On a Monday in early 2012, Cathie Lusby went to see her general practitioner about a troublesome and persistent illness playing havoc with her digestive tract.
By Friday, at the end of a head-spinning week of lab tests and scans, she was meeting an oncologist at MD Anderson’s Katy location and confronting one of the most difficult diagnoses: pancreatic cancer.
Remembering the shock of the week and her early encounters at MD Anderson, Lusby recalls how nurses, staff and oncologist Nikesh Jasani, M.D., associate professor of General Oncology, made her feel welcomed and reassured.
“Nobody ever promised, ‘You’re going to be cured.’ But they said, ‘We’ll do our best and get you as far through this as possible.’
“I’m cancer-free, five years as of July 5,” Lusby says.
Moon Shot builds on progress
Nationally, only about 9% of people diagnosed with pancreatic cancer survive five years. In most cases, the disease has spread to other organs by the time it’s discovered.
Surgery is the standard of care when the tumor is surgically removable, but even then the median survival for such patients is about 22 months.
At MD Anderson, it’s 43 months, the result of a shift toward routine presurgical treatment and steady improvements in imaging, surgery, radiation, chemotherapy and other specialties built through multidisciplinary teamwork in research and clinical trials over the past 25 years. Now, MD Anderson’s Pancreatic Cancer Moon Shot™ adds analytical capabilities.
How to make surgery more successful
Less toxic chemotherapy combinations and targeted radiation before surgery can improve the prospects of patients whose tumors might once have gone to surgery first, says Robert Wolff, M.D., professor of Gastrointestinal Medical Oncology, also a Moon Shot co-leader and Sheikh Zayed Bin Sultan Al Nahyan Distinguished University Chair in Medical Oncology.
Safer and more effective surgical techniques as well as improvements in care right before, during and after surgery have been critical in improving survival.
“Our mortality within 90 days of surgery is essentially 0% of patients, and our length of hospital stay after surgery is six days,” Katz notes.
Nationally, the surgery-related death rate is about 8%, and the post-surgical hospital stay is over 10 days.
Presurgical treatment also is used to shrink more locally advanced tumors to make them removable, Wolff says. Careful assessment helps ensure the disease has not spread to other organs, because surgery is futile then.
Taking time to prepare and recover
Lusby’s tumor was locally advanced, with nearby lymph nodes affected but no organs beyond her pancreas, Katz says.
So she began a five-drug chemotherapy infusion called FOLFIRINOX every two weeks for four sessions, followed by 10 sessions of targeted radiation and oral chemotherapy. Next came PET and CT scans to make sure the cancer had not spread.
The scans yielded other excellent news.
“Dr. Katz was very happy with how much the tumor had shrunk,” Lusby recalls.
But that didn’t mean she was ready for the operating room. It’s important for patients to have some recovery time from earlier treatment and to get in better shape for the rigors of surgery and recovery, Katz says. His team conducts studies of exercise programs tailored for patients.
Lusby took six weeks off treatment before surgery, working out at the gym and spending lots of time on her bicycle, building up to 10-mile round trips.
Full recovery after surgery took months, Lusby says. It included another four rounds of FOLFIRINOX and a feeding tube inserted below her stomach to allow that organ to recover faster.
She and her husband Randy began to walk at Katy Mills Mall.
“It’s 0.85 mile around the mall, and I remember walking it the first time with my feeding tube and my chemo pump, making it halfway around once,” she recalls.
But they persisted, and now the habit remains, five laps around the mall, five days a week.
What works and why just for some
Understanding why patients like Lusby do well and why treatment is less effective for others is central to improving results for patients with non-metastatic disease.
Deep molecular analysis of blood and tumor samples will help the team address these issues.
“We aim to bring novel clinical trials to these patients and conduct correlative studies to understand factors involved in response to, or resistance to, treatment,” says Anirban Maitra, M.B.B.S., professor of Pathology, co-leader of the Moon Shot and director of the Sheikh Ahmed Center for Pancreatic Cancer Research.
Through the Moon Shot, MD Anderson experts also are using an abbreviated radiation treatment for the pancreas known as stereotactic body radiation therapy (SBRT). SBRT has a similar or sometimes better effect than conventional radiation but is administered over five days instead of six weeks, allowing for shorter stays for MD Anderson’s out-of-town patients. The therapy delivers high doses of radiation, using several beams of varying intensities aimed at different angles to precisely target the tumor.
This precise targeting of the tumor has less effect on surrounding organs, so there’s limited toxicity. Conventional radiation requires concurrent chemotherapy and can lead to more toxicity because it usually includes a larger volume of radiation over time. SBRT uses a smaller, more focused volume and therefore can be easier on patients’ immune systems.
Cullen Taniguchi, M.D., Ph.D., assistant professor of Radiation Oncology, is working on a clinical trial that tests the use of higher doses of SBRT along with a drug designed to protect the small intestine from the effects of radiation.
Adding treatment of earlier stage, surgically removable disease takes advantage of the superior approach developed at MD Anderson and seeks to extend it with greater efficiency to more patients.
“MD Anderson leads in treatment of these patients, but we can and must do even better,” says Maitra.
Pancreatic Cancer Moon Shot
The Pancreatic Cancer Moon Shot™ is one of 13 cancer Moon Shots seeking to reduce deaths from cancer by accelerating development of new treatments, early detection and prevention methods based on scientific discoveries.
In addition to the initiative to target surgically removable, early- and middle-stage tumors of the pancreas before the disease has spread to other organs, the Moon Shot focuses on:
Development of blood tests to identify pancreatic cancer before symptoms are noticed is proceeding to larger validation studies to advance earlier findings.
Maitra and Sam Hanash, M.D., leader of the Moon Shots Program™ proteomics platform, lead this effort to assemble a panel of blood-borne molecules and proteins that act as a “liquid biopsy” and identify the disease. They’ve found several blood markers with predictive power, but are searching for more to complete the test, which will take several years to validate.
Even with a liquid biopsy, an important next step would be successful imaging of the pancreas to confirm disease. Work is underway with Eugene Koay, M.D., Ph.D., assistant professor of Radiation Oncology, to hone imaging algorithms that can pick out lesions in the pancreas that might be missed with the traditional visual analysis of CT scans and MRIs, including cysts that are likely precursors of cancer.
A high-risk clinic has been established to more closely monitor people who have a family history of the disease or genetic mutations that raise the risk of developing pancreatic cancer. Florencia McAllister, M.D., assistant professor of Clinical Cancer Prevention, leads the new clinic. Pancreatic cancer risk is higher in those whose parents, siblings or children developed the disease, particularly at a young age, and in those who have any of 10 genetic mutations, including a mutation in the BRCA2 gene, which is better known for raising the risk of breast cancer.
Pancreatic cancer that has spread to other organs is swiftly lethal. The Pancreatic Cancer Moon Shot seeks to bring new targeted therapies and immunotherapies to clinical trials for those with metastatic disease. Working with MD Anderson’s Institute for Applied Cancer Science, new therapies that target tumor metabolism and genetic regulation are in the preclinical pipeline. Immunotherapy projects are developing new ways to deploy T cells, the targeted troops of the immune system, against the disease.