Over the past 10 years, numerous clinical trials have been conducted to determine the best course of treatment for upper gastrointestinal (GI) cancers, which include gastroesophageal, pancreatic, small bowel, and neuroendocrine cancers. The results have been conflicting, raising questions about how to make treatment decisions and whether radiation and chemotherapy are more effective before or after surgery, or at both junctures.1
The Extended Education Session “Management of Complex Upper Gastrointestinal Cases: Implementation of Best Evidence,” to be held on June 2, will address these and other questions facing oncologists specializing in upper GI cancers.* The session will shed light on the latest research and its implications for establishing best practices in the field.
A Perspective on Treating Localized Pancreatic Cancer
John Ng, MD, of Weill Cornell Medical College, will open the session with a discussion of the role of radiotherapy in pancreatic cancer and how to use traditional and new forms of radiation to treat refractory and localized disease.
“Radiotherapy has been a standard component of pancreatic cancer treatment for decades,” Dr. Ng said. “Older trials indicated that radiation therapy provided a survival benefit, while others showed otherwise. The overriding issue facing oncologists around the world is how resistant pancreatic cancer is to all treatments and how to best take advantage of the newer options available to us.”
Dr. Ng said that radiation is an important tool in the treatment of localized pancreatic cancer. Used after combination chemotherapy, radiation can tip the balance so that the tumor becomes either resectable or more likely to result in a negative margin excision.
“A growing body of research is pointing to using radiation to shrink the size of tumors, making surgery possible or more likely to be successful,” Dr. Ng said. “The momentum is toward delivering chemotherapy and radiation in the neoadjuvant setting.”
Although the median overall survival for localized pancreatic cancer is poor, ranging from 12 to 30 months, a small number of patients with pancreatic cancer will live beyond 5 years.
“Patients diagnosed with pancreatic cancer know that the odds for long-term survival are against them,” Dr. Ng said. “As physicians, we want to be partners with our patients in striving to beat these odds. Chemotherapy and radiation used before surgery appear to be the best strategy for getting to that goal.”
Dr. E. Gabriela Chiorean
A Different Take on Localized Pancreatic Cancer
E. Gabriela Chiorean, MD, of the University of Washington, will be focusing on another aspect of the treatment conundrum: the lack of strong evidence for using radiotherapy in localized inoperable pancreatic cancer. The findings from the LAP07 randomized clinical trial illustrate the difficulty in solidifying the research base.
The study compared median survival among patients with locally advanced pancreatic cancer who received single-agent chemotherapy alone compared to those who received chemotherapy followed by radiation. The results showed little difference in median survival between the two groups (16.5 months vs. 15.2 months), although patients who received radiation had decreased local progression and fewer side effects.2 At this point, no other randomized clinical trial is studying the role of radiation for localized inoperable pancreatic cancer in the United States, although a few are currently underway in Europe.
“We are now in an era where we have more effective multi-agent chemotherapy platforms for pancreatic cancer,” Dr. Chiorean said. “And because we all know that this cancer is mostly a systemic disease, the decision of whether to include radiation following chemotherapy rests largely with individual oncologists.”
According to Dr. Chiorean, radiation may stabilize the disease so that it stays localized for a longer period of time for those patients whose disease remains inoperable after induction chemotherapy. It also can make the tumor resectable, resulting in longer survival for some patients.
That said, Dr. Chiorean is interested in building the research base in whatever way possible. “This is a topic with no clear answers,” she said. “I hope investigators from medical centers will come to the session and, after hearing our thoughts, consider sharing their data with us. The more clues we have about who will benefit from radiation, the more effectively we can treat our patients.”
Changing Landscape for Treatment of Liver Neuroendocrine Tumors
Dr. Emily K. Bergsland
But treatment plans must be individualized, integrating extent and pace of disease, primary tumor site, patient symptoms, and prior therapy. With new therapies on the horizon, therapeutic decision making is increasingly complex.
