NEW YORK—Oncologists are driving the field of personalized medicine as they become more aware that they can get tissue core biopsies of such malignancies as pancreatic cancer, according to a speaker here at the Chemotherapy Foundation Symposium here.
“'Tissue is still the issue' in pancreatic cancer,” said James Farrell, MD, Director of the Center for Pancreatic Diseases at Yale University School of Medicine. “It's important that every pancreatic disease patient have a tissue diagnosis derived through endoscopy since a small percentage of patients have benign disease. Even more of an issue is to use the biopsied tissue to develop biomarkers. We hope to move past diagnosis toward a personalized treatment for pancreatic cancer.”
The role of endoscopy in the management of pancreatic cancer is in evolution, he continued. New uses of endoscopy, in addition to tissue core biopsy, include early diagnosis and high-risk screening, staging after treatment “downstaging,” a changing role for preoperative stenting, metal biliary stenting in the neoadjuvant/downstaging setting, and endoscopic ultrasound (EUS)-guided treatment.
Pancreatic cancer has one of the worst prognoses of all solid tumors, with the high mortality rate (about 95 percent) due, in part, to the majority of patients (about 80 percent) presenting at an advanced stage. Patients with metastatic disease have a median survival of only two to six months, the one-year survival rate is about 15 to 20 percent, and less than three percent of patients survive to five years, he said.
Endoscopic imaging has an established role in pancreatic cancer in early disease. “Technological advances now allow us to obtain tissue for histological purposes through core biopsy. This has changed the perception of how to deal with patients and how to diagnose pancreatic cancer,” Farrell said.
“As oncologists become aware of the availability of tissue core biopsies, they will put pressure on their colleagues to do more biopsies and to get more predictive markers, not only for pancreatic cancer but for all malignancies.”
Although the vast majority of patients with pancreatic disease have cancer, a small percentage—about five percent—have chronic pancreatitis—“a benign disease that mimics pancreatic cancer,” he noted. “We have the ability to confirm this diagnosis right away. We should not treat patients without a tissue diagnosis.”
Early diagnosis and screening for pancreatic cancer are essential, Farrell said. Practicing oncologists are not necessarily involved in early detection, but “they deal with pancreatic cancer patients who have a high incidence of familial cancer. Practicing oncologists should ask their patients about any family history of pancreatic cancer to identify patients who can enter into a screening program.”
A family history of pancreatic cancer is defined as having:
* Two or more first-degree relatives with primary-site pancreatic cancer, or one first-degree relative who also has at least two second-degree relatives affected with pancreatic cancer;
* A known gene mutation, with family history of pancreatic cancer, such as the BRCA2 gene mutation or the FAMM/p16 gene mutation;
* Familial breast-ovarian cancer with one affected first-degree or second-degree relative with pancreatic cancer; or
* Peutz-Jeghers Syndrome.
New biliary-stent technology is now available for use in the preoperative and neoadjuvant/downstaging settings, Farrell said. There are two types of biliary stents—plastic and metal. “Plastic stents are less expensive and smaller, but occlude more frequently. Metal stents are larger and last longer, but are more expensive.”
Patients with operable disease and biliary duct obstruction should not have a biliary stent. “For patients with borderline resectable pancreatic cancer who are undergoing prolonged neoadjuvant therapy, I prefer metal stents,” he said. “This allows the patient to get through several series of chemotherapy.”
The stents can be uncovered, partially covered, or fully covered. “Patients who have inoperable pancreatic cancer should have a partially covered or fully covered stent,” Farrell said, adding that if the opportunity arises, he recommends inserting a metal stent.
Modern treatments of pancreatic cancer include EUS-guided therapies, stereotactic radiation therapy, and palliative therapy, he said.
Although a high dose of radiation can be delivered precisely to the pancreas using stereotactic radiation therapy, researchers must validate what is happening in patients with real data. More evidence is necessary to determine which therapeutic approaches are the best and safest for pancreatic cancer patients, he said.
For palliative therapy of duodenal obstruction, endoscopic treatment is superior to surgery and provides better symptom relief, along with shorter hospital stays and at lower costs.
“Oncologists need to co-manage pancreatic cancer patients with their gastrointestinal colleagues, not only for early diagnosis of disease but also to create a treatment plan for advanced disease. This may include palliation to optimize the patient's and family members' overall quality of life,” he said.
Summing up, Farrell said, “With better diagnoses of pancreatic cancer, we can identify high-risk groups and apply imaging studies at the appropriate time to pick up precancerous disease. In that way we can personalize medical care by better understanding the different molecular settings. If we develop pretreatment assays, then we can tailor treatment to the individual pancreatic cancer patient.”
In an interview, the moderator of the session at which Farrell spoke, Jordan Berlin, MD, Clinical Director of the GI Oncology Program and Associate Professor of Medicine at Vanderbilt University Medical Center, said, “Pancreatic cancer diagnoses will improve if we can get SPARC [secreted protein acidic and rich in cysteine] data about the gemcitabine-plus-nap-paclitaxel [Abraxane]. If the data in Phase III trials, which should be available in 2014, match what we see in Phase I and II trials, this would help guide therapy.”
Gemcitabine plus nab-paclitaxel has been shown to be an active regimen in patients with advanced pancreatic cancer, and SPARC in the stroma, but not in the tumor, has been correlated with increased survival in the initial phase studies, he explained. “In the future, the SPARC data may tell us for which patients it would be biologically better to use gemcitabine plus Abraxane.”
However, he added, “I'm not a big believer in cytopathology because it has its weaknesses. Only a small number of cells are used in making the diagnosis. We don't often have the ability to do all the stains to differentiate neuroendocrine tumors from adenocarcinoma.”
Berlin said he does believe that the future will include better diagnosis of pancreatic cancer. “We will have personalized medicine when we can guide the right therapy, based on pathology. This is still a few years away, but tissue core biopsy is in the future. How predictive it will be still needs to be defined.”