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Warning Signs of Pancreatic Cancer and Advances in Treatment

By Cheryl Platzman Weinstock, February 2022


Abdominal Survival rates have risen and there are new treatments, but early diagnosis is key.


Twenty years ago, getting a pancreatic cancer diagnosis was very often devastating. The cancer usually wasn’t caught until later stages, partly because the pancreas is tucked behind the stomach, making it hard to detect tumors. Plus, some of the warning signs — abdominal discomfort, back pain, unintended weight loss and fatigue — are easy to overlook or attribute to other conditions. And they often arise late in the game.


The five-year survival rate for this kind of cancer was around 4 percent. For treatment, doctors were able to offer patients only standard chemotherapy, radiation and/or a risky surgery.

Today, however, the five-year survival rate for pancreatic cancer has more than doubled. If the disease is caught early and the tumor is small and confined to the pancreas, the survival rate is around 40 percent.


A surge in research funding is partly responsible for this good news. For example, at the National Cancer Institute (NCI), money for pancreatic cancer research rose from $17 million in 1999 to more than $182 million in 2018. Funding by other agencies and organizations has made similar leaps.

With stronger support, pancreatic cancer research is making huge advances. Scientists are developing new ways to screen for this cancer so that it can be caught earlier. Medical experts are also engineering new drugs to treat the cancer and finding innovative ways to repurpose existing therapies and deliver more focused radiation to tumors to shrink them, which can make removing them easier.


Shubham Pant, M.D., associate professor in the Department of Gastrointestinal Medical Oncology at the MD Anderson Cancer Center in Houston, is hopeful that some of these breakthrough treatments will help to “double the rate of survival in the next five years.”

Here are a few of the latest treatments and advances.

The great promise of targeted therapy

Up to 25 percent of pancreatic cancer patients have unique molecular alterations in their tumors. Now researchers can study these differences using technologies such as molecular profiling, which allows doctors to target treatments individually.


A large study published in 2020 in The Lancet Oncology found that pancreatic cancer patients who received tailored drug therapy based on their tumor’s unique characteristics lived an average of one year longer than those who did not receive targeted therapy.

In 2018, a year after being diagnosed with pancreatic cancer, Karen Kiernan, 63, a retired nurse from Naperville, Illinois, received such a targeted therapy with Keytruda, a drug approved for treating lung and other cancers. By then Kiernan had severe back pain from her cancer and had lost 40 pounds. But once she began taking Keytruda, she was able to regain some weight and return to doing the things she did before she had cancer. Her recovery hasn’t been without the occasional bump, but Kiernan says she is “truly in remission now.” “I think we are starting to see more progress and traction in testing every pancreatic cancer patient’s tumor,” says Michael Pishvaian, M.D., director of the Gastrointestinal, Developmental Therapeutics and Clinical Research Programs at the Johns Hopkins Kimmel Cancer Center. He estimates that more than half of all pancreatic cancer patients are now having their tumors tested.

“This is definitely something patients can take some measure of control over. They should generally feel more comfortable and be more aggressive in asking their doctor for this,” Pishvaian says.

Using the breast cancer drug Lynparza

Mary Phillips, 59, was diagnosed with metastatic pancreatic cancer in March 2016. At first she took the latest combination chemotherapy for pancreatic cancer. Then she enrolled in a clinical trial of the drug Lynparza. Because the medication was already being used by some patients with breast or ovarian cancer (those with a mutation in their BRCA or DNA repairing genes), researchers thought that it could be useful for pancreatic cancer patients with the same mutations.

Early findings in this area have been promising. A 2019 study, published in The New England Journal of Medicine, reported that patients with such a BRCA mutation who took Lynparza for metastatic pancreatic cancer had no new tumor growth, and no spread of their cancer, for twice as many months as those not receiving the drug. Still, there was no difference in long-term survival past 18 months. In December 2019, the Food and Drug Administration approved the medication for maintenance therapy for this group of patients.

Phillips has some advice for others after her experience with the disease: “Do everything you can and know that you tried everything. … You got to stay alive until the next best thing comes along.”

Delivering more with guided radiation therapy

Norman Kravetz, 71, of Boynton Beach, Florida, was diagnosed with stage 3 pancreatic cancer in 2019. He had six months of intensive chemotherapy, followed by cutting-edge MRI-guided radiation therapy at the Dana-Farber/Brigham and Women’s Cancer Center in Boston. The new technology combines two ways of targeting the tumor to increase precision.


Without MRI guidance, radiation therapy can be technically challenging because of the location of the pancreas in the middle of the abdomen. “MRI guidance allows us to visualize and accurately deliver radiation treatment in order to treat the tumor with high doses of radiation while reducing the radiation dose to nearby vital structures, thereby reducing the risk of side effects,” explains Joseph Mancias, M.D., Kravetz’s radiation oncologist.

After the six months of chemo and just one week of the new radiation treatment (usually available at major medical centers across the country), Kravetz saw his tumor shrink, and in early 2020, he was able to have surgery to remove it.

“Everything is back to normal. I go to the gym five to six times a week. … I am healthy and feel great,” Kravetz says. “[The doctors] call me the miracle guy.”

Using artificial intelligence to read scans

Early pancreatic cancer can be subtle enough that it’s missed on scans 30 percent of the time, which means that about half of all cases aren’t caught until later stages, as was true with Jeopardy! host Alex Trebek, who died of the disease in November 2020.


“We should be able to do better,” says Elliot Fishman, M.D., professor of radiology and radiological science at the Johns Hopkins School of Medicine in Baltimore. To that end, Fishman is in his fifth year of using artificial intelligence to teach the computer to read CT scans to detect tumors at earlier stages so they can be surgically removed.

