New Discoveries Toward Brain Cancer Recovery

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2012- Focus on Brain Cancer Conference:
Discovery to Recovery. In this blog, she discusses treatments for brain cancer.

Neurosurgery:  The Crux of Treatment for Brain Cancer

"The neurosurgeon's goal is take out as much of the tumor as possible safely, " says Steven Brem, MD, conference chair, and director of neurosurgical oncology.

"Personalized medicine has become something of a buzz work in medicine, but it is true for brain cancer patients,” says  Donald O'Rourke, MD, associate professor of neurosurgery.

Penn neurosurgeons are using improved imaging techniques for "neuronavigation."  This approach provides real-time, 3D views for the surgeon as he operates - allowing for maximum safe resection of the tumor and avoiding normal tissue.  This is particularly crucial in preserving language function and motor skills.

Radiation Therapy:  The Full Spectrum of Options

"Penn has the largest, most advanced proton facility in the world, one of only 10 in the United States.  We also have the unique advantage of having all of our radiation facilities integrated under one roof, "
Robert Lustig, MD, professor of radiation oncology.

Radiation therapy plays a key role in the treatment of most brain cancers.  Penn offers the full range of treatment modalities including one of only 10 proton facilities in the country.  Patients often are unsure of the relative benefits or indications for different kinds of radiation therapy, for example, protons vs. the gamma or cyber knife. 

Radiation therapy treatment decisions for brain tumors are highly individualized and need to be made in the context of multidisciplinary planning. 

Briefly stated, protons:

• Are more precise than conventional radiation therapy and do less damage to normal tissue
• Reduce side effects both short and long term 
• Deliver slightly more radiation to the tumor on a dose by dose basis
• Are effective in treating tumors near sensitive structures such as the spinal cord
• Can be used to "retreat" some patients with brain cancers

Dr. Lustig noted that Penn is now conducting clinical trials using protons for high-grade glioblastomas, grade III astrocytomas and pituitary adenomas, and will participate in an NCI-RTOG national study on protons for glioblastomas expected to begin soon.

He also noted that many patients encounter insurance issues in trying to get approval for proton therapy, although Medicare pays for most indications.

Stereotactic radiosurgery using the Gamma Knife® is another option for treating brain cancers.  Michelle Alonso-Basanta, MD, PhD, assistant professor of radiation oncology, explained that the original Gamma Knife was not designed to treat cancers, but that advances in technology and technique have made this a useful therapy for some patients with brain cancers.

"As with protons," she says, "we can deliver a very high dose of radiation to the target with little or no exposure of normal tissue to the radiation.  And, as with protons, the decision as to who will benefit from this approach is very individual."

Both stereotactic radiosurgery and protons offer the possibility of retreatment for patients who have undergone a previous course of radiation therapy and whose tumors have recurred.  In the past, these patients were not eligible for additional radiation therapy. 

Targeted Therapies: Changing Cancer Treatment

Penn Medicine has been a leader in immunotherapy research and in developing targeted vaccines for cancer for many years.  Bruce Levine, PhD, facility director, clinical cell and vaccine production facility describes work currently underway that involves activating T-cells, one of the mainstays of the body's defense system, to fight cancers. 

"If I could design T-cells to fight cancer," he says, "they would be potent, have a good memory, be persistent and numerous."

A new approach, developed at Penn, known as CAR (chimeric antigen receptor) T-cell therapy promises to be all of those things.  CAR uses a complex process to remove cells from the patients and own body and activate them to attack the tumor.  Penn is now in the process of developing clinical trials that will study the effects of CAR T cell therapy on glioblastomas with the EGRF v III mutation.

That mutation is the focus of work aimed at improving brain cancer treatment using chemotherapy as well.  Arati Desai, MD, MAS, is using bevacizumab (Avastin), a drug that inhibits blood vessel formation, in combination with another drug in patients with recurrent glioblastomas.  Phase II studies have demonstrated improved response rates and survival, although Desai acknowledges that some controversy exists about what those responses mean in terms of actual survival times.

Other clinical trials are aimed at attacking cancer cells from both the inside of the cell and the outside. 

