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The Andrew L. Warshaw, MD, Institute for Pancreatic Cancer Research
Monday, July 16, 2012
Advances, Summer 2012
These treatment teams are making special progress in three disorders: pancreatic cancer, bile duct cancer, and pancreatic cysts (the evaluation and management thereof).
A Message of Hope in Pancreatic Cancer
While pancreatic cancer is relatively rare compared with cancers of the colon, lung, and breast, with about 44,000 new cases diagnosed each year in the U.S., it is largely an aggressive disease with a sobering prognosis. Nevertheless, the progress made in developing new treatments for pancreatic cancer is encouraging.
Patients seeking care at Mass General Hospital and the Digestive Healthcare Center benefit from treatment with the latest in radiation techniques, including newly developed proton beam therapy. Mass General is the only medical center in New England to offer this treatment for patients with resectable pancreatic cancer. Rather than having surgical resection immediately following diagnosis, patients are offered this new form of radiation therapy in combination with standard chemotherapy prior to surgery. The technique involves just a one-week course of radiation treatment compared with the standard five weeks of postsurgical radiation in traditional protocols.
This tumor is an incidentally discovered cyst in a young woman that turned out to be a mucinous cystic neoplasm, seen here in the pathology picture.
For pancreatic cancer, proton beam therapy has the advantages of convenience and less toxicity because the treatment is of shorter duration and focused to spare healthy tissue. Mass General physicians led the phase 1 safety and feasibility trial on the technique under the guidance of Theodore Hong, MD, director of gastrointestinal radiation oncology, and Carlos Fernandez-del Castillo, MD, director of the Pancreas and Biliary Surgery Program and clinical co-director of the GI Cancer Center. Results of the 15-patient trial were published in 2011 in the International Journal of Radiation Oncology. The protocol was shown to be reasonable and safe. Patients were given one of four radiation doses in progressively shortened schedules along with chemotherapy. Surgery followed within one to six weeks after completion of chemotherapy. No dose-limiting toxicities or unexpected postoperative complications were noted. A phase 2 study has just been completed, with results presented at the 2012 American Society of Clinical Oncology conference in Chicago. Dr. Hong and colleagues are investigating proton beam radiation as a platform to which other agents are added, including radiation modifiers that make cancer cells more susceptible to radiation. An example includes the drug hydroxychloroquine, an existing medication developed for malaria treatment. When cancer cells perceive external harm, such as with radiation, they can retreat into a dormant-like state without experiencing cell death. The cancer can resurface, however, and become resistant to treatment. Hydroxychloroquine inhibits this cell-preserving strategy. Mass General researchers have just begun combining it with proton beam radiation to treat patients with pancreatic cancer, with the hope of improving the sensitivity of radiation and accompanying chemotherapy.Mass General researchers are also investigating new radiation modifiers for treating patients with inoperable pancreatic cancer. Very early investigational studies have shown that some of these patients responded well following treatment with vorinostat, a drug used to treat T-cell lymphoma, in combination with radiation. For more than 20 years, Mass General has been a center of excellence in intraoperative photon beam radiation techniques for pancreatic cancer and other cancers, and it is the only site in New England offering intraoperative radiation for unresectable pancreatic tumors. New Endoscopy Era for Bile Duct Cancer
CT scan of a mucinous cystic neoplasm.
Less common than pancreatic cancer, bile duct cancer strikes about 2,000 to 3,000 people each year. New imaging technologies at Mass General are improving the accuracy of bile duct cancer diagnosis during endoscopy. With confocal laser endomicroscopy, an imaging catheter is placed into the bile duct, allowing the endoscopist to look at the cells in real time. If bile duct cancer is detected, treatment can involve surgery, chemotherapy, and/or radiation. Additionally, stenting may be used to aid in drainage of the bile duct while at the same time the patient receives palliative care. Although stenting does not remove the cancer, it often reduces excessive bile in the duct, consequently relieving discomfort and improving a patient’s quality of daily life. At Mass General, interventional endoscopists use stents in patients with bile duct cancer who cannot or should not have surgery. The procedure can be done in combination with chemotherapy and radiation.Covered Metal StentsOne of the most significant recent clinical advances in the palliative treatment of bile duct cancer has been the availability of high-quality, removable metal stents and the palliation they provide. Being able to place and remove stents is important because leaving them in long term poses a risk for infection and blockage. Without adequate drainage, bile duct tumors pose a serious risk of infection of the bile duct and the liver. Although patients receive antibiotic treatment, resistance develops over time, making it increasingly difficult to drain all the infected material as a result. Infection associated with bile duct cancer is the most common cause of death from the disease.Led by William R. Brugge, MD, director of GI endoscopy, Mass General physicians conducted a large prospective randomized clinical trial investigating new metal stents that are designed to provide long-term treatment to patients with bile duct cancer. These stents are now used routinely for palliative purposes at Mass General, permitting draining of the duct over the long term. Since many bile duct tumors are relatively slow growing, during a period of two to three years, stenting provides essential drainage, enabling patients to survive over this time with reduced symptoms and lessened complications.Radiofrequency Ablation
One of the most significant advances in active treatment for bile duct cancer is radiofrequency ablation (RFA). During RFA, the endoscopist places a heated catheter into the bile duct and burns off cells along the lining of the duct. Several patients have successfully been treated with RFA at Mass General. A pilot study of the procedure, which has institutional review board approval, is now in place at the hospital and is actively recruiting new patients.If clinical studies find that RFA is effective and safe, it could replace photodynamic therapy (PDT), a technique involving intravenous injection of a light-sensitive chemical into the bile duct. Once activated by light, the chemical ablates diseased tissue. But this approach leaves a patient’s skin very sensitive to light and is extremely expensive, because many treatments are usually required. With RFA, Dr. Brugge expects that once a patient receives a treatment, he or she will return in a few months for follow-up, at which time an additional treatment can be performed if remaining cancer is detected.RFA is most likely to be useful for patients with bile duct cancer who cannot have surgery or do not respond well to radiation or chemotherapy. It may also become a first step in treatment followed by radiation and chemotherapy as necessary.Evaluating Pancreatic Cysts
Magnetic resonance cholangio pancreatography (MRCP) of a side-branch intraductal papillary mucinous neoplasm (IPMN).
