemotherapy (preferred approach) or neoadjuvant chemotherapy followed by P/D. Patients are stratified by epithelioid vs. biphasic histologic subtype, achievement of a macroscopic complete resection (R0/ 1 vs. R2), and center patient volume (≤10 vs. > 10 P/Ds per year). Within 8 weeks after completion of the second modality, patients are randomized 1:1 to undergo hemithoracic IMPRINT vs. no further therapy. All IMPRINT contours and treatment plans are centrally reviewed. A contouring atlas and treatment planning constraints for target structures and organs at risk, including acceptable and unacceptable variations and deviations, were developed. Photon and proton therapy are permitted. The primary endpoint of the study is overall survival. Secondary endpoints include local failure-free, distant-metastases free and progression-free survival, treatment-related toxicities (CTCAE v5.0) and change in quality-of-life (EORTC QLQ-C30 mean score changes at 9 months post randomization). Exploratory objectives include correlation of clinical/radiographic staging with pathologic stage, immunologic and pathologic biomarkers as predictors of response, the rate of R0/R1 vs. R2 resections, and EORTC QLQ-C30 and LC13 symptom scores changes over time. This study was activated on January 29, 2020. As of 02/2021,16 sites are approved and 46 sites are pending approval to open the study. Treatment planning guidelines and helpful hints for photon and proton therapy will be presented. Two patients have been accrued, and the target accrual is 150 patients. Results: TBD Conclusion: NRG LU-006 is now open to accrual. This is the first NRG Oncology randomized phase III trial on malignant pleural mesothelioma and evaluates the use of IMPRINT following lung-sparing P/ D and chemotherapy. Treatment planning aspects and current status will be presented.