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The Latest in Pulmonary Care

1.Pulmonary Arterial Hypertension Trials

Much work is yet to be done in the fight against the chronic disease of pulmonary arterial hypertension (PAH). Currently, there are eight FDA-approved therapies for PAH, belonging to the classes of endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and prostacyclin analogues. Although these therapies can lower blood pressure in the lungs, improve heart function, and enhance quality of life, none of them is curative. 

Murali Chakinala, MD, a Washington University pulmonologist at Barnes-Jewish Hospital, heads several clinical trials of new therapies and new strategies for the treatment of PAH. Chakinala is an associate professor of medicine in the Division of Pulmonary and Critical Care Medicine and director of the Washington University Pulmonary Hypertension Center.

Some of the ongoing investigations include use of two simultaneous oral therapies (bosentan in conjunction with sildenafil), use of a novel oral version of a drug, treprostinil, that has only been available as a continuous infusion, and application of newer investigational agents (for example, macitentan and cicletanine). Additionally, an existing chemotherapeutic agent (imatinib) is also being investigated in PAH. Some of these studies are long-term and designed to demonstrate an improvement in clinical outcomes.

2. Specialized Radiation for Batter Cancer Treatment

Stereotactic body radiation therapy (SBRT) represents a substantial paradigm shift in radiation therapy for patients with stage I non-small cell lung cancer who are not candidates for surgical resection. Similar to Gamma Knife® treatment for tumors and other abnormalities in the brain, SBRT is performed at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine for isolated cancerous lesions in the lung, liver and spinal column.

Jeffrey Bradley, MD, associate professor of radiation oncology and director of the new Kling Center for Proton Therapy, specializes in treating lung and esophageal cancer and is an international expert in the application of SBRT. When the proton center opens in 2011, it will be the first single-vault proton therapy center in the country.

“Stereotactic radiation therapy is a very easy treatment for patients who have been turned down for surgery, and the side effects are very minimal,” Bradley says. “Studies show this radiation is very effective at killing cancer cells. We are able to kill the cancer that we treat 90 percent of the time.”

Stereotactic radiation therapy uses multiple planar and non-coplanar beams to precisely deliver a high dose of radiation to one or two small targets. Whereas threedimensional conformal radiation therapy for lung cancer generally consists of six to seven weeks of treatment, SBRT assumes a hypofractionated scheme, delivering the dose typically in three to five treatments using either the Varian Trilogy® system or the TomoTherapy® Hi-Art® treatment.

With its built-in CT scanning equipment, the Trilogy® unit allows radiation oncologists to identify tumors and map their locations. The radiation oncologist then aims approximately 10 to 12 radiation beams at the tumor’s center. The unit is also equipped with sophisticated software that can account for breathing motion, making it ideal for tumors that move during treatment, such as those in the lungs or liver. The TomoTherapy® unit also offers on-board CT scanning capabilities. It can deliver SBRT around critical organs, such as to a tumor in the spine, where the radiation dose needs to curve around the spinal cord.

3. Recurrent Lung Vaccine Trial

A vaccine designed to prevent the recurrence of lung cancer is being tested in centers around the world, including the Siteman Cancer Center. The vaccine stimulates the immune system to destroy cells that carry a tumor-specific antigen called MAGE-A3. This antigen is not present in normal tissue but is found in several cancer types, including 35 percent to 50 percent of cases of the most common type of lung cancer, non-small cell lung cancer.

The MAGE-A3-based vaccine answers a need for a highly efficient and safe therapy for patients who have undergone conventional treatment for a primary tumor but are at a high risk of relapse.

“The vaccine takes advantage of the immune system’s built-in ability to eliminate foreign materials and harmful cells,” says Bryan Meyers, MD, a Washington University thoracic surgeon at Barnes-Jewish Hospital. Meyers, the Patrick and Joy Williamson Endowed Chair in Cardiothoracic Surgery and chief of general thoracic surgery, heads the vaccine trial at the School of Medicine.   “This natural process has few side effects, unlike traditional treatments such as chemotherapy or radiation therapy.”  

Known as the MAGRIT (MAGE-A3 as Adjuvant Non-Small Cell Lung Cancer Immunotherapy) trial, the study will test the vaccine to determine whether it can prolong survival by delaying or preventing recurrence of lung cancer. The study involves more than 400 centers in 33 countries, and study leaders hope to enroll 2,270 patients.

The trial is open to people with stage IB, II or IIIA non-small cell lung cancer with MAGE-A3 positive tumors. Participants must have undergone complete surgical removal of their tumors within six weeks of beginning the trial.

The vaccine contains MAGE-A3 antigen particles along with compounds that cause inflammation. The inflammation helps alert the immune system to the antigen and activate killer T-cells that can eradicate cells with the antigen on their surface. Only cancer cells have the antigen.

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