Short Neoadjuvant Hemithoracic IMRT for MPM

The study is a phase I/II prospective single cohort clinical feasibility study. 100 patients with early stage resectable malignant pleural mesothelioma will be enrolled into the study. Patients will have a baseline PET scan. Patients on the study will receive IMRT for approximately 1 week of 5 daily treatments. 1 week post-RT, they will proceed with an extrapleural pneumonectomy. If the mediastinal lymph nodes that are removed during surgery are positive for tumour cells, 3 cycles of chemotherapy, consisting of raltitrexed and cisplatin OR Pemetrexed and cisplatin, will be given 6-12 weeks post-surgery. Before and during treatment, side effects will be assessed. After treatment, follow up visits will be conducted every 1 to 2 months for the first year, and every 3 months for the second year. At each visit, a history and physical examination will be performed and ECOG performance status will be assessed. Routine tests will include CBC, liver profile, creatinine and chest x-ray. CT thorax and abdomen will be done at 3, 6, 12, 18, and 24 months. Additional test may be done at the discretion of the oncologist if the patient becomes symptomatic. The study will evaluate the feasibility and safety of short pre-operative RT, and may help confirm the intraoperative seeding hypothesis. Preoperative RT may also reduce the risk of both local and distant spread and, ultimately, improve overall survival. By shortening overall treatment time, it may also improve patient compliance and convenience. We may be able to give chemotherapy only to patients that are at highest risk and avoid it in others.

Inclusion criteria

• ECOG performance status of 0-2
• Good pulmonary function precluding radiation therapy (FEV>1 L or >40% predicted or DLCO >45% predicted)
• Any patient wiht a new histological diagnosis of malignancy pleural mesothelioma (MPM). Sarcomatoid or biphasic histologies can be included but will be analyzed separately due to their poor prognosis
• Stage T1-2N0M0 based on conventional investigations and tests. Selected stage T3N0M0 may be included at the discretion of the surgeon if deemed resectable.
• Suitable for combined modality therapy
• Informed consent

Exclusion criteria

• Distant metastatic disease
• Previous thoracic irradiation
• Serious non-malignant disease (e.g. cardiovascular, pulmonary, systemic lupus erythematosus (SLE), scleroderma) which would preclude definitive radiation treatment
• Previous chemotherapy for this or concurrent malignancy
• Previous concomitant malignancies except for patients with non-melanoma skin cancer, contralateral non-invasive breast cancer, prostate cancer treated with curative intent or carcinoma in situ of any other site. In addition, patients with invasive cancers treated more than 3 years previously and without evidence of recurrence will be eligible
• Women who are currently pregnant or lactating