Waging War On Cancer

With the opening of the Roberts Proton Therapy Center, Penn Medicine added another weapon in the battle against cancer. Proton therapy allows doctors to focus a very precise beam of radiation directly at the tumor, while sparing most of the surrounding tissue.

“Proton therapy is another tool to help us fight cancer, providing a more advanced way to target the tumor,” said Stephen Hahn, MD, chairman of radiation oncology at Penn. “It can be integrated with chemotherapy and/or surgery to provide truly personalized care. Proton is a great fit with the other cancer treatment options available at Penn.”

Every Option for Fighting Cancer
A key to successful treatment is having the best possible tools to provide personalized treatment for every patient. Proton therapy joins a cancer treatment option that is available in only a few places around the world with the services of Penn's Abramson Cancer Center, a NCI-designated Comprehensive Cancer Center.

The goal of cancer treatment is to eliminate the cancer and prevent recurrence. Because cancers are different, the effectiveness of the primary therapy modalities — surgery, radiation and chemotherapy — can vary in battling the disease. However, these various cancer therapies may be used in combination for added effectiveness. Their use alone or in combination largely depends on the type of cancer, the stage of the tumor and patients’ medical conditions. Some of the treatments available at Penn are:

• Bone marrow transplant.
• Chemotherapy.
• Hormone therapy.
• Immunotherapy, stimulating patients’ immune systems to fight cancer cells.
• Molecularly targeted therapy.
• Radiation therapy, including Gamma Knife^®, IMRT, Mammosite^®, photo-dynamic therapy and proton therapy.
• Surgery, including robotic-assisted and minimally invasive procedures.
• Vaccine therapy, using a patient’s own tumor cells to create a cancer-fighting vaccine.

“Our goal is to enhance the treatment options available to our patients,” said Lynn Schuchter, MD, chief of hematology-oncology at Penn. “We now have an unprecedented opportunity to combine chemotherapy with proton and other new, molecular-targeted therapies and exactly tailor the right treatment for every patient.”

Just like all tools, these treatments are only as good as the craftsmen using them. The members of the cancer teams at Penn are leaders in research and treatment. They are recognized for developing the best treatment plan for every patient and delivering optimal care through careful and thorough planning.

Physicians point out that while proton therapy is an exciting treatment option, it is not appropriate for all patients or all types of cancer. Dr. Hahn said Penn is taking a careful approach in determining when proton therapy is most appropriate and establishing protocols to ensure that those patients who can benefit most from the new therapy are seen quickly.

The Difference is the Beam
The physical characteristics of the proton beam differentiate it from other types of radiation therapy. The goal of all radiation therapy is to provide the maximum exposure needed to destroy cancer tissue while minimizing the effect on the surrounding, healthy tissue.

Traditional radiation therapy — often called photon therapy — delivers radiation from the point where it enters the body to where it exits. It is often delivered via multiple beam angles that intersect at the site of the tumor to provide maximum exposure to the cancer cells. It is a very effective tool in treating many types of cancer, especially in combination with surgery and chemotherapy.

Proton therapy uses powerful magnets to bend and control positive-charged protons in a circular path as they are accelerated to near light speed inside a cyclotron. The speed of the resulting beam, and therefore its energy, is measured in electron volts, and the higher the voltage, the deeper the beam penetrates in a patient’s body before releasing tumor-killing energy.

Proton particles are heavier and bigger than photons so they travel further before releasing their energy. The speed to which they are accelerated propels them directly to the tumor site where they release their energy. Exposure to the surrounding tissue is minimal, and the radiation does not travel beyond the targeted site.

Like all forms of radiation, proton therapy works by aiming the energized particles onto the target tumor. These particles damage the DNA of cells, ultimately causing their death. Because of their high rate of division, and their reduced ability to repair damaged DNA, cancerous cells are particularly vulnerable to this attack on their DNA.