These include approaches using

• Immunotherapy
• Combinations of drugs that target multiple pathways
• Drugs that affect the environment around the tumor
• Drugs that block the critical M Tors pathway
• Drugs that target factors known to influence prognosis, such IDH1 and MGMT

"There isn't going to be a single drug or agent that is going to work for everyone," says Desai.  "It's not going to be the same answer for every patient."

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Immunotherapy and Leukemia

A front-page story in the New York Times details the progress of a Perelman School of Medicine team in using genetically engineered versions of leukemia patients' own T cells to fight their cancer; an approach which has now been used in 12 patients, 9 of whom responded to the therapy -- including two children.

"Our goal is to have a cure, but we can't say that word," said the study's leader, Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn's Abramson Cancer Center.

He hopes the new treatment will eventually replace bone-marrow transplantation, an even more arduous, risky and expensive procedure that is now the last hope when other treatments fail in leukemia and related diseases.

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Gifts for Someone with Cancer

Carolyn Vachani, RN, MSN, AOCN, is an oncology advanced practice nurse at the Abramson Cancer Center. She has worked in the areas of medical hematology and oncology, bone marrow transplant, clinical research, radiation therapy and staff development. She is also the nurse educator for OncoLink.

Have you thought about holiday gifts for someone with cancer?

The holidays can be very stressful- particularly when you are already dealing with a cancer diagnosis or are the caregiver for someone with cancer. Perhaps you know someone in such a situation. Whether they are a family member, good friend or just the woman down the street you always pass when walking the dog, you may be thinking about their struggles this holiday season and want to show them you care. I encourage you to think outside the box of chocolates.

In my years of caring for and talking to people with cancer, I have never heard “so-and-so gave me the nicest box of chocolates.” What they do remember is the kind – and often free – gestures from people, no matter the time of year. A card with a kind note; a meal left on the front steps while they were at treatment; leaves raked when they just couldn’t do it themselves. Be the holiday helper who shops for and wraps all the kid’s gifts or decorates the house when the person had no energy to do it - remember to come back and un-decorate too! Deliver a holiday meal or invite them to yours.

You don’t need to spend money to show someone you care. Simple gestures can be so helpful - walk their dog, taking out the trash cans on trash day, call when you are going to the store and offer to pick up some items. A “gift” of your time and energy goes a long way to making someone feel cared about and special.

Have I got you thinking? Need more ideas? The OncoLink Holiday Survival guide has many more ideas for special gifts and shares survivor’s memorable gift stories.

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Cancer-fighting Recipe: Butternut Squash and Mac Casserole

This easy bake recipe gives a delicious, creamy appearance without the saturated fats of macaroni and cheese.

Butternut squash is the most nutrient dense of the winter squashes. It contains multiple carotenoids, Vitamin A, Vitamin C and fiber. The coconut milk adds to the creamy texture. Lower fat varieties are available if you are interested in cutting down the fat and calories.

Walnuts are my favorite nut as they are a good source of Vitamin E, Omega 3 fatty acids and melatonin. There are many ways to cut down on the total fat of this recipe if you are interested but remember, these are healthier fat choices. Substitute low fat coconut milk, sautee the onion in 1 Tbsp. of olive oil and decrease the walnuts to ¼ cup.

To save time, bake butternut squash whole when you have the oven on for any other reason. If butternut squash is already cooked and soft, you can save 20 minutes by blending the first 6 ingredients with an immersion blender. This makes a very creamy sauce.

Butternut Squash and Macaroni Casserole

Serves 8

Ingredients

• 2 tablespoons olive oil
• 1 large yellow onion, thinly sliced
• 1 butternut squash (about 2 lb.), peeled, seeded and cut in 1” cubes
• 1 can coconut milk
• Salt and pepper to taste
• 1 tb. Chopped sage
• ¾ lb. dried elbow macaroni
• ½ cup chopped walnuts
• ½ cup bread crumbs

Directions
Preheat oven to 350 degrees F. Lightly oil a 9x13” casserole dish; set aside.

