Treatment of pancreatic cancer metastasized to the liver – A case study

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In the fall of 2015, 44-year-old Doron Broman was diagnosed with pancreatic cancer -and was surprised to find that his pancreatic cancer had metastasized to a large tumor on the liver. Faced with a survival period of only a few months, Broman decided to spend limited time in the right place.

 

Broman was diagnosed with metastatic pancreatic cancer at the age of 44

He is a Miami-based real estate developer and his home is in Boston. After conducting research online, he decided to receive treatment at Dana-Farber. His doctor Kimmie Ng, MD, MPH, director of clinical research at the Gastrointestinal Cancer Treatment Center, recommends the FOLFIRINOX regimen, which is the strongest combination chemotherapy for pancreatic cancer. Pancreatic cancer is the most infamous treatment.

Broman flew from Miami to Boston every two weeks for treatment. To everyone’s surprise, the malignancies of his pancreas and liver began to shrink rapidly.

“This is the most significant response,” Ng sighed. “Several tumors almost completely disappeared after chemotherapy. This makes us wonder if there is a molecular mutation in his tumor that makes it particularly sensitive to FOLFIRINOX.”

Oncologists began to look for unusual molecular changes or mutations in the coding of tumor DNA, because they saw a patient significantly improve cancer drugs, and the drug usually has a moderate response or no benefit to other patients with the disease. These types of patients are called “special responders.” In the era of precision medicine, sequencing DNA from cancers of special responders may identify rare mutations, making patients ’tumors extremely sensitive to specific drugs.

Broman’s cancer responded immensely to the treatment recommended by Kimmie Ng, MD.

Broman happened to arrive at Dana-Farber treatment just after Ng and her colleagues just started a new research protocol, allowing patients to perform additional biopsies to obtain genetic material that can be treated with precision medicine. Broman agreed. The entire exon sequence of his tumor DNA revealed mutations in the BRCA2 gene. When this mutation is inherited by women, it will greatly increase the risk of breast and ovarian cancer. But Broman did not inherit the BRCA2 mutation -it was just that at some point in his life, his pancreatic cells randomly had this mutation.

BRCA2 mutations can interfere with a cell’s ability to repair DNA damage, causing the cell to destroy itself. Cancer cells with BRCA2 mutations are particularly sensitive to platinum-based chemotherapeutic drugs based on DNA damage, which is part of the FOLFIRINOX protocol. This may explain why Broman ’s cancer has been hit so successfully.

After 13 cycles of treatment with FOLFIRINOX, Broman responded well to the treatment with side effects such as hair loss and nerve damage, so his medical team decided to convert it into a targeted drug called olaparib called PARP inhibitor (Lynparza) can hinder DNA damage repair.

“Olaparib is approved for hereditary BRCA-2 mutation-related ovarian cancer,” Ng said. “However, in somatic [non-hereditary] BRCA2-mutated tumors, there is no real data on its role.”

Therefore, Broman stopped FOLFIRINOX and now takes 12 olabally daily. He said that there will be no side effects. Six months after his new protocol, MRI and CT scans showed no cancer recurrence, and pancreatic cancer blood biomarker levels remained within normal limits. Ng said his plan is to keep him taking olabally indefinitely, as long as it keeps the cancer under control and has few side effects.

Broman said: “I am really happy”. He has prayed every day since he diagnosed himself. He recently traveled to Europe and Israel where he was born. “I’ve done much better than I expected. I feel good, my hair is back, I’m healthy, I walk 12 miles a day, a Saturday and a day. My friends said they couldn’t believe it.”

For Ng and her colleagues, she said that Broman ’s case “points out that precision oncology and targeted therapy based on its molecular characteristics benefit cancer patients greatly.”

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