Multidisciplinary Management of GIST

Jonathan Trent, MD, PhD: Multidisciplinary management of patients with GIST is generally optimal. Patients should be managed at a GIST center where they have access to surgeons, radiologists, as well as pathologists and nurses who are experienced with gastrointestinal stromal tumor. This is evidence in this case of a patient with GIST who initially responded to imatinib, and we saw regression of a solitary liver metastasis. These are the types of patients who benefit from multidisciplinary resection of a metastatic lesion, as long as it’s responding to a TKI, like imatinib.

Multidisciplinary management of patients with GIST is really optimal. This requires good communication between the surgeons, the pathologists, the radiologists, and the medical oncologists. We accomplish that often by multidisciplinary tumor boards, where all of the GIST specialists meet together in 1 room to go over a patient’s case from all of their individual expertise. At the end of the conference, we have a plan in place that takes advantage of published literature and our individual experiences, to give the patient really the best chance of surviving the longest from gastrointestinal stromal tumor.

The nurse and the nurse practitioner are critical members of the multidisciplinary team. The nurse and the nurse practitioner may be the first one to get a phone call from the patient who has developed a toxicity. For instance, if the patient has developed hypertension, the nurse or nurse practitioner may be able to call in an antihypertensive agent, such that the hypertension doesn’t get out of control and the patient doesn’t have long-term toxicity from hypertension.

GIST patients are often co-managed by a community oncologist and a GIST specialist at an academic center. This co-management is critical because at the academic center, we have a multidisciplinary GIST team that can help delineate the treatment plan at the time of diagnosis, ensure the correct diagnosis, and determine the appropriate therapeutic options and monitoring going forward. After the patient has been on therapy for some time, the patient may develop resistance, and referral to a GIST specialty center could help determine whether there’s a clinical trial available or a new agent that might make sense for this patient.

Referral to a GIST center also allows in-depth mutation testing of the patient’s tumors. This is critical because GIST now really is a category of 9 or 10 different types of GIST, that are characterized by their individual unique mutations. The most common mutation is the gene called KIT, which we treat because it’s sensitive to imatinib. However, if a patient has another common mutation, such asPDGFRA D842V, that mutation is generally resistant to imatinib, and the patient should be referred to a GIST center for a clinical trial.

There are other rare mutations such asRAFandPi3K, which could be treated by an alternative targeted therapy such as a RAF inhibitor or a Pi3K inhibitor. And then there’s this type of GIST called SDH-deficient GIST that is much more difficult to manage, and we’re really starting to really try to understand it at a biological level. These tumors may be more sensitive to a medication like regorafenib, rather than imatinib.

Transcript edited for clarity.

September 2014

• A 64-year old Caucasian male presented with abdominal pain and 3-month history of fatigue
  • PMH was remarkable for hypertension well-controlled with a beta-blocker
  • No family history of cancer
  • He could perform all activities independently
• Abdominal CT findings:
  • 12-cm mass arising from the stomach and involving the cardia, fundus, and body of the stomach
  • 7-cm solitary mass in the left lobe of the liver
• Biopsy results:
  • Gastric GIST with liver metastases
  • IHC positive for CD117 (c-KIT), molecular analysis showed exon 9 deletion
  • Mitotic activity, high with >5 mitoses/50 HPFs
• Treatment was initiated with neoadjuvant imatinib 600 mg daily for 5 months
  • The primary tumor was stable during this time, the liver mass size decreased from 7 cm to 4 cm
• The patient was referred to a surgeon and underwent hepatectomy for the liver metastasis
  • Following surgery, R0 resection with clear margins
• Treatment was initiated with imatinib 800 mg daily

August 2016

• Abdominal CT imaging findings:
  • Multiple peritoneal implants
  • A new small nodule (<1 cm) in the liver
• The patient could perform all activities independently with small occasional breaks, but could not perform physically strenuous activities
• He was switched to sunitinib 37.5 mg daily

February 2017

• At his 6-month follow-up, the patient was still able to perform most non-strenuous activities independently; however, the frequency of being able to do so had declined significantly
• Abdominal CT scan showed progression in multiple peritoneal implants; the liver nodule increased in size to 2 cm
• He was referred to an academic center
  • His treatment was switched to regorafenib 160 mg, 3 weeks on, 1 week off
• The patient appeared to tolerate therapy well, after initial dose modification due to diarrhea experienced during the second week of therapy
• At the 6-month follow-up:
  • Abdominal CT scan showed slight reduction in the peritoneal implants
  • The liver nodule was no longer visible