“Some patients do very well for extended periods of time on active surveillance alone or under treatment with a somatostatin analog (SSA), such as octreotide or lanreotide,” Dr. Bergsland said. “The optimal time to initiate SSA therapy—either upfront or at the time of progression—in otherwise asymptomatic patients is the subject of debate. Monthly SSA injections have been shown be beneficial, stabilizing tumor growth and reducing hormone secretion in patients with functional tumors.”
Other treatment options include liver-directed therapy (e.g., resection, ablation, or embolization), targeted agents (e.g., sunitinib or everolimus), and chemotherapy, but each strategy has its risks and benefits. Chemotherapy is used in selective cases when shrinkage is needed, typically in bulky, symptomatic pancreatic NETs and/or when other treatments have failed. Liver metastases can often be surgically debulked, but resection is not curative; the recurrence rate approaches 100% at 10 years.3 The goal of this strategy is to “set the clock back,” rather than to cure.
Everolimus, a targeted therapy that inhibits mTOR signaling, was approved by the U.S. Food and Drug Administration (FDA) in 2016 for nonfunctional, well-differentiated NETs of the GI tract and lung. Previously, only approved in pancreatic NETs, everolimus has been shown to stabilize progressing tumors.
Peptide receptor radionuclide therapy (PRRT) is a novel treatment approach that exploits the fact that well-differentiated NETs are characterized by somatostatin receptor expression. In a phase III clinical trial, treatment with a PRRT agent, Lu-177 DOTATATE, significantly delayed tumor progression in advanced mid-gut NETs compared to high-dose SSA therapy.4 FDA approval of this agent is pending.
“The field is changing rapidly,” Dr. Bergsland said. “It is important to decide on treatment approaches collaboratively with each patient, with careful consideration of the sequence of therapy. Weighing symptom control and reduction in tumor growth with quality of life should be part of the conversation.”
Speaker Riad Salem, MD, of the Feinberg School of Medicine, Northwestern University, will then focus on another treatment option for NETs: radioembolization. This approach involves inserting radioactive beads directly into the tumor to slow its growth.
Dr. Salem will be discussing RETNET (Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver), an ongoing phase III randomized multicenter trial, which is comparing progression-free survival following bland embolization, lipiodol chemo-embolization, and drug-eluting bead chemoembolization of neuroendocrine liver metastases (NCT02724540).
Dr. Prateek Sharma
Approaches to Treating Esophageal Cancer
Prateek Sharma, MD, of the University of Kansas Medical Center, will turn the discussion to esophageal cancer, which has a survival rate of only 15% to 20%.5 In addition, the rates of esophageal cancer are rising, probably due to a variety of environmental factors such as changes in diet, with increases in fatty foods; an increase in obesity; and a decrease of Helicobacter pylori infections in the stomach, which has a protective effect on the esophagus.
Dr. Sharma’s work focuses on Barrett esophagus, a premalignant lesion associated with esophageal and gastroesophageal cancer. He is studying the role of surveillance with an endoscope as a strategy for early detection of cancer.
“Although there is not clear evidence that surveillance reduces mortality from esophageal cancer, most guidelines recommend detailed inspection and biopsies for patients with Barrett esophagus,” Dr. Sharma said. “The regimen can be modified based on the degree of dysplasia, the patient’s age, coexisting conditions, and life expectancy.”
Manish A. Shah, MD, of New York-Presbyterian Hospital and the session’s chair, will address the use of PET scans to detect responsiveness to chemotherapy before surgery in esophageal cancer. He will discuss a clinical trial in its early stages that is focusing on how to treat patients, identified through PET scans, whose disease is likely to respond poorly to chemotherapy. Patients with poor responses, determined through PET scans, will be randomly selected into two groups: those who receive chemotherapy followed by surgery and those who go to surgery first, followed by chemoradiation. The results may have the potential to improve treatment options for a hard-to-treat group of patients.6
A common theme runs through all six panels: how to make the best use of new therapies and technologies to provide the best possible treatment for patients with upper GI cancers.
“We are all struggling to integrate new therapies into our practice,” Dr. Bergsland said. “This is a good time to be having the conversation about how to interpret the new research and optimize treatment for our patients.”
*Program information updated as of March 21. For session time and location information, please refer to the ASCO iPlanner on the Attendee Resource Center.