Rusch, Valerie W.

TPS9079 Background: Pleurectomy/Decortication (P/D) with neoadjuvant or adjuvant chemotherapy has become a common lung-sparing surgical approach for MPM. Adjuvant hemithoracic IMPRINT was developed at Memorial Sloan Kettering Cancer Center and safe in a multi-institutional phase II study, with promising survival outcomes. The National Cancer Institute (NCI) sponsored this phase III randomized cooperative group trial to test the efficacy of this lung-sparing trimodality approach for resectable MPM. Methods: Patients with newly diagnosed MPM amenable to P/D are enrolled and undergo P/D followed by adjuvant platinum/pemetrexed (preferred) or neoadjuvant chemotherapy followed by P/D. Patients are stratified by histologic subtype, resection status (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 will be 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). The target accrual is 150 patients. This study was activated on January 29, 2020. Over 20 institutions have already committed to opening the study which is open to all National Clinical Trials Network (NCTN) sites. Treatment planning guidelines and helpful hints for photon and proton therapy will be presented. Conclusions: NRG LU-006 (clinicaltrials.gov: NCT04158141 ) is open to accrual. This is the first NRG Oncology randomized phase III trial on MPM and evaluates the use of IMPRINT following lung-sparing P/D and chemotherapy. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI). Clinical trial information: NCT04158141.

Abstract Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high‐resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1‐asssociated protein 1 ( BAP1 ) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

Purpose The survival of patients with non–small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. Patients and Methods Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. Results From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). Conclusion In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.