Precise Treatment
The most effective use for proton therapy is treating tumors in areas where the surrounding organs or tissues are especially sensitive to radiation. Initial studies show it is best suited for the treatment of brain tumors, head and neck cancers, eye melanoma, tumors in and around the spine, cancers in the pelvic region and gastrointestinal tract, and possibly lung cancer. Sam Yoon, MD, surgical oncologist, has had success treating spinal, paraspinal, retroperitoneal, and liver tumors with surgery and proton therapy.

“The spinal cord and many abdominal organs such as the liver, kidney and bowel are very intolerant of radiation,” said Dr. Yoon, “so before or after surgically removing tumors near these structures, we use proton therapy to treat any residual disease in the surrounding tissues. Proton allows us to more reliably treat the area with a higher dose of radiation without harming these radiosensitive organs.”

A Unique Opportunity
Roberts Proton Therapy Center is the largest proton therapy facility in the world associated with an academic medical center and one of only seven such centers in the United States. Proton therapy is an FDA-approved treatment for cancer; however, because of the limited number of centers the research into the treatment and its effectiveness are also limited.

Research is a key component of Penn’s proton therapy program. Physicians have some idea of how certain tumors and sites react to proton therapy, but further research is needed to identify all of the indications for use and establish treatment protocols.

“We are opening clinical trials for proton therapy in every type of cancer,” said Dr. Hahn. “Several studies have already been approved and we have nearly 20 additional trials we are proposing. Penn will be a major contributor to research of proton therapy.”

When completed, the Roberts Center will have five treatment rooms, four gantries (90-ton rotational machines designed to deliver the therapeutic beam at the precise angle prescribed by the physician), and one fixed-beam room. It is projected that 3,000 patients will be treated each year, including several hundred children, through the continuing close relationship between Penn Medicine and The Children’s Hospital of Philadelphia. Penn has also established a new relationship with Walter Reed Army Medical Center, through which proton therapy technology will be available to treat United States military personnel and veterans.

For more information about the Roberts Proton Therapy Center at Penn, call 800-789-PENN (7366) or visit PennMedicine.org .

Combining Therapies for Better Outcomes

Radiation, chemotherapy and surgery are all effective in treating cancer. Ongoing research shows that combining these therapies can improve outcomes and prevent recurrence for many patients.

Radiation oncologists, cancer surgeons and medical oncologists from Penn Radiation Oncology and the Abramson Cancer Center at the University of Pennsylvania work closely with each other to develop the most effective treatment plan for every patient. Often, chemotherapy and radiation are administered together for better results or to increase the effectiveness of surgery.

Surgery and radiation are considered localized therapies. That is, they treat the tumor at its point of origin and prevent recurrence in that same location. Systemic treatments such as chemotherapy, endocrine therapy and molecular therapy are designed to kill any microscopic cells that have gotten into the bloodstream and traveled elsewhere in the body.

Challenges of Lung Cancer
One of the reasons that lung cancer is so deadly is because it is difficult to diagnose in its early stages, when treatment is most successful. There are usually no real symptoms of lung cancer until it is very advanced and has often spread beyond the lung.

“For advanced lung cancer that has not spread, chemotherapy and radiation given together is the definitive treatment,” said Alexander Lin, MD, a Penn radiation oncologist who specializes in treating lung and head and neck cancers.

Lung cancer presents many treatment challenges. Lung tissue itself is very sensitive to radiation, especially in long-term smokers with poor lung function. There are also vast differences in the tissue components of the chest — including bone, soft tissue and air — that radiation penetrates differently.

“We are continually looking for new ways to measure the radiation dose to the lungs,” Dr. Lin said. “We have to maintain a very fine balance between treating cancer and minimizing exposure of the surrounding tissue. Because of improvements in technology, we have found that we can escalate the radiation dose given for lung cancer in an accurate manner. ”

Numerous studies also suggest chemotherapy makes cancer cells more sensitive to radiation. The two therapies are often used concurrently to achieve the best results.