Heat oil in a medium pot with the heat on medium. Add onions and cook, stirring often until soft (5-7 minutes). Add squash, coconut milk, salt and pepper and bring to a boil. Cover, reduce heat to medium low and simmer until squash is tender, about 20 minutes. Stir in sage and simmer 1 more minute. This part can be made ahead, up to 1 day in advance.

Meanwhile, bring a large pot of salted water to a boil. Add macaroni and cook until tender but still firm (about 8 minutes). Rinse in cold water, drain well and transfer to a large bowl. Transfer squash mixture to bowl with macaroni. Add walnuts and toss to combine. Transfer to prepared dish and top with bread crumbs. Bake until golden brown and hot (about 30 minutes).

Nutrition per serving: 400 cal, 21 grams of fat, 5 grams of fiber, 9 grams of protein

Recipe from Whole Foods

Debra DeMille, MS, RD, CSO is a nutritional counselor at the Joan Karnell Cancer Center. Debra has worked at Pennsylvania Hospital since 1988 with the last 12 years specializing in oncology. Debra guides individuals receiving chemotherapy and radiation as well as addressing survivorship issues including the use of integrative therapies.


She conducts cooking programs and group counseling sessions for cancer survivors.

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The Promise and Peril of Genetic Testing

Susan Domchek, MD, executive director of the Basser Research Center and an associate professor in the division of Hematology-Oncology in the Abramson Cancer Center was a guest on WHYY Radio's Radio Times, discussing advances in genetic testing.

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Immunotherapy for Lung Cancer

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2012- Focus on Lung Cancer Conference. In this blog, she discusses new ways in which lung cancer tumors are being used to create new treatments for lung cancer.

Demystifying the Immune System

"Lung cancer is a formidable foe with many ways of eluding the immune system--but we are developing multiple approaches to using immunotherapy as a treatment option." Gregory Beatty, MD, PhD

Our immune systems are sophisticated, highly evolved and multi-dimensional. They look for and attack invaders. They fight infections, heal wounds and maintain our body health. But do they recognize and fight cancer? And if not, why not?

The answer is complicated. The immune system does, at least in some instances, recognize and attack cancer cells, including lung cancer cells--but in many cases, it fails to eradicate these cells. New research indicates that cancer cells actually develop ways of co-opting the immune system, teaching it to help the cancer grow and spread. This says Dr. Beatty is "bad education," and the goal of immunotherapy research is to re-educate the immune system to attack cancer cells.

At Penn, researchers are using a number of approaches. These include:

• Cancer cells have the ability to produce STOP signals that prevent the immune system from recognizing them. One approach to immunotherapy is to develop specific antibodies that go after these STOP signals and block them. One example is the PD-1 blocking antibody.
• CAR-T or chimeric antigen receptors use specially engineered killer T-cells to attack cancer cells. These T-cells are harvested from the patients, go through an amazing process by which they are "re-programmed" to attack the patient's tumor, and then re-injected. The results for several cancers have been promising--with trials scheduled to begin for non small cell lung cancers.

Right now, there are no immunotherapy agents approved by the FDA to treat lung cancer, but clinical trials are underway in patients with advanced disease, and are planned as adjuvant therapy for patients who undergo potentially curative surgery as a means of reducing the risk if recurrence.

To learn more about immunotherapy clinical trials at Penn, call Abramson Cancer Center Clinical Trials Service Toll Free: 1-855-216-0098, Local: 1-646-354-4221 Monday through Friday, 8:30 am to 5:30 pm or email ACCStudies@emergingmed.com

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Brain Cancer Experts Behind the Scenes at the Abramson Cancer Center

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2012- Focus on Brain Cancer Conference. In this blog, she discusses the experts behind the scenes at the Abramson Cancer Center.

"For 10 years, we have been talking more about hope than progress, but in the last couple of years, we are seeing big differences using new drugs and targeted therapies. We aren't really sure why this is occurring, but we know that our mission is to move from discovery to recovery."- Steven Brem, MD, Conference Chair, and Director of Neurosurgical Oncology.

In 2012, 23,000 people will be diagnosed with cancers of the brain and spinal cord. In adults, 75 percent of those will be glioblastomas.

