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Induction Chemotherapy, Extrapleural Pneumonectomy And Adjuvant Fast Neutron Radiationtherapy For Pleural Mesothelioma (Dmm)

Eric Vallières MD, , Karen Hunt MD, Keith Stelzer MD.

Extrapleural pneumonectomy (EPP) remains the most effective therapeutic modality to locally control DMM but both local and systemic recurrences are common. Effective induction chemotherapy and adjuvant neutron radiation therapy could potentially improve both local and systemic control and impact survival. This phase II trial evaluates the feasibility of induction cisplatin, methotrexate and vinblastine chemotherapy (PMV), EPP and adjuvant fast neutron radiotherapy (FNRT) in the treatment of DMM.

Patients with clinical stages I-III DMM, Karnofsky 80% or better and who have adequate cardiopulmonary reserves were given induction PMV followed by EPP and adjuvant whole hemithorax FNRT. Data was collected prospectively.

Twenty-three patients (19 M, 4F), ages 38 to 74, clinical IMIG stages I (10), II(6) and III (7) have initiated this protocol. This represents 62 % of all the patients evaluated during the same period in our Mesothelioma Multidisciplinary Clinic. Fourteen of these patients are completing their induction PMV. In the other 9, a clinical response to chemotherapy was seen in 7 patients, a radiological response in 5. All 9 patients have undergone EPP ( 6 right, 3 left). Gross positive margins were present in 3 patients, microscopic positive margins were identified in another 5. The only complete resection was in a patient with prechemotherapy sarcomatous histology who was NED at surgery. Histology was epithelial in 6, mixed or desmoplastic in 2 and sarcomatous in 1. The IMIG pathological stage distribution was: CR (1), stage III (5) and stage IV(3). There was no operative mortality and hospital stays ranged from 6 to 11 days. Delayed morbidity was major in 3 patients. Seven patients have completed the adjuvant FNRT, one patient received conventional RT and one patient was diagnosed with brain metastases 6 weeks after resection. Three patients have died, 2 of their DMM, both had biphasic histology, N2 disease at resection and neither had demonstrated a radiological response after PMV. The 6 remaining patients are alive at 35,29,17,16, 14 and 12 months post diagnosis. Five of the survivors have recurred (local 1, regional 1, systemic 3).

Conclusion: Induction PMV, EPP and FNRT appears safe in this early experience and provides excellent local control, even in higher T stage disease. Regional and systemic recurrences are however a problem. The survival of these high stage patients may be improved, longer follow-up and a larger experience are required.

Related: Patient selection criteria for extrapleural pneumonectomy