“Our goal is always to deliver the most effective treatment that maximizes radiation exposure to the tumor and minimizes toxicity to the surrounding tissue,” Dr. Lin said.

CT scans are also now being used to track the movement of the lungs and the cancer through the breathing cycle. Using the scans, radiation oncologists can more accurately target radiation exposure to the tumor while sparing normal tissue.

Penn physicians plan to use proton therapy with the goal of improving the efficacy of radiation therapy for lung cancer.

More Effective Treatment for Breast Cancer
Most patients with breast cancer are treated with surgery—either mastectomy for larger tumors or lumpectomy for smaller cancers—but chemotherapy and/or radiation are often incorporated into the treatment plan to reduce the chance of recurrence.

“Surgical treatment of breast cancer is very effective,” said Robert Prosnitz, MD, MPH, a Penn radiation oncologist who treats breast cancer patients. “But there is evidence to support the addition of radiation as a way to prevent recurrence. Large studies have consistently shown that radiation therapy can reduce the risk of cancer recurrence by about 50 percent in patients with ductal carcinoma in situ (a non-invasive cancer), and by about 75 percent in patients with invasive breast cancer.”

CT-guided therapy is also used in treating breast cancer, according to Dr. Prosnitz. CT scans give a three-dimensional picture of the patient’s anatomy and allows physicians to design radiation fields that treat the breast and, in some cases, the adjacent lymph node regions, while minimizing the radiation exposure to the underlying lung and heart. When planned with care, radiation therapy for breast cancer has very few short- or long-term side effects.

The Penn Difference
Experience is essential to developing treatment plans and accurately targeting radiation therapy. Many of Penn’s physicians, like Drs. Prosnitz and Lin, are subspecialists who only treat specific types of cancer.

Coordination of care is vital when combining therapies, according to both Drs. Lin and Prosnitz. Along with radiation oncologists, Penn’s treatment teams include surgeons, medical oncologists, pathologists and diagnostic radiologists. The team members meet regularly to discuss treatment plans and challenging cases.

“Our cancer programs are all located in the Perelman Center for Advanced Medicine. The fact that we are all in one location facilitates true multidisciplinary care. We are constantly talking to one another and this close communication is essential when patients are being cared for by multiple specialists at once,” Dr. Prosnitz said. “We can truly provide better coordinated, interdisciplinary care to all of our patients.”

Proton Therapy FAQs

James Metz, MD, associate professor and vice chair of the clinical division of Penn Radiation Oncology, answers some frequently asked questions about proton therapy.

Q: What is proton therapy?

A: Proton therapy is a kind of external beam radiation in which protons (hydrogen atoms from which the electrons have been

removed) are directed at a tumor. Proton therapy is effective because of its ability to accurately target and kill tumors, both near the surface and deep within the body, while minimizing damage to the surrounding tissues.

Q: How is proton radiation different from that produced by conventional radiation?

A: Protons exist in the nuclei of atoms and have electrons orbiting them, and thus have both a positive charge and a relatively large mass. In contrast, conventional or photon radiation lacks both charge and mass. These differences account for the distinct physical properties of the proton beam. X-rays are produced by linear accelerators that excite electrons; gamma rays originate with the decay of radioactive elements such as cobalt-60. Proton beam radiotherapy is generated by a hydrogen ion source and accelerated in a large machine called a cyclotron. (The cyclotron at the Roberts Proton Therapy Center weighs more than 200 tons.)

Q: How is proton therapy different from other forms of radiation therapy?

A: As a result of the differences in its electromagnetic characteristics, proton therapy offers potential advantages over conventional radiation therapies. Many of these advantages are derived from the ability of radiation oncologists to limit exposure to normal tissue with proton radiation.