Cancer treatment today depends on having a team of experts, working together, pooling their knowledge and insight to develop the best care plan for every individual patient. Patients get to know their surgeons and medical oncologists, even their radiation therapists, but seldom interact with other members of the team whose contributions are critical.

The Focus on Brain Cancer Conference offered patients and family members the opportunity to hear from those experts, the pathologist, the radiologist, and in this instance, a scientist who works with mathematical models to understand brain cancer. Their talks were a clear indication of the progress being made in understanding brain cancers--advances that translate directly into improvements in treatment.

Pathologists Identify Genetic Subtypes of Brain Cancers

Maria Martinez-Lage, MD, opened the conference by explaining the information that pathologists use to identify and classify brain cancers. She noted that brain cancers are not staged like other cancers, but rather assigned a grade from I to IV, with four being the most common and most aggressive adult brain tumor, glioblastoma. She also noted that glioblastoma is no longer viewed as one disease--rather there are four subtypes characterized by different molecular profiles.

Pathologists now look for several key factors in diagnosing and categorizing glioblastomas. These include:

• IDH1 mutation: A gene mutation that occurs more often in lower grade tumor and indicates a favorable prognosis
• MGMT: A genetic mutation that occurs in some glioblastomas that is an indicator or whether a tumor will respond to chemotherapy
• ECFRvIII : A gene mutation found in some glioblastomas and other cancers that indicates a more aggressive tumor--but also responds to specific targeted therapy

This kind of information has a direct impact on the treatment decision-making process. Research is currently underway to find other genetic mutations that can be targeted. Penn has also opened a Center for Personalized Diagnostics a combined research and patient care facility that is focused on the next generation of gene sequencing for cancer.

The cause of glioblastoma is generally unknown. There are some very rare familial syndromes that increase the risk, and some association with toxins and high doses of ionizing radiation, but most cases occur without an identifiable cause.

Watch a video about how the Center for Personalized Diagnostics is changing the way tumors are targeted.

Radiologists Pinpoint Critical Differences in Tumors

MRIs are the mainstay of brain cancer diagnosis and treatment assessment--a reality illustrated by the fact that the great majority of patients at the Penn Medicine Conference have had 10 or more MRIs. MRIs provide more information than CT scans without using radiation. According to Ronald Wolf, MD,PhD new approaches to imaging, however, are yielding rich new information about biology, anatomy and functioning of brain cancers that is changing treatment for many patients. These include:

• Angiogenesis: The formation of blood vessels by the cancer
• Cellularity: The cellular composition of the tumor
• Metabolism: The rate at which the tumor is consuming nutrients
• Anatomy: The exact shape and location of the tumor

Why are these important? These factors help predict how the tumor will behave. A brain cancer with a high tumor blood volume, for example, is generally higher grade and more aggressive than those with lower blood volume. They are also more likely to be the tumors that are positive for the EGFRvIII mutation.

Powerful imaging tools also allow for more precise "mapping" of specific areas of brain, those that control motor skills or language--which guide the surgeon in removing as much of the tumor while sparing normal tissue.

"These new tools," says Dr. Wolf, "give us a more accurate clinical profile, which allow us to tailor treatment decisions to the individual."

"The Big Tent": Science and Medicine Today: Engineers, Physicists and Mathematicians for Brain Cancer Treatment

Most cancer patients don't think of engineers, physicists and mathematicians as having anything to do with their treatment, but today's medicine often involves scientists from a broad range of disciplines. Christos Davatzikas, Ph.D., is one of them, an engineer at Penn, who is developing sophisticated mathematical models of the location, grade, type and size of glioblastomas to help understand more precisely how these tumors grow. His analysis provides critical data that helps predict which brain cancers will recur. One key finding confirmed by Davatzikas's data is that certain parts of the brain are more likely to develop high grade, aggressive tumors than others.

"We are using this information to inform clinicians as well as patients," he says. " If we can predict recurrence, we can provide more effective therapy to patients who need it and stop ineffective therapy for patients who are not benefitting from it."

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