Impact of Family History on mCRC Diagnosis

Tanios Bekaii-Saab, MD, FACP:So, this is a 62-year-old female who just recently had the symptoms that were concerning, and that eventually led to a workup, a colonoscopy, showing ascending colons on the right-side mass that proved to be allRASwild-type andBRAFwild-type on biopsy. It’s adenocarcinoma that’sRAS/RAFwild-type.

Unfortunately, during the working up, the patient was found to have metastatic disease to the liver. There were concerns about lymph nodes that were enlarged and perhaps other areas as well—primarily liver, both sides. So, the patient eventually was referred to the medical oncologist who started her on FOLFOX and bevacizumab. She had a tough time with the chemotherapy and significant mucositis and diarrhea. The thought was it’s likely or primarily related to the 5-FU, so the bolus 5-FU was dropped, and then the regimen itself was dose reduced by about 50%. She did well after that; no further problems and had significant shrinkage of her tumors.

Following 4 months of chemotherapy with a great response, the decision was to move her from FOLFOX/bevacizumab to maintenance: low dose, continuous capecitabine/bevacizumab, which she tolerated very well and her disease remained very stable.

It’s always very important to consider the family history of cancer overall, but with a colon cancer patient specifically, there are other cancers that may be linked. The fact that her mother was in her 70s when she was diagnosed, and she’s in her 60s, makes this less likely to be an inherited cancer, in the absence of any other family members with colon cancer or other related cancers. So, the clear answer is probably not at this stage. Although, again, we screen everyone from microsatellite instability, which could point us into the most common aspect of inherited colon cancer and Lynch syndrome, and this patient’s microsatellite was stable.

Transcript edited for clarity.

November 2015

• A 62-year-old Caucasian female presents with severe crampy right lower quadrant pain
  • 6-month history of occult bleeding and weight loss of 15 pounds in the last 8 months
• PMHx: tonsillectomy at age 23; hysterectomy at age 55
• FHx: Mother diagnosed with colon cancer at age 71
• Laboratory findings: remarkable for Hb, 7.6 g/dL; CEA 5.5 ng/mL
• Colonoscopy reveals a large mass in the ascending colon, measuring approximately 11 cm
• Biopsy results: Invasive, poorly differentiated adenocarcinoma
• Additional pathologic testing
  • KRAS,NRAS, andBRAFwild-type
  • Microsatellite stable
• CT scan revealed widespread lesions in the left lobe of the liver
• Performance status: 0
• Treatment was initiated with FOLFOX + bevacizumab
  • The patient experienced mild neuropathy, significant mucositis, grade 4 neutropenia, and severe diarrhea with the first cycle (suspected DPD deficiency)
  • She subsequently tolerated therapy well with 50% dose reduction of her regimen in addition to dropping the bolus 5-FU and leucovorin.
• Follow-up imaging showed reduction in the size of the liver lesions
• Patient is planned to start maintenance therapy with low-dose capecitabine plus bevacizumab after 8 cycles of FOLFOX

August 2016

• Follow-up CT showed progression in the liver with new lesions
• Performance status: 1
• She began therapy with mFOLFIRI + bevacizumab
• CEA levels stabilized

February 2017

• The patient complained of severe fatigue and additional weight loss. Her performance status remains at 1.
• CT scan revealed progressive disease with 2 new pulmonary nodules in the left lower lobe of the lung and mild progression in the liver.