Extrapleural Pneumonectomy Permits More Effective Radiotherapy Dose Delivery for Malignant Pleural Mesothelioma
Abstract & Commentary
Synopsis: Malignant pleural mesothelioma (MPM) is an uncommon tumor that carries a dismal prognosis. Its incidence is rising and is expected to continue climbing as more patients reach the end of the 35-40-year lag period between asbestos exposure and tumor development. Local failures occur early, and patients typically die of pulmonary complications. In contrast to the limited radiation dose that patients undergoing pleurectomy/decortication can receive by virtue of their remaining lung tissue, investigators at MSKCC found that removal of the entire contents of the affected hemithorax via extrapleural pneumonectomy (EPP) enabled them to deliver tumoricidal doses while limiting the dose to nearby critical structures. This, in turn, resulted in better local control rates.
Source: Yajnik S, et al. Int J Radiat Oncol Biol Phys. 2003;56:1319-1326.
Malignant pleural mesothelioma is a disease that typically is associated with up to an 80% local recurrence rate. Median survival is on the order of 4-18 months. Surgery alone does not control the disease. Efforts at resecting all gross disease by pleurectomy and decortication, followed by chemotherapy and/or radiotherapy, have not improved outcomes. Intrapleural chemotherapy and brachytherapy at sites of residual disease have not helped much. It has been widely recognized that external beam radiotherapy doses to the tumor bed in the lung were limited by the presence of residual ipsilateral lung tissue, making RT ineffective. Once the Lung Cancer Study Group reported that extrapleural pneumonectomy (EPP) offered a survival benefit over pleurectomy/decortication in 1991, it became possible to increase the adjuvant RT dose.1 This is because, using the EPP technique, the entire lung along with the pleura, diaphragm, and ipsilateral pericardium are removed, and a mediastinal lymph node dissection is usually performed. The ipsilateral chest wall, bronchial stump, diaphragmatic insertion points, mediastinum, and pericardium are then at risk for local recurrence and serve as the target structures for postoperative RT.
Yajnik and colleagues reported on 35 patients who were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1991-2001 with EPP and radiotherapy. Three-quarters of the patients had epithelioid tumors, while the remainder had other types of MPM. Mean age was 60 years (range, 9-75 years). Four patients had Stage I tumors, 11 Stage II, 19 Stage III, and 1 Stage IV. Radiotherapy commenced 3-6 weeks postsurgery and consisted of mixed electrons and 6 MV photons given AP/PA at 1.8 Gy per fraction for 30 fractions to a dose of 54 Gy (range, 45-54 Gy). The upper border was at the thoracic inlet (T1), the lower border was at the inferior aspect of L2, the lateral border was flashing the skin, and the medial border was either at the contralateral edge of the vertebral column if there were no positive lymph nodes, or 1.5-2 cm lateral to the edge if there was disease in the lymph nodes. The stomach and liver were blocked from the outset, and those portions of the thoracic cavity extending into the blocked area were covered with electrons. The heart was blocked after 19.8 Gy for tumors on the left, and electrons were used as above to cover the chest wall and diaphragm. Finally, the spinal cord was blocked at 41.4 Gy, and the remainder of the field was treated for an additional 12.6 Gy to 54 Gy.
At a median follow-up of 55 months (range, 17-85 months), there were 13/35 local failures (37%), including 2 chest wall failures and 3 skin failures away from drainage sites or scars. Five patients (14%) were alive without disease, 26 (74%) died of disease, 2 (6%) were alive with disease, and 2 (6%) were lost to follow-up. Toxicities were limited, with 6 patients requiring intravenous hydration during RT. One patient developed a bronchopulmonary fistula and empyema.
Yajnik et al concluded that EPP and RT to adequate doses are feasible and lead to higher local control than reported in the literature, while at the same time limiting the doses to critical structures such as the spinal cord, liver, stomach, esophagus, and heart. Diaphragmatic reconstruction must be anatomically correct so that the entire preoperative volume at risk is included within the fields. The single patient at MSKCC who was treated to T12 rather than L2 failed in the posterior costophrenic angle. Given the success of the above technique, a pilot trial testing the efficacy of induction chemotherapy is now being conducted, according to Yajnik et al.
Comment by Edward J. Kaplan, MD
In general, the obstacles to delivering an effective dose of radiation to structures inside the hemithorax are: limitations posed by the tolerance doses of the critical structures listed above, particularly the lung; intact mobile diaphragms; and proper delineation of the target volume. Following EPP, the removal of all ipsilateral lung tissue virtually eliminates the potential for pneumonitis, and reconstructed Gore-tex diaphragms exhibit no real respiratory excursion. This leaves target delineation as the last hurdle.
Ahamad and colleagues from M.D. Anderson Cancer Center (MDACC) recently published their institutional experience with a pilot study involving 7 MPM patients who were treated using an intensity-modulated radiotherapy (IMRT) approach.2 They collaborated directly with their thoracic surgeons, who had clipped areas within the hemithorax for RT targeting purposes. In contrast to the MSKCC study where clips were not routinely used, the MDACC paper pointed out that the surgeons adjusted their clipping patterns in a dynamic fashion as problems were encountered during CT-target identification with their radiation oncology colleagues. The MDACC investigators delivered 50 Gy with 6 MV photons to the hemithorax, followed by a boost to 60 Gy to areas with residual disease or positive margins. Acute toxicity was quite manageable. They found "better than expected" local control, with no local failures at a median follow-up of 13 months. Interestingly, they determined that it is fruitless to attempt to spare the ipsilateral kidney based on its proximity to the target volume. In a companion paper from MDACC by Forster et al,3 the MSKCC technique was criticized for only "occasionally" including the upper pole of one kidney. Like the MSKCC team, they cautioned against "abdominalizing" the pre-EPP diaphragmatic insertion in order to avoid truncating the RT target volume (ie, a "geographic miss").
It is encouraging to see that higher doses of RT can now be delivered safely to the hemithorax in patients who undergo EPP. As always, meticulous attention must be paid to designing the RT fields, both to avoid geographic misses and to avoid toxicity to critical structures. Undoubtedly, we will continue to learn more as data are accrued and the various planning and treatment techniques are refined.
Dr. Kaplan is Acting Chairman, Department of Radiation Oncology, Cleveland Clinic Florida, Ft. Lauderdale, FL; Medical Director, Boca Raton Radiation Therapy Regional Center, Deerfield Beach, FL
References
1. Rusch VW, et al. J Thorac Cardiovasc Surg. 1991; 102:1-9.
2. Ahamad A, et al. Int J Radiat Oncol Biol Phys. 2003; 55:768-775.
3. Forster KM, et al. Int J Radiat Oncol Biol Phys. 2003; 55:606-616.
Malignant pleural mesothelioma (MPM) is an uncommon tumor that carries a dismal prognosis. Its incidence is rising and is expected to continue climbing as more patients reach the end of the 35-40-year lag period between asbestos exposure and tumor development.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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