X-rays and gamma rays gradually lose energy as they move through the body and the energy deposited tends to be greater at shallow depths and exponentially lower as the beams move through the body. Charged protons can be delivered at specific velocities with the greatest energy loss occurring just before the particle stops. Little or no energy extends beyond the target point. The concentrated energy is released at the tumor site so more energy reaches the cancerous cells, and more damage occurs with each burst of radiation. Side effects caused by the irradiation of normal tissue in front of and behind the tumor are not totally eliminated, but dramatically reduced.

Q: How does proton therapy work?

A: Proton therapy, like all forms of radiation therapy, works by aiming energized particles at a tumor. These particles damage the DNA of the targeted cells, ultimately causing their death. Because cancer cells have a high rate of division, and a reduced ability to repair damaged DNA, they are particularly vulnerable to radiation.

Q: What cancers can proton therapy be used to treat?

A: Proton beam radiation therapy is useful in treating a variety of cancers including:

• Brain and cranial base tumors.
• Tumors of the eye.
• Sarcomas.
• Prostate cancer.
• Spine tumors.
• Thoracic cancers.
• Gastrointestinal cancers.
• Pediatric cancers.
• Head and neck cancers.

Q: Why use protons?

A: The advantages of proton therapy include:

• Same tumor-killing properties as X-rays.
• Decreased dose to normal tissues by 50 to 70 percent.
• Decreased side-effects and complications.
• Decreased toxicity.
• Ability to treat tumors close to critical organs.
• Potential to increase radiation dose administered to the targeted tumor.
• Potential reduction in the number of daily patient treatments.
• Possibility of increased cure rates.
• Potential to re-treat tumors after recurrences.
• Added capacity to treat benign conditions.

Q: Who performs proton therapy?

A: Proton therapy is administered by a team of highly trained specialists including radiation oncologists, radiation physicists, dosimetrists and radiation therapists. A diagnostic radiologist may perform imaging studies to help design the treatment. In addition, radiation therapy nurses help patients in their daily treatments, including management of the side effects.

Q: What are the side effects of proton therapy?

A: It depends on the area of the body being treated. Typically, because much less normal tissue is affected, the side effects of proton therapy are less frequent and less intense than with conventional photon radiation.

Q: How is proton therapy integrated with other therapies (combination therapy)?

A: Proton therapy may be used in conjunction with other treatment modalities, including conventional radiation and chemotherapy. The combination of proton therapy and conventional radiation therapy permits an escalation of dose to the tumor, while minimizing radiation dose to normal tissues.

The combination of radiation therapy with chemotherapy can be difficult due to the side effects seen with some combinations, but protons may allow for the development of more effective and less toxic combination therapies. To improve patient outcomes, Penn hopes to combine chemotherapies with protons in ways that are not possible with conventional radiation.

Research Advances Treatments – Quality of Life

Penn’s ongoing research programs have advanced cancer diagnostics, developed radiation and surgical techniques and medications that improve patient outcomes. Combinations of those therapies are improving treatment effectiveness and enhancing results. Cancer care has evolved in many ways, and Penn is able to offer its patients more options for treatment.

Every day, Penn researchers look for the reasons why certain people and certain cancers respond differently to the same treatments.

“We follow our patients before, during and after their treatments, looking for the correlations between cancer therapies and clinical outcomes in an effort to provide customized medicine,” said John Plastaras, MD, PhD, of Penn Radiation Oncology. “We also ask our patients about their quality of life, assessing the impact of their underlying disease and cancer therapies on their symptoms and daily functioning.”

In addition to the current and planned clinical trials relating to proton therapy, Penn Radiation Oncology is currently enrolling patients in many clinical trials that will lead to improved diagnostic and treatment procedures, including:

Photodynamic Therapy
Photodynamic therapy administers a light-sensitive drug that is absorbed by tumor cells. The drug becomes active and kills cancer cells when it is exposed to light. The current trial studies the effectiveness of using photodynamic therapy during surgery to kill any remaining cancer cells for patients with involvement of the lining of the chest and lungs (pleura) by mesothelioma and lung cancer.

