Addressing the Needs of a Patient with Significant Comorbidity: Newly Diagnosed GIST in the Setting of Chronic Heart Failure

Background

A 55-year-old male presents to his local urgent care for new onset diffuse abdominal pain, persisting over the course of several days. He describes the pain as a cramping sensation and experiences concurrent nausea. He has a history of irritable bowel syndrome, for which he occasionally takes bismuth subsalicylate. The patient denies recent fevers, chills, nausea, and vomiting, and has not had any appetite changes. He also has a past medical history significant for chronic heart failure. The patient reports that he sees his cardiologist regularly, and his most recent echocardiogram measured his left ventricular ejection fraction to be 35%.

After an otherwise unremarkable workup, a CT of the abdomen and pelvis was scheduled for the following week by the urgent care team. The CT revealed a large mass in the greater curvature of the stomach, measuring 11.1 cm x 6.3 cm. The patient was then referred to their local outpatient oncology clinic. CT-guided biopsy of the stomach mass confirmed GIST (positive for DOG1, CD117, and CD34, and negative for desmin, S100 and AE1/AE3). Molecular testing reveals a KIT exon 11 mutation. Staging scans completed after his initial visit revealed multiple masses measuring at least 1 cm in the liver, which is concerning for additional sites of disease.

After a discussion with his local cardiologist regarding his most recent echocardiogram results and need for close follow-up, the patient was subsequently started on imatinib 400 mg BID. Three months after starting imatinib, he presents to the emergency department for progressively worsening shortness of breath with minimal exertion. His physical examination is remarkable for diminished lower lobe breath sounds and 2+ lower extremity pitting edema. A CT of the abdomen and pelvis reveals slightly progressing disease in both his stomach and liver masses. A complete echocardiogram finds his ejection fraction to have significantly decreased to 20%.

Discussion

It is not uncommon for patients to present to their local urgent care or primary care physician with a multitude of vague symptoms. It can be difficult to determine whether these symptoms are related to a pre-existing condition, an expected side effect from a medication, or indicative of an entirely new diagnosis.

While cardiotoxicity is not a common adverse effect of imatinib therapy, it is something for the oncology advanced practice provider (APP) to be aware of, especially with patients who have cardiac-related comorbidities, such as hypertension or congestive heart failure.^1,2 The imatinib package insert informs providers that severe congestive heart failure and left ventricular dysfunction have been reported in patients taking imatinib, and to consider cardiac toxicity, along with hepatic and renal toxicity, with long-term drug use.³

Communication with the patient’s other providers, such as their cardiologist or primary care provider, is key. Oncology patients with other comorbidities should continue to participate in follow-up appointments for all other related specialties. The APP should ensure the patient is also adherent in completing all appropriate imaging and lab work at regular intervals. For patients with pre-existing cardiac conditions, the APP can also consider placing a referral to a cardio-oncologist, if available.¹

If a cardiotoxic event occurs, it is important to pause imatinib therapy until the event has resolved, and consider discontinuing therapy entirely.^1-4 In this particular case, the patient’s CT scan in the emergency department was concerning for slight progression. It is important to note that certain TKIs (particularly vascular endothelial growth factor receptor TKIs such as sorafenib, sunitinib, and pazopanib) are more strongly associated with cardiotoxic adverse events and don’t always present the same as imatinib-related events.⁵ In this case, the APP should be able to conduct a risk vs. benefit discussion with the patient to decide whether to continue imatinib at a reduced dose (400 mg daily) or proceed with next-line therapy sunitinib.^3,4

References

1. Ghias AAP, Bhayani S, Gemmel DJ, Garg SK. Rapidly progressive dyspnea in gastrointestinal stromal tumor (GIST) with imatinib cardiac toxicity. J Community Hosp Intern Med Perspect. 2018;8(2):87-91. Published 2018 Apr 17. doi:10.1080/20009666.2018.1454787
2. Khakoo, AY, Steinert, DM, Patel, SR, Trent, JC. Rare incidence of congestive heart failure (CHF) in gastrointestinal stromal tumor (GIST) and other sarcoma patients (pts) receiving imatinib mesylate (IM) therapy. J Clin Oncol. 2007;25(18):10026-10026. doi:10.1200/jco.2007.25.18_suppl.10026
3. Imatinib [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 3/2024.
4. NCCN Guidelines: Gastrointestinal stