Tom Dinwiddie kept busy in between treatments. He replaced the roof on his house and installed a new washer and dryer in his utility room. “
Patient With Rare Pancreas Cancer Beats The Odds
Published
From the Duke Cancer Institute archives. Content may be out of date.
Tom Dinwiddie, 69, was featured in the Journal of Gastrointestinal Cancer four years ago for having survived 30 months past an end-stage cancer diagnosis. He’s now lived nearly six years with no evidence of recurrent or metastatic disease.
Just after Thanksgiving last year, he made a special trip to Duke Cancer Center to share his story, explaining that it was his “moral obligation” to get the word out.
“In 10 months, I went from incurable to cured,” Dinwiddie said. “I've come back every year since. I’m not giving up these appointments.”
It was on April 2, 2012, that Dinwiddie’s local gastroenterologist in High Point, NC diagnosed him with metastatic stage 4 poorly differentiated neuroendocrine carcinoma of the pancreas. A CT scan revealed a 5-centimeter mass in the head of his pancreas and multiple tumors in his liver. A biopsy confirmed it was cancer.
His gastroenterologist said nothing could be done and he only had a couple months to live.
“When you hear the words it’s like getting hit upside the head with a brick,” said Dinwiddie, his voice trembling. “I cried myself to sleep.”
The next morning Dinwiddie told his wife Diane that he wasn’t going to “lay here and wait to die.”
“I was fighting mad,” recalled Dinwiddie. “I called the doctor back and said, “Look, if this was five years from now there would probably be a cure. Can you help me find a doctor who can keep me alive for five years? That’s my goal.”
He was offered referrals to MD Anderson, The Moffitt Center and Duke Cancer Institute. Duke Cancer Institute stepped up to take on Dinwiddie’s case.
Fighting Another Day
Six weeks after the initial CT scan, a staging PET-CT scan showed rapid growth of the tumor in his pancreas to 6.4 centimeters and a near doubling of his largest liver lesion to 6.3 centimeters. It didn’t look good.
Dinwiddie’s cancer had a Ki67 index of 90 percent. (The Ki67 index measures what percentage of cells are growing/dividing; 100 percent being the maximum.)
“His disease was doubling in size every four weeks; which is incredibly fast,” explained his DCI oncologist. “These tumors have a very poor prognosis, and likely would have taken his life in less than three months without treatment.”
A Hail Mary Pass
Dinwiddie’s case was run by the tumor board. The consensus was that cure was not an option, and that the focus should be on managing symptoms.
Dinwiddie pushed back. He said he’d only accept “aggressive curative care.”
“I was going to do any damn thing in my power to win; if you’ve had a good life you’ll do anything to have another day,” said Dinwiddie. “I really turned a corner when my doctor agreed to help me. We were a team.”
The standard regimen for metastatic poorly differentiated neuroendocrine cancer of the pancreas, which originates in the endocrine cells that make hormones to control blood sugar, is a combination of the chemotherapy drugs cisplatin and etoposide. However, this recommendation, his doctor explained, is "based on established practice patterns with very little evidence.”
So, the tumor board recommended something different — dose-modified FOLFIRINOX administered on days one and 15 of each 28-day cycle. FOLFIRINOX is a combination of 5-fluorouracil (5FU), oxaliplatin (which is similar tocisplatin), and irinotecan.
That specific aggressive drug combination is frequently used to treat a more common type of pancreatic cancer (adenocarcinoma, which forms in the exocrine cells that produce enzymes to support digestion) — not standard for his kind of cancer — but it had been shown to kill cancer when cells are dividing. Dinwiddie’s cancer cells were in a state of near constant division.
“They called it a Hail Mary pass,” said Dinwiddie.
Touchdown
Within a week, the swelling (edema) in his legs and feet went down and his energy level improved.
After two months, CT scans revealed a partial response to treatment. The mass in his pancreas was reduced more than 70 percent, and all measurable liver lesions were also smaller.
Over the course of the next eight months, Dinwiddie received FOLFIRINOX, which he tolerated well. Then he had another CT. His primary pancreatic mass had shrunk to 1.4 centimeters and his multiple liver metastases had each decreased to under a centimeter.
On January 23, 2013, Dinwiddie underwent a pylorus preserving pancreaticoduodenectomy — also known as the Whipple procedure — as well as a right hepatectomy (the removal of the cancerous portion of the liver) at Wake Forest Baptist Cancer Center.
He recovered quickly, walking 50 laps around the halls of the ward soon after surgery.
“On January 24, I declared myself cured,” said Dinwiddie.
Pathology following surgery showed that he’d had a near-complete response to the FOLFIRINOX. There was a 2-millimeter focus of residual cancer cells in the removed pancreas tissue and rare microscopic foci of metastatic disease within the removed liver tissue. The margins were negative and there were no lymph node metastases.
Dinwiddie’s case and the other case reported in the Journal of Gastrointestinal Cancer were the first reported cases of patients with high-grade or poorly differentiated pancreatic neuroendocrine carcinoma treated with first-line FOLFIRINOX. His DCI care team said Dinwiddie "achieved near-complete pathological response and currently has no evidence of measurable disease nearly seven years since his initial diagnosis, far exceeding historical norms." "Unfortunately, it isn't feasible to conduct a large randomized clinical trial of FOLFIRINOX for this “extremely rare patient population.” That's because these patients represent only around six percent of the 55,000 individuals diagnosed annually with pancreas cancer.
Tom Dinwiddie and his wife Diane relax with their rescue pets at their home in Linwood, NC — a wide spot in the road between Lexington and Salisbury. Dinwiddie designed and built the house in 1985.
Reassurance
Dinwiddie counts himself as fortunate to have survived a cancer that took the lives, most famously, of Steve Jobs and Aretha Franklin.
Once he was a survivor, he started volunteering with Pancreatic Cancer Action network (PANCAN) as a voice of reassurance to the newly diagnosed.
“When they’re first diagnosed, patients want to talk to someone who’s been there; they have no hope because that’s the way everybody is diagnosed,” he said. “Pancreatic cancer is a b**ch, but once in a while someone like me lives, and that’s a breakthrough.”
Today, Dinwiddie said, it’s as if he was never sick, except for the Creon pills he has to take with each meal. (They act as a substitute for the digestive enzymes that what’s-left-of-his-pancreas doesn’t produce). He’s still able to enjoy his favorite meal of pinto beans, greens and cornbread.
Surviving cancer didn’t change how he lives day-to-day.
The auto business retiree said he just wants “more of the same,” which includes fixing friends’ vintage Mercedes vehicles gratis and making home improvements.
A Reminder
Tom Dinwiddie has been keeping his chemotherapy port I.D. card in his wallet for nearly seven years. It reminds him of all he's been through.
Dinwiddie pulls out the chemotherapy port I.D. card he still carries in his wallet as a reminder of what he went through. He points out the date — May 16, 2012 — when his port was put in and his first chemotherapy treatment was administered. The port’s been out since 2013.
He gives thanks to science for his good health.
“Science is important to everyone here at Duke Cancer Center,” said Dinwiddie. “I stumbled on an answer for what was said to be incurable, right in my own backyard."
Learn More
According to NCI, the prognosis and treatment options for pancreas neuroendocrine carcinoma (PNETs) depend on whether the cancer has spread beyond the pancreas, whether the patient has MEN1 syndrome, the patient’s age and general health, and whether the cancer is newly diagnosed or has recurred.
A new Duke-led research study reveals groundbreaking insights into the mechanisms behind immunotherapy resistance in melanoma and colon cancer. Nicholas DeVito, MD, a Duke Cancer Institute medical oncologist specializing in gastrointestinal cancer, helped lead the research team in this work.The findings published in Cancer Research focus on the variability in patient responses to immunotherapy and the role of epithelial-mesenchymal transition (EMT) in this process. Despite the benefits of immunotherapy for approximately half of melanoma patients, the underlying mechanisms of resistance remain unclear."Not all patients with melanoma respond to immunotherapy, even though about half of them benefit from it, and most patients with colon cancer do not have a response at all” DeVito said. “Because of that, there's a question of, what is the mechanism behind that?"The team focused this research on the Hedgehog pathway, particularly the transcription factor GLI2, which they found plays a crucial role in immunotherapy resistance. The Hedgehog pathway, typically active during embryonic development, was shown to be associated with invasive and EMT in melanoma.The research revealed that GLI2 regulates two immunosuppressive pathways: the Wnt pathway and the prostaglandin pathway. These pathways are meant to help wounds heal, but tumors use GLI2 to activate pathways that have an immune suppressive influence on the microenvironmentUsing mouse models and patient samples, the team demonstrated that activation of GLI2 in cancer cells leads to immunotherapy resistance. They employed various techniques, including flow cytometry, single cell RNA sequencing, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to uncover the role of GLI2 in regulating immunosuppressive pathways.These findings suggest that inhibiting specific prostaglandin receptors can prevent immunotherapy escape, and blocking Wnt secretion can restore tumor control after immunotherapy escape, offering potential therapeutic strategies for patients.