So far Fishman has screened several thousand pancreatic cancer patients with the technology and has been able to detect tumors with 90 percent accuracy.

Using blood and urine screenings to detect cancer early

As is done for many other cancers, a simple blood or urine test may one day be used to screen for pancreatic cancer in its earliest stages, since body fluids contain bits of DNA from tumor cells. Research teams are developing methods of blood-based DNA analysis to detect pancreatic cancer with high accuracy, says Brian Wolpin, M.D., associate professor of medicine at Harvard Medical School and director of the Gastrointestinal Cancer Center at Dana-Farber.

“Scientists have made quite a bit of progress in the last five years in developing these multi-cancer early detection tests, and large studies are now ongoing to define their utility,” says Wolpin, who notes that such procedures may be able to detect cancerous tissue 90 percent of the time. Meanwhile, in clinical trials in the United Kingdom and Finland, researchers are studying urine analysis to detect pancreatic cancer this way.


Early Warning Signs of Pancreatic Cancer


If your pancreatic cancer is caught at an early stage, you have a higher chance of a cure and can better tolerate treatment, says Brian Wolpin, M.D., of the Dana-Farber Cancer Institute. That’s why you should watch out for the following symptoms.

Abdominal and back pain


The most common symptom of pancreatic cancer is abdominal discomfort in the mid to upper abdomen, above the belly button, that often radiates to the back. This kind of pain can also be experienced by people with ulcers and gallstones, or even reflux. The typical pain associated with pancreatic cancer, however, can be very dull at first but can become very severe and persistent, explains James Farrell, M.D., director of the Yale Center for Pancreatic Diseases at the Yale Cancer Center.


Diabetes with weight loss


Another sign is new onset diabetes or worsening of blood sugar levels, especially paired with unexplained weight loss, says Wolpin, senior author of a study on the topic published in JAMA Oncology in 2020.


He and his research team found that recent onset diabetes was associated with a threefold higher risk of pancreatic cancer. The incidence rates for this type of cancer were six- to tenfold higher among study participants with newly diagnosed diabetes and weight loss than among participants without diabetes or weight loss.

Researchers are continuing to study the potential impact diabetes has on pancreatic cancer risk. An ongoing study is currently looking at whether a blood test can identify diabetics and prediabetics who may need further testing for pancreatic cancer.


Darkening of urine and lightening of stool; jaundice; itching


Sometimes pancreatic cancer can obstruct the duct that contains bile, a fluid secreted by the liver that aids in the absorption of nutrients. When the duct gets blocked, it can cause a backup of bile that may get into the bloodstream, causing jaundice (yellowing of the skin and eyes), darkening of the urine, lightening of the stool and, less commonly, itching.


Nausea and vomiting


It can be hard to tell whether these symptoms are indications of pancreatic cancer or the result of something like food poisoning or a new medication. “If the symptoms are new, don’t resolve after 24 hours and result in excess dehydration, or if they progress, medical attention should be sought,” Farrell advises.


Fatigue


People with this cancer are often lethargic. “It’s not the kind of severe fatigue you get with the flu,” Wolpin observes. Instead, you become less active and feel like you can’t do as much as you used to, and you’re more tired at the end of the day.


Loss of appetite and unintentional weight loss


Often patients with pancreatic cancer start eating less, in part because they don’t feel well. They can also feel bloated or fuller sooner after eating. Take note if these symptoms seem to get worse over time, Wolpin says.


Know — and Lower — Your Risk Factors for Pancreatic Cancer


“Increasing awareness of the risk factors associated with pancreatic cancer development — such as having a family history of pancreatic cancer, having a pancreas cyst on a CT or MRI scan, or developing new onset diabetes — offers the opportunity for us to diagnose pancreatic cancer early and intervene, with the overall hope of improving patient outcome overall,” says James Farrell of the Yale Center for Pancreatic Diseases at the Yale Cancer Center.

You can lower your risk for pancreatic cancer by changing unhealthy lifestyle behaviors you can control, such as smoking, drinking and being overweight.


About 25 percent of pancreatic cancers are thought to be caused by cigarette smoking. Cigar smoking and using smokeless tobacco raise your risk, too, according to the American Cancer Society (ACS).


People who are obese (BMI of 30 or higher) are about 20 percent more likely to develop pancreatic cancer, according to the ACS. Type 2 diabetes is more common among overweight adults, and this condition raises the risk for pancreatic cancer, too, especially in those over 50 who suddenly develop type 2 without having a family history of it, says Brian Wolpin, M.D., of the Dana-Farber Cancer Institute.


Drinking alcohol can lead to chronic pancreatitis, or inflammation of the pancreas, which has been linked to an increase in pancreatic cancer.


Certain risk factors for pancreatic cancer can’t be changed, but they’re important to know, and you should share yours with your doctor.


About 10 percent of pancreatic cancers are thought to be the result of genetics. If you have a family history of the disease, talk with your doctor about whether you should be screened for it.


A family history of other cancers and syndromes can also raise your risk for pancreatic cancer. These include hereditary breast and ovarian cancer caused by BRCA1 or BRCA2 mutations, and Lynch syndrome, an inherited disorder associated with colon cancer.


Data has been mixed about whether long-term use of proton pump inhibitors to reduce stomach acid, or infection with Helicobacter pylori (a bacteria that can cause ulcers), increases the risk of pancreatic cancer, Wolpin says.


Other risk factors include age, gender and race. Men develop pancreatic cancer slightly more often than women. The risk of developing it increases with age. African Americans are more likely to get pancreatic cancer than any other racial group.


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