Case Review: A 61-Year-Old Woman With Metastatic Cholangiocarcinoma
Expert oncologist Milind Javle, MD, reviews the diagnosis and treatment of intrahepatic cholangiocarcinoma in a 61-year-old who presents with jaundice and changes in stool and urine color.
Transcript:
Milind Javle, MD: The patient being described here is a 61-year-old woman who was previously healthy other than a mild case of diabetes that is somewhat poorly controlled. She also has metabolic syndrome; she is overweight, and she’s working on that, as we all do. She presents with painless jaundice or alteration in liver function tests; she goes to her primary physician, has blood work, and it was noted there that the bilirubin and liver enzymes were elevated, suggesting that there is some degree of blockage of the biliary tree. This then led to further investigations, including a sonogram. It was thought to be gallstones, but then it turned out that she actually had a mass in the liver. There was a follow-up CT scan, which revealed a large central mass in the liver, along with some satellite...within the liver, as well as regional lymph nodes.
After all the results of these tests, she was diagnosed with cancer, although we were not quite sure what type of cancer. This was followed by a core needle biopsy of the liver, which revealed adenocarcinoma. It was clearly not liver cancer, or hepatocellular cancer [HCC], but it was adenocarcinoma. The possibilities here are a primary liver cancer, such as cholangiocarcinoma, not HCC, or it could be metastatic disease coming from other sources.
Since the diagnosis or site of the primary tumor was uncertain, there were further investigations that were initiated, including immunohistochemical analysis of the biopsy tissue. This revealed that the tumor was CK7-positive, CK20-negative, so clearly it was an adenocarcinoma. It was coming from perhaps an upper GI [gastrointestinal] source, or pancreatic, or a biliary source. There were further investigations, including: HepPAR [immunohistochemical stain] for HCC, which was negative, CDX2, which was negative. Other investigations included TTF1 for lung cancer and ER/PR [estrogen receptor/progesterone receptor] for breast cancer, all of which were negative. This was then a diagnosis of exclusion. The diagnosis that the pathologist suggested and that the clinician readily agreed to was intrahepatic cholangiocarcinoma, or a primary cancer involving the bile ducts within the liver.
The patient was started on systemic chemotherapy because clearly this mass was multifocal; it was involving vasculatures. It was not resectable, so she was started on systemic chemotherapy with gemcitabine and cisplatin given weekly on a 2 weeks on, 1 week off schedule per the ABC-02 trial. The patient tolerated this treatment well, and she received follow-up imaging every 2 months. She did relatively well for the first 4 months, and then a subsequent restaging scan showed that there was progressive disease in the liver as well as in the bones. This suggested that the tumor had become refractory to systemic chemotherapy.At this time, the patient had molecular profiling through next-generation sequencing using a core biopsy that was obtained from the tumor.
This patient was treated a couple of years ago when there was no approved therapy for this cancer in terms of targeted therapy. Molecular profiling in this case revealed a FGFR2-BICC1 gene fusion, which is one of the most common FGFR2 fusions seen in cholangiocarcinoma. She was enrolled in a clinical trial with infigratinib. This was a phase 2 trial that enrolled about 120 patients. This trial included patients with cholangiocarcinoma who had received prior systemic chemotherapy, either first line or subsequent line, and had to have adequate laboratories, renal, and hepatic function for enrollment. Patients were required to have measurable disease, and then received infigratinib in a dose of 125 mg daily on a 3 weeks on, 1 week off schedule. The duration of this therapy was until progression, and each cycle was defined as 4 weeks in duration. This patient was enrolled on this trial, and she tolerated the therapy. She received this therapy well; at the first restaging scan we noted that there was no more progression, there was stable disease. Many of the patient’s symptoms appeared to have improved as well; she continued on this therapy for a total of 6 months, experiencing stable disease as her best response.
Cholangiocarcinoma is thought to be a rare cancer, however, in fact, there are about 10,000 to 15,000 patients being diagnosed in the United States every year. This disease is more common in other parts of the world, such as in Asia. Unfortunately, the disease is rising in incidence, perhaps because of the epidemic of obesity, metabolic syndrome, and diabetes. In addition, there are other substance abuse causes, such as alcohol hepatitis. In this situation, because this was thought to be a cancer of unknown primary, it led to further investigations, such as immunohistochemical analysis. It’s quite typical that cholangiocarcinoma is in fact a diagnosis of exclusion. That is, you rule out other possibilities based on clinical grounds and sometimes with the need of endoscopy. In this case, an endoscopy was not performed because she really didn’t have any upper GI symptoms.
However, because she had jaundice, we did perform an ERCP [endoscopic retrograde cholangiopancreatography] and a stent placement in bile duct, in the common hepatic duct where the obstruction was. During that process, there was an endoscopy that showed no primary in the stomach. This is quite typical in this case to make this diagnosis by excluding other cancers. Also quite typical now, and it should be more so, is molecular profiling, that is obtain a tissue biopsy and send it for next-generation sequencing.
Transcript edited for clarity.
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Case: A 61-Year-Old Woman with Metastatic Cholangiocarcinoma
May 2019
Initial presentation
- A 61-year-old woman presents with jaundice and changes in stool and urine color.
Clinical workup
- Enlarged liver is palpable on physical examination
- Blood work reveals serum levels of CA 19-9 (1400 U/ml), bilirubin 2 mg/dL, ALT 550 U/L, AST 120U/L
- Patient undergoes CT imaging and is found to have multiple liver masses, consistent with metastatic disease or intrahepatic cholangiocarcinoma (iCCA)
- Histopathological examination identifies adenocarcinoma, CK7+, CK20-, HepPAR-, TTF- consistent with cholangiocarcinoma or upper GI Primary
- Patient is diabetic and somewhat non-compliant with her diabetes medication
- Her ECOG PS is 1
July 2019
Treatment
- Patient is treated with chemotherapy (gemcitabine + cisplatin) for 24 weeks.
- Patient is monitored for disease progression every 2-3 months by CT imaging.
July 2020
- Patient does well for 1 year after initiation of treatment but now has elevated CA 19-9 levels.
- MRI scans show several liver and bone lesions but no signs of brain metastases.
- Lab results are normal (absolute neutrophil count 4,000/mm3, platelets 150,000/ml, hemoglobin 12.1 g/dL
- Patient undergoes NGS testing (Foundation Medicine, Inc.) and is found to have FGFR2-BICC1 gene fusion
- Patient meets eligibility criteria for infigratinib phase 2 study and is enrolled in the trial and being treated with infigratinib
- Patient does not show any signs of disease progression on MRI scans for six months, suggestive of stable disease and CA19-9 levels stay within normal limits.