Nelfinavir
A protease inhibitor used to treat or prevent HIV infections, nelfinavir was originally part of the HIV triple drug cocktail. Non-toxic on its own, the drug makes cancer cells, but not normal cells, more sensitive to radiation. Trials are now open to test its effectiveness for treating lung cancer and glioblastoma multiforme (GBM).

Hypoxia
Many tumors live in a low-oxygen or “hypoxic” environment, which makes them more resistant to radiation and chemotherapy. Furthermore, hypoxic tumors are more likely to invade adjacent tissues and metastasize (spread) to distant body sites. Several studies are under way to test the agent known as EF5, developed at Penn, and its role in diagnosing the presence and pattern of hypoxia in tumors with positron emission tomography (PET) scans. By finding these hypoxic areas, Penn researchers hope to learn how to overcome this mechanism of cancer cell resistance to therapy.

Calypso^® 4D Localization System
Calypso is a data collection system that acts like a GPS for the body. Radiofrequency transponders are introduced to the cancer site, such as the prostate, allowing the movement of the tumor to be tracked on a screen. The state-of-the-art system ensures that the radiation is precisely delivered to the target, making the treatment both safer and more effective. Calypso has been approved for use in treating prostate cancer, and trials are under way at Penn to test the system’s effectiveness in other areas of the body.

Flaxseed
Some studies have shown that flaxseed helps protect normal tissue that may be especially sensitive to radiation, such as the lungs. When treating patients with lung cancer, radiation of the normal lung surrounding the tumor can lead to breathing problems. In this clinical trial, patients eat flaxseed muffins to help them better tolerate the treatment.

Tempol
Many patients receiving radiation for brain tumors experience hair loss during their treatment. In this clinical trial, patients use tempol, a topical hair gel that acts as a protectant, preventing hair loss.

For more information about cancer research at Penn, please call 800-789-PENN (7366) or visit PennMedicine.org.

Radiation Therapy Precisely Targets Cancer Cells

Radiation oncologists at Penn Medicine understand that every patient is different and every cancer is different. Because Penn has more treatment options than many other cancer centers, the radiation oncology team can develop customized treatment plans that are designed to target patients’ cancer cells.

“We want to better understand tumor biology so that we can improve targeting of therapy and deliver a more effective dose to the tumor while minimizing toxicity to normal cells,” said Ramesh Rengan, MD, PhD.

Radiation oncology works by focusing radiation directly on cancer cells, damaging their DNA and preventing them from replicating. When cells are unable to replicate, they die.

“Radiation creates reactive oxygen in cells that damages the DNA,” said Dr. Rengan. “Normal cells can repair that damage but for cancer cells it creates a time bomb that destroys the cell the next time it tries to divide.”

Dr. Rengan explained that radiation therapy is given as a series of doses over time. It allows the normal cells time to repair the damage from the radiation while building on the damage to the cancer cells.

Radiation therapy treatment plans are prepared using sophisticated, three-dimensional computerized imaging and treatment planning systems. Treatment options available for cancer patients at Penn include:

• Intensity-modulated radiation therapy (IMRT).
• Image-guided radiation therapy (IGRT).
• Brachytherapy.
• Gamma Knife^®.
• Mammosite^®.
• Respiratory gating.
• Photodynamic therapy.
• Positron emission therapy (PET).
• Conformal radiation therapy.
• Proton therapy.

While having the latest technology is important in radiation oncology, Dr. Rengan emphasizes the equipment is only as good as the physicians and the team who plan the therapy and deliver the treatment. A critical factor in the success of treatment is the experience of the team. The greatest chance for successful treatment comes from having an experienced team. In addition, many patients at Penn are on established protocols to study the benefits and side effects of their treatment. This helps the team continue to improve treatments and patient care.

For more information about radiation oncology, call 800-789-PENN (7366) or visit PennMedicine.org.