Endoscopic ultrasound guided fine needle aspiration (FNA) of a malignant pancreatic mass.
The increased use of better-quality imaging protocols has led to a rise in detection of pancreatic cysts. Although a proportion may become malignant, many pancreatic cysts do not require active treatment. Differentiating between low- and high-risk lesions is difficult with traditional imaging. Therefore, better methods are needed to evaluate these cysts to improve imaging and better aid treating physicians who are unsure how to properly diagnose a patient with a pancreatic cyst.Endoscopic ultrasound is routinely used to assess pancreatic cysts at Mass General. Though many treatment centers rely on tandem MRI and CT scans to evaluate these cysts, research conducted at Mass General shows that endoscopic ultrasound gives excellent information—not just about the size of the cyst but also about its relationship to the duct itself and to other structures within the pancreas. The ultrasound also provides data about the presence of nodules within the cyst and the thickness of the cyst wall. With endoscopic ultrasound fine needle aspiration (EUS-FNA), a technology developed at Mass General, endoscopists can not only visualize the cyst but also remove a sample of the cyst fluid and biopsy any solid cyst component. The fluid is sent to cytology and analyzed for various markers, such as elevated levels of carcinoembryonic antigen (CEA), which suggests the presence of malignancy, or for the presence of molecular changes, notably the KRAS genetic mutation.
Mass General physicians are also investigating the use of a new imaging technique called optical coherence tomography (OCT) to photograph and evaluate pancreatic cysts. In a pilot study of tissue removed during pancreatectomy, researchers, including Dr. Brugge, showed that OCT can help distinguish low-risk pancreatic cysts from higher-risk cysts. A new in vivo study is about to begin at the hospital to evaluate the potential of OCT imaging in combination with EUS-FNA for differentiating between cystic lesions of the pancreas.Should surgical excision be necessary, Mass General surgeons can offer patients a less invasive procedure—a laparoscopic distal pancreatectomy to remove cysts in the pancreatic tail. This option provides for a quicker recovery than a standard open operation. Patients with cysts in the middle of the pancreas may benefit from a middle pancreatectomy, an operation pioneered at Mass General. This procedure avoids the removal of excess healthy tissue and surrounding organs, which is a common consequence with the larger Whipple surgery, a standard surgery for removing pancreatic tumors.Mass General Hospital’s Digestive Healthcare Center is at the forefront of new treatments for a variety of pancreatic and biliary disorders. Some of the newest procedures have been developed through the hospital’s network of experienced clinicians, who work in a multidisciplinary setting. This means that patients newly diagnosed with a pancreatic cyst benefit from tools that better distinguish between benign and cancerous tumors. And patients with pancreatic or bile duct cancer can be assured of receiving the best endoscopic, radiological, and surgical treatments available, even for cases previously considered terminal. callout Selected References
Massachusetts General Hospital Digestive Healthcare CenterThe Massachusetts General Hospital Digestive Healthcare Center is a collaborative practice of gastroenterologists, endoscopists, surgeons, radiologists, pathologists, hepatologists, oncologists, and radiation oncologists dedicated to the prevention, diagnosis, treatment, and management of digestive diseases. The Digestive Healthcare Center offers a full range of medical and surgical treatments for digestive diseases, including conditions of the esophagus, stomach, small and large intestines, liver, gallbladder, pancreas, and colon.Pancreas and Biliary Center: 55 Fruit Street, Blake 4, Boston, MA 02114. Access line: 1-877-644-3636 | Patient line: 617-643-5677 massgeneral.org/CISTThe Digestive Healthcare Center is organized into six disease areas dedicated to the diagnosis and management of digestive health issues. For more information about these services, visit massgeneral.org/digestive
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