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Targeting Mesothelioma

Meso

A Team of Experts Tackles a Formidable Foe

 

 A key component of Penn’s Mesothelioma Program is the weekly meeting of multidisciplinary specialists who review each case in detail and together come up with a treatment plan. Included in this group are (l. to r.) : James Stevenson, MD, of Thoracic Oncology; Keith Cengel, MD, PhD, of Radiation Oncology; Joseph Friedberg, MD, of Thoracic Surgery; and Dan Sterman, MD, of Pulmonary Medicine.

Cancers starting in the pleura – the membrane surrounding the lung and lining the chest -- are among the deadliest and most difficult cancers. They typically result in a life expectancy of less than a year. No one knows this better than Joseph Friedberg, MD, co-director of the Penn Mesothelioma and Pleural Program.

But that hasn’t stopped him and a group of dedicated specialists at Penn from joining forces to fight this disease.

“Most people think it’s untreatable…. but we don’t believe that’s the case.”

 

Anatomy 101

The mesothelium is a protective covering that protects most internal organs in the body. It comprises two layers: one immediately surrounds the organ and the second forms a sac around the bottom layer. In the chest, the area between the two layers is called the pleural space.

Meosthelioma, which is primarily caused by exposure to asbestos, grows as a sheet of malignant cells that envelope the interior of the chest. “There’s not a square inch in the chest cavity not involved with the cancer,” said Friedberg. “It’s everywhere.”  The disease’s invasive spread makes treatment difficult and often devastating for the patient.

According to Friedberg, conventional treatment – which can include radical surgery that takes out the lung, radiation, and chemotherapy --  does not cure this cancer. He said that in many medical centers, an extrapleural pneumonectomy (EPP) -- in which the affected lung is removed, along with the pleura, diaphragm and pericardium -- is the treatment of choice.  “It’s an enormous and complex procedure, but the disease still comes back,” he said. Even just removing the affected lung (a pneumonectomy) is fraught with risk. “It has the highest mortality rate of any elective surgery.”

Friedberg explained that many treatment programs need to remove the lung because they use radiation to destroy the microscopic cancer cells that remain behind. “To get enough radiation to kill cancer, you’d fry the lungs.”

In Penn’s program, which is based at Penn Presbyterian Medical Center, treatment usually includes lung-sparing surgery in which Friedberg removes the “rind of cancer” from the outer layer surrounding the lung and the lining of the chest, but keeps the affected lung intact. Immediately following surgery, the team begins photodynamic therapy (PDT), which combines a laser light source with non-toxic photosensitizing agents injected into the bloodstream. Unlike radiation, which passes through the body, PDT penetrates only a short distance which allows the lung to be preserved. The PDT treatment aims to eradicate the remaining microscopic disease, but, according to Stephen Hahn, MD, chair of Radiation Oncology, also seems to “trigger a patient’s own immune system to help fight cancer.” Penn is one of only two centers in the world where PDT is used to treat this disease.

Most patients coming to Penn also receive chemotherapy – whether they’ve had surgery or not.  If radiation is deemed necessary, it is used sparingly. “We put quality of life on equal footing with the benefit of the treatment,” Friedberg said. “Two years ago, we treated a patient in her 80s who’s now down in Florida playing golf. Having a lung removed has a significant impact on day-to-day living.”
Based on data he presented at the 2011 meeting of the Society of Thoracic Surgeons, Friedberg said, “Our results using lung-sparing surgery, PDT and chemotherapy appear to be as good as – if not better than --  doing a full EPP and radiation.”

It’s About the Patient, Period

A key component of Penn’s program is the Wednesday morning meeting of the multidisciplinary group of specialists who review each case in detail. Together they decide which treatments might work best.
“We don’t believe a program like ours exists anywhere else,” said Dan Sterman, MD, of Pulmonary Medicine, who co-directs the program with Friedberg. “Other mesothelioma programs in this country are usually dominated by a single specialty. Ours is a program of equals.”
“Everyone who comes to these conferences checks their ego at the door,” Friedberg agreed. “It’s about the patient, period.”

The crucial responsibility of collecting the clinical data for each Wednesday conference rests on Melissa Culligan, RN, BSN, the program’s director of Clinical Operations. “Her level of devotion to these patients and her commitment to them – which translates into an unfathomable amount of work --  is what made and makes this program possible,” Friedberg said.

After this early morning meeting, patients confer with each of the specialists -- that day -- to learn the treatment options. “This is unique – to see the surgeon, medical oncologist, radiation oncologist and pulmonologist all in one day, in one place,” Sterman said. “We tailor a treatment plan for each patient and then each of us discusses his role when we meet with the patient."

Friedberg stressed that patients make the final decision. “We inform them and help them understand the benefits and risks of everything available to them.”
And they do it all with compassion.  “What strikes me is the feedback I receive from the patients. They are astonished at the high level of compassion and care they receive from the doctors in our program,”  said Karen Mudrick, associate director of Operations and the program’s patient navigator. “They are so grateful to be offered the most advanced treatment options by a medical team who is dedicated to their overall well being.”

Promising Results in Clinical Trials

Another important component of Penn’s program – which treats patients with mesothelioma as well as other diseases of the pleural space --  is the easy access to clinical trials focusing on mesothelioma treatment. “Virtually any patient who comes in has access to a clinical trial,” said James Stevenson, MD, of Thoracic Oncology. “We encourage their participation. It could not only help them but can lead us to better treatments.”

Stimulating the body’s immune system to fight cancer plays a major role in some of the trials. “Combining gene therapy with chemotherapy is a big focus,” Stevenson said. “The tumor works to hide itself and this approach actually stimulates the body’s immune system to recognize the tumor as foreign. . .and reject it.”

“Data suggests that gene therapy, by itself, can be effective and chemo is effective, but neither provides cures,” Sterman said. “When we combined the two therapies in a mouse with mesothelioma, it cured the illness.” Penn is the only place in the world where the trial is being run. 
Another trial at Penn focuses on using an antibody to inhibit one of the proteins involved in the spread of mesothelioma cells called TGF-beta. “This protein sends a signal to cancer cells, causing them to grow,” said Stevenson. “The antibody is designed to attach to the protein after infusion which then cuts this signal and prevents the cancer from spreading. We’re still collecting results from this study and will be doing similar trials with novel and promising agents in the future.”

The immune system also plays a role in a clinical trial at Penn’s Clinical Cell and Vaccine Production Facility (CVPF) with Carl June, MD, director of Translational Research at the Abramson Cancer Center. T-cells (white blood cells) removed from the patient’s blood are genetically modified and reinfused to target mesothelioma cells. “We’re the first – and only – place in the world to offer this trial to patients,” Sterman said.

Stevenson said that patients come to their program from throughout the country and the world. “It just shows how much this type of program is needed for this type of disease.”

Although mesothelioma may remain incurable, there are ways to extend a patient’s life and make sure that the quality of life is good. Sterman compared it to the great strides made in treating HIV over the past few decades. “Twenty years ago, it was a death sentence if you contacted HIV. Today, people are living 20-25 years with it.”

“We’re bringing all the modalities to bear in fighting this disease,” Friedberg said. “We are slowly nudging mesothelioma towards being more of a chronic disease, not a lethal one.”

PDT-Lights Photodynamic therapy aims to eradicate remaining microscopic cancer but also seems to trigger a patient’s own immune system.

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