CHICAGO, IL-Despite previous pessimism about the efficacy of surgery in mesothelioma, Harvey Pass, MD, was optimistic about current trials in which novel therapies have complemented pleurectomy or extrapleural pneumonectomy surgical procedures. "There's a wealth of translational novel approaches in this disease that can compliment the surgery--so I'm not ready at this point to say that surgery doesn't have a role here--specifically since the mortality rates for this surgery are very reasonable." According to Dr. Pass, "these are times when the newer adjuvants are showing better efficacy than before--and, there are molecular innovative pathways that are being exploited, that I think, will go hand in hand with surgery."

In particular, Dr. Pass, is excited about taking the SV40-mesothelioma association to translational therapies with a new SV40 vaccine under development by Michael Imperiale, PhD, at University of Michigan Medical School, Ann Arbor. Dr. Pass, Professor of Surgery and Oncology, Karmanos Cancer Institute, Detroit, is Principal Investigator for a phase I dose-escalation study, funded through an NCI grant under the Rapid Access to Intervention Development (RAID) mechanism. The clinical trial will evaluate the immunization of mesothelioma patients, using a vaccinia construct containing a portion of SV40 T antigen. This will be the first attempt to study the vaccine's efficacy and look at the systemic immune responses in these patients. Dr. Pass hopes to eventually add other complimentary therapies to the vaccine approach. The vaccine intended for use in the clinical trial is currently in development, as well as tests to monitor immunologic parameters during the trial. The institutions involved in the trial will inlude the Karmanos Cancer Institute of Wayne State University, the Cardinal Bernardin Cancer Center of Loyola University, University of Michigan Cancer Center, and the Robert W. Franz Cancer Center of the Providence Portland Medical Center.

Dr. Pass also pointed to other possibilities for therapies to compliment surgery: "You could do upfront therapy like we do with lung cancer--the data will be out on promising agents like gemcitabine/platinum and MTA [multitargeted antifolate]--interoperative therapies like hyperthermic perfusions in the chest are being evaluated--new drugs [that are] given to the chest postoperatively--thorascopic approaches using gene therapy-- or clones of gene therapy, in which mesothelioma epitopes or antigenic foci are specifically targeted--photodynamic therapy--and postoperative adjuvants like the new cytotoxic drugs or antiangiogenesis agents." Hopefully, the introduction of new complimentary therapies will combat the nihilism with which mesothelioma has been so commonly associated, said Dr. Pass. Dr. Pass was straightforward about the absence of real advances in surgery, itself, but discussed the difficulties of mesothelioma surgery and his approach to overcoming some of these challenges. Dr. Pass explained that staging the disease is difficult. "You stage the patient as best you can by looking at the CT scan, but you also stage patients, functionally, by making sure that their cardiopulmonary reserve is okay," said Dr. Pass. Although great efforts have been made to create an internationally uniform staging system, especially those efforts by Valerie Rusch, MD (Please see table), this staging system is essentially a postsurgical staging system that is not very useful to surgeons, and it is also complicated by the fact that surgeons do not operate on many of these cases. "You need a staging system that is defined by observable criteria--That's why my interest has been in looking at the volumetrics of the tumor," said Dr. Pass.

According to Dr. Pass, criteria like the T cell status and the volume of the tumor can predict the stage that is ultimately determined from the postoperative pathological staging system. For instance, Dr. Pass found that a very bulky tumor generally indicates a patient has stage III mesothelioma, with an increased possibly for lymph node involvement or invasion through the diaphragm. Detection of cancerous cells by lymph node biopsy is extremely rare--Dr. Pass explained that with mesothelioma, "every once in a while you will have an obvious lymph node that you can biopsy." However, unlike lung cancer, positive lymph nodes are usually inaccessible for biopsy in mesothelioma patients.

As for other prognostic indicators, Dr. Pass underscored the importance of PET scanning. In PET scans, the uptake value of 18 F-Fluorodeoxyglucose may be a predictor of survival. Although PET scans may be very useful in the future, currently, it is difficult to use PET scanning, since reimbursement is unlikely under protocol restrictions.


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