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The majority of patients treated aggressively for mesothelioma fail locally, and this often leads to their ultimate demise. As conventional chemotherapy has shown little activity in this disease, and surgical resection alone has not been efficacious as well, efforts have been directed at better multi-modality local control paradigms. Although it is known that mesothelioma can respond to radiation therapy, the use of conventional external beam radiation has not been helpful due to both the inability to provide an adequate dose over such a large area, and toxicity. Intensity Modulated Radiation Therapy (IMRT) will be used in this protocol in order to deliver therapeutically significant radiation doses (45 to 50 Gy for microscopic disease and 60 Gy for gross disease), while still sparing the nearby critical normal organs. IMRT has the ability to very closely conform radiation dose beamlet distributions to anatomic structures. The delivery of these beamlets, or IMRT fields, is achieved by dividing the field into 1x1 cm voxels and optimizing the dose to each centimeter cube of the patient.
Click here for an interview with Dr. Smythe on Current Therapeutical Approaches for Mesothelioma, particularly his trial of extrapleural pneumonectomy in conjunction with intensity modulated radiation therapy.
The patients will first be carefully screened as candidates for surgical resection (extrapleural pneumonectomy or EPP) with physiologic screening (cardiac and pulmonary function) and surgical staging (mediastinoscopy, laparoscopy). All histologies will be included, and patients can have ipsilateral, but not contralateral mediastinal lymph node disease. Careful marking of the true extent of the native diaphragm and any other areas felt to be at particular risk is performed intraoperatively, and the surgeon, radiation therapist and physicist perform radiation planning and review of planning radiographs as a multidisciplinary team. Following 5-10 weeks of recovery from surgery, the IMRT is administered to the patient over a 5 week period.
In a pilot evaluation of the protocol, 7 patients were treated with combination EPP/IMRT. Currently with more than 12 months median follow-up in this group there has been no evidence of local tumor recurrence in the radiation field, even though 6 of those patients were Dana-Farber Stage III.
Inclusion criteria for IMRT
- Patients must have undergone extrapleural pneumonectomy at M. D. Anderson Cancer Center.
- Patients must have a performance status >70 KPS.
- Patients must have adequate renal function in the contralateral kidney to tolerate obliteration of the ipsilateral kidney. This will be determined by renal scan, with more than 40% of the GFR contributed by the contralateral kidney.
- Patients must have normal liver function tests (no more than 50% elevation of SGOT, SGPT and Bilirubin) and no history of liver cirrhosis. If the primary tumor is left sided, cirrhosis is not a contraindication.
- Patients must be able to lie flat for the duration of the treatment planning sessions and treatment.
- Patients will have recovered from surgery, and have performance status >70 KPS. Typically this will be 3-5 weeks post-surgery.
- All patients not meeting the inclusion criteria will be excluded.
- Patients having parietal pleural stripping or chemotherapy prior to protocol entry
- Patients having previous radiation therapy to the low neck, thorax or upper abdomen.
- Patients with metastatic disease.
- Patients must not be oxygen dependent at the time of radiotherapy treatment planning.
- Patients requiring renal dialysis
Read about promising IMRT results in treatment of malignant mesothelioma.
Click here for further description of IMRT.
Criteria for extrapleural pneumonectomy.
If you would like more information about participating in Dr. Smythe's clinical trial on intensity modulated radition therapy please fill out this form: