Advancements in Pancreatic Cancer Treatments

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The Whipple Procedure and Other Pancreas Surgeries:

At the time of diagnosis, pancreatic cancer is often found to have already metastasized (spread to other organs) and these patients will not benefit from surgical removal of their primary tumor.  Surgery can be performed as a potentially curative measure if the cancer is contained within the pancreas and has not spread to blood vessels, lymph nodes or other organs. This treatment option should be discussed with your physician to see if it is a viable option.

The type of operation performed for removal of pancreatic cancer is based on the location of the tumor.  For tumors of the head and neck of the pancreas a Whipple procedure, (also called a pancreaticoduodenectomy) is performed.  This is a complex operation perfected at Johns Hopkins.  Tumors that grow in the body and tail of the pancreas are removed  through a surgery known as a distal pancreatectomy.

Johns Hopkins performs more pancreas cancer surgeries than any other institution in the country. Each year, our surgeons perform more than 250 Whipple procedures and 100 distal pancreatectomies. Our team of experienced surgeons also includes the most experienced nurses and experts in gastroenterology, cancer genetics, and social work to provide the best and most complete care to our patients.

The Whipple Procedure
Until recently, pancreatic surgery was associated with a very high risk of surgically related mortality. Johns Hopkins Medicine surgeon honed the Whipple procedure to the point where the mortality rate now stands at 2 percent, when performed by experienced surgeons. Dr. Cameron has performed more than 2,000 of these surgeries — more than anyone else in the world. He has trained a team of pancreatic surgeons at Johns Hopkins Medicine to carry on his legacy.
During the Whipple procedure, surgeons remove the head of the pancreas, most of the duodenum (a part of the small intestine), a portion of the bile duct, the gallbladder, and associated lymph nodes. In some cases, the entire duodenum and a portion of the stomach must be removed. The surgery takes on average six hours to complete. Most patients stay in the hospital for one to two weeks following the Whipple procedure.

Chemotherapy
Chemotherapy involves the use of medications to kill cancer cells. The medications may be given intravenously or by mouth. These drugs are usually given in cycles, with alternating periods of treatment and recovery, and may be given alone or in conjunction with radiation therapy or surgery. The medications are very powerful and can lead to a wide range of side effects, including hair loss, changes in appetite, and fatigue.

Medical oncologist Daniel Laheru:
The leading chemotherapy agent is a drug called gemcitabine or Gemzar. Recent studies of gemcitabine combined with a drug called taxol, also known as Abraxane, conducted at Johns Hopkins and elsewhere, have shown increases in survival of more than 10 months, compared to giving gemcitabine alone.

Long used for metastatic breast cancer patients, taxol is a chemotherapy drug encapsulated in tiny shells made to target cancer cells. Additional studies are planned to include a larger number of patients with multiple institutions participating.
Researchers at Johns Hopkins are working to develop new agents for the treatment of pancreas cancer. Ongoing clinical trials at the Johns Hopkins Kimmel Cancer Center are available for patients who have not yet received any treatment, or, for those whose tumor is not responding to standard treatments.

Radiation Therapy
Dr. Joseph Herman, Radiation Oncologist and Multidisciplinary Clinic Director at the Pancreatic Cancer Center.
One-on-One with Joseph Herman, M.D. radiation oncologist and Pancreas Multidisciplinary Cancer Clinic director
There have been vast improvements in the delivery of radiation therapy for cancer patients over the past 10 years, explains Joseph Herman, M.D.

 More from Dr. Herman on Johns Hopkins team of experts.
We now have very focused radiation therapy to treat the primary tumor, while limiting radiation exposure to normal, adjacent tissue, he notes. The machines we use today employ multiple beams of radiation, directed at different angles to different parts of the body.
Modern radiation techniques allow for movement in the abdomen while a patient breathes, Herman says, and can better target the tumors during that motion.
Contrary to some patients’ beliefs or fears, he adds, radiation therapy is unlikely to burn the skin, to leave red marks, or cause skin toxicity.
And, similar to an X-ray, the treatment does not cause pain when administered and will not leave patients radioactive.
Standard, conventional radiation therapy is delivered Monday through Friday, once a day, over a five- to six-week period. The treatment takes approximately 15-20 minutes, or up to an hour. Most patients receiving radiation therapy are given chemotherapy in the same time frame.

In some cases, Dr. Herman and colleagues offer palliative radiation therapy. This treatment is typically given over a two-week period and is used to relieve pain for patients or slow local tumor growth.
New therapies can be driven as much by marketing as medical results, and it is important for consumers to be able to distinguish which one is in play when they are making treatment decisions. Radiation oncologist Joseph Herman says this is particularly true in his field, which delivers treatment through technologically advanced pieces of equipment. “Often claims are made about the usefulness of new techniques in the absence of information to support them,” says Herman.

Radiation therapy services, offered through the Department of Radiation Oncology, provides a wide variety of pancreative cancer therapies and expert consultation.
Stereotactic body radiation therapy (SBRT)
Stereotactic body radiation therapy (SBRT) is a form of focused radiation used successfully to treat brain and lung cancers. CyberKnife, a type of stereotactic body radiation therapy, uses a robotic arm to deliver radiation in a number of different ways and at and at different angles.

More recently focused radiation has been touted as a promising new treatment for pancreas cancer, causing confusion among patients and concern among physicians. Why the concern? Herman says currently there is little evidence to show that stereotactic radiotherapy can shrink pancreas tumors or improve survival. “We need to gather evidence to scientifically determine which approaches are the best and safest for patients,” says Herman. “We must validate what we say or believe is happening in patients with real data.”

Pancreatic Cancer Vaccine
The Johns Hopkins Kimmel Cancer Center in Baltimore has always been focused on translational research—laboratory discoveries that improve the lives of patients. One of their many successes has been a pancreas cancer vaccine. The vaccine was developed more than decade ago in the laboratory by scientist and pancreas cancer program director Elizabeth Jaffee, M.D., a leading cancer immunology and pancreas cancer expert, and taken to patients by leading pancreas cancer clinician Daniel Laheru, M.D.  Jaffee and Laheru are co-directors of the Skip Viragh Center for Pancreas Cancer Clinical Research and patient Care.
To make vaccine therapy a reality, Jaffee became an expert in U.S. Food and Drug Administration regulations and vaccine manufacturing, and opened a GMP (good manufacturing practices) facility at the cancer center to make the vaccine.

How the Pancreatic Cancer Vaccine Works
This novel vaccine, being tested in clinical trials, supercharges the immune system and causes immune cells, which tend to be tolerant of the cancer, to seek out and kill pancreas cancer cells throughout the body. It uses irradiated pancreas cancer cells that are incapable of growing, and have been genetically altered to secrete a molecule called GM-CSF. This molecule acts as a lure to attract immune system cells to the site of the tumor vaccine, where they encounter proteins called antigens on the surface of the irradiated cells. Then, these newly armed immune cells patrol the rest of the patient’s body to destroy any remaining, circulating pancreas cancer cells.
“Pancreas cancer is notorious for being in areas outside of the pancreas, and the vaccine allows us to get ahead of the disease and get microscopic cancer cells that escape other therapies,” says Laheru.
Pancreas cancer remains one of the most aggressive cancers with few treatment options making a real difference in long-term survival; as a result, Jaffee’s vaccine has attracted worldwide attention.

A Popular and Unique Potential Therapy
Clinic coordinator Barbara Biedrzycki, Ph.D., C.R.N.P., receives more than 60 inquiries a month from patients hoping to receive the pancreas cancer vaccine. After an appearance by Jaffee on the Dr. Oz television show, the clinic was flooded with more than 1,000 inquiries from patients all over the country.
“There is no other cancer center doing this kind of work,” says Lei Zheng, M.D., who is working with Jaffee on the pancreas cancer vaccine. The Skip Viragh Center has allowed Jaffee, Laheru and team to make these groundbreaking treatment advances available to patients throughout the U.S. and around the world.
Zheng is among the group of bright, young scientists supported through Skip Viragh’s legacy, and he is working with Jaffee in the laboratory to optimize the effects of her pioneering pancreas cancer vaccine. This support has been key to her research and was instrumental in her studies to decipher precisely how pancreas cancer and the immune system work together to allow the disease to progress.

Additional Vaccine Research
Activating the immune system to recognize pancreas cancer cells and simultaneously suppress mechanisms co-opted by tumor cells to shut down an immune response is a complex and delicate process. Jaffee and team have studied timing of vaccination as well as combining the vaccine with drug and radiation therapies to boost its tumor-killing capabilities. More recently, with the help of Viragh Scholar Dung Le, M.D., Jaffee has developed an approach that combines the vaccine with a drug treatment that targets mesothelin, a protein on the surface of pancreas tumor cells believed to contribute to the growth and spread of the cancer.
In other attempts to boost the effectiveness of the pancreas cancer vaccine, Zheng is focusing on connective tissue cells called stromal cells in the pancreas, and developing methods to attract cancer-fighting immune cells into tumors while suppressing and bypassing barriers that prevent them from attacking cancer cells.

He is among the first to recognize that stromal cells actively drive the growth and spread of pancreas cancer cells. In this brand new area of research, he is just beginning to decipher the molecular and cellular mechanisms they use.
Stromal cells are not prevalent in the normal pancreas, but in cancer, Zheng suspects that stromal cells become engaged as a result of inflammation or some other injury to the pancreas.

This injury may be an early event in cancer development attracting stromal cells as well as immune cells to the organ. Cancer cells somehow take advantage of the changes by creating a protective environment that allows them to grow. He hopes his novel research will lead to ways to target and inhibit these changes and create an environment less hospitable to cancer.

Other new work includes the use of peptides to create the first vaccines individualized to the unique molecular characteristics of each patient’s cancer and, as a result, improve the response against pancreas cancer. Peptides are the building blocks of proteins and are a “table of contents” of sorts displayed on the cell surface to reflect the internal molecular structure of the cell.

Vaccines could use peptides to prime immune cells to recognize when something is not right within a cell, such as with cancer. Researchers are studying whether identifying peptides that mark each patient’s specific tumor cells, incorporating these peptides in the pancreas cancer vaccine, and then combining them with immune-modulating drugs that release cancer’s grip on immune cells, could boost the immune response against cancer cells.
Jaffee’s ultimate goal is to use these discoveries to develop a vaccine that prevents pancreas cancer.  She and her team are focused on deciphering the specific information the immune system needs to immediately recognize early changes in cells that occur before cancer develops.

Palliative Care
Like many pancreas cancer patients, former patient and donor Skip Viragh experienced significant pain.  Pancreas cancer causes pain because the pancreas is located near several critical organs that are impacted as the cancer grows and spreads. In addition, the pancreas is part of the digestive system and it is where insulin is manufactured, so patients often require nutritional and dietary support.
“Our mission is to fully take care of patients, and that means not only treating their cancer but the symptoms and side effects it causes as well,” says Thomas J. Smith, M.D., the Harry J. Duffey Family Professor of Palliative Medicine at Johns Hopkins in Baltimore and one of the world’s leading experts in palliative care.
Smith works with Johns Hopkins Kimmel Cancer Center clinicians to help guide the management of cancer-related symptoms, including physical signs such as pain and nutritional issues common to pancreas cancer, but also anxiety, depression, and essentially anything that affects patients’ quality of life.  Smith and team meet with patients to discuss and understand their goals.

http://www.hopkinsmedicine.org/kimmel_cancer_center/centers/pancreatic_cancer/treatments/