“If you had a high GLI2 signature in a tumor, there was a more than 75 percent chance that the patient is not going to respond to immunotherapy,” DeVito said. “The drugs that we've used in our mouse studies are all ones that have been used in humans, so they could be easily paired with a GLI2-based biomarker in clinical trials.”By identifying patients with high GLI2 signatures, clinicians can tailor treatments to improve outcomes. This approach is particularly relevant for colon cancer patients, who often exhibit primary resistance to immunotherapy.DeVito hopes to explore the role of GLI2 in colon cancer, particularly in patients with liver metastasis, and further develop biomarkers for combination treatments in this disease. His team is investigating how GLI2-mediated pathways contribute to immunotherapy resistance and spread to the liver by generating an immune-suppressive microenvironment, or ‘home’ for cancer outside the colon. The team is acquiring patient specimens and working with Jatin Roper, MD, assistant professor of medicine in the Duke Department of Medicine, to implement an advanced colon cancer mouse model that better represents human disease.“Immunotherapy is more tolerable and works better and longer than chemotherapy does,” DeVito said. “Using biomarkers, we can have an idea what the molecular pathways driving the immune landscape in the tumor are and can target those pathways in specific patients to improve the effectiveness of existing immunotherapies. Developing the ability to identify which immunosuppressive pathways are active in one tumor and not another also helps us not expose patients without those biomarkers to unnecessary treatments.”
A new Duke-led research study reveals groundbreaking insights into the mechanisms behind immunotherapy resistance in melanoma and colon cancer. Nicholas DeVito, MD, a Duke Cancer Institute medical oncologist specializing in gastrointestinal cancer, helped lead the research team in this work.The findings published in Cancer Research focus on the variability in patient responses to immunotherapy and the role of epithelial-mesenchymal transition (EMT) in this process. Despite the benefits of immunotherapy for approximately half of melanoma patients, the underlying mechanisms of resistance remain unclear."Not all patients with melanoma respond to immunotherapy, even though about half of them benefit from it, and most patients with colon cancer do not have a response at all” DeVito said. “Because of that, there's a question of, what is the mechanism behind that?"The team focused this research on the Hedgehog pathway, particularly the transcription factor GLI2, which they found plays a crucial role in immunotherapy resistance. The Hedgehog pathway, typically active during embryonic development, was shown to be associated with invasive and EMT in melanoma.The research revealed that GLI2 regulates two immunosuppressive pathways: the Wnt pathway and the prostaglandin pathway. These pathways are meant to help wounds heal, but tumors use GLI2 to activate pathways that have an immune suppressive influence on the microenvironmentUsing mouse models and patient samples, the team demonstrated that activation of GLI2 in cancer cells leads to immunotherapy resistance. They employed various techniques, including flow cytometry, single cell RNA sequencing, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to uncover the role of GLI2 in regulating immunosuppressive pathways.These findings suggest that inhibiting specific prostaglandin receptors can prevent immunotherapy escape, and blocking Wnt secretion can restore tumor control after immunotherapy escape, offering potential therapeutic strategies for patients.“If you had a high GLI2 signature in a tumor, there was a more than 75 percent chance that the patient is not going to respond to immunotherapy,” DeVito said. “The drugs that we've used in our mouse studies are all ones that have been used in humans, so they could be easily paired with a GLI2-based biomarker in clinical trials.”By identifying patients with high GLI2 signatures, clinicians can tailor treatments to improve outcomes. This approach is particularly relevant for colon cancer patients, who often exhibit primary resistance to immunotherapy.DeVito hopes to explore the role of GLI2 in colon cancer, particularly in patients with liver metastasis, and further develop biomarkers for combination treatments in this disease. His team is investigating how GLI2-mediated pathways contribute to immunotherapy resistance and spread to the liver by generating an immune-suppressive microenvironment, or ‘home’ for cancer outside the colon. The team is acquiring patient specimens and working with Jatin Roper, MD, assistant professor of medicine in the Duke Department of Medicine, to implement an advanced colon cancer mouse model that better represents human disease.“Immunotherapy is more tolerable and works better and longer than chemotherapy does,” DeVito said. “Using biomarkers, we can have an idea what the molecular pathways driving the immune landscape in the tumor are and can target those pathways in specific patients to improve the effectiveness of existing immunotherapies. Developing the ability to identify which immunosuppressive pathways are active in one tumor and not another also helps us not expose patients without those biomarkers to unnecessary treatments.”