Despite these advances in surgical technique and refinement in prognostication and patient selection, the unfortunate fact remained that nearly all patients eventually died of their disease within 10 years of the operation. Recurrences appeared to result by direct extension from the ipsilateral hemithorax. Therefore, in the second half of the 1990s, the BWH group embarked on a new approach to multimodality therapy.
The major treatment plan of the previous 10 years had started with EPP because mesothelioma was predominantly a locoregional disease, and much of the early morbidity was from local spread. Since most patients died as a result of the primary cancer invading the diaphragm, chest wall, and mediastinal organs, initial surgical debulking was chosen prior to the initiation of chemotherapy in order to reverse the aggressive natural progression of this disease.
In 1997, Baldini et al.15 published a detailed retrospective review of 49 patients who underwent EPP and some combination of adjuvant chemotherapy and/or radiotherapy with a focus on defining patterns of failure. In this series, overall median survival was 22 months and 3-year survival, 34%. Resection margins were microscopically positive in 61% of patients and lymph nodes positive in 29%. Of the 54% of patients with recurrences, 67% percent had the first recurrence within the ipsilateral hemithorax, and 50% had recurrence at some time within the abdomen.
The potential role of intracavitary chemotherapy as a method of improving local regional control had been studied previously in a variety of abdominal malignancies. The local application of chemotherapy allows high cytotoxic levels to reach residual tumor cells by diffusion without the side effects of high dose systemic chemotherapy. Intracavitary chemotherapy with or without hyperthermia had been favorably reported in the literature.
Alberts et al.16 published a prospective randomized trial in The New England Journal of Medicine in 1996. Intraperitoneal cisplatin was compared to intravenous cisplatin in patients with stage III ovarian cancer following cytoreductive surgery. Among the 654 randomized patients, the estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months) than in the group receiving intravenous cisplatin (41 months).
The decision to design a phase I dose escalation trial of heated intraoperative cisplatin at the time of EPP had been supported by the BWH, the DFCI, and the leadership of all professional groups who would be involved in patient care. The obstacles to be overcome were formidable. Protocols to maximize both patient and staff safety were designed by a multidisciplinary “heated chemotherapy team” which met once a week to develop guidelines for this novel therapy. Ideas were actively sought from surgeons, anesthesiologists, pharmacists, nurses, scrub technicians, medical oncologists, and respiratory therapists to design the method of drug delivery and disposal in the operating room.
Radical pleurectomy is an attractive alternative for patients who are unsuitable for EPP. This includes patients with a decline in their functional status and elderly patients. A radical pleurectomy leaves the lung, but can remove the central portion of the diaphragm and the ipsilateral pericardium. The technique is well described by Dr. Flores in Chapter 121.
Innovative treatments also include the use of photodynamic therapy as an adjuvant treatment following EPP. Dr. Joseph Friedberg has developed this technique and provides details in Chapter 124.
The development of new chemotherapeutic agents (Chapter 117) with better response rates suggests the potential role of using these agents in a neoadjuvant manner for advanced stage disease. Dr. Walter Weder has been an articulate spokesman of this technique and provides his data in Chapter 125.
The low morbidity associated with thoracoscopic evaluation of the diseased pleural space has opened a new treatment paradigm for malignant effusions, irrespective of cause. A thoracoscope allows the breakdown of loculations and complete drainage of the effusion for palliation of symptoms, provides sufficient histologic material for a definitive diagnosis, and allows therapeutic intervention for long-lasting palliation of symptoms. This aspect of malignant pleural disease is described well in Chapters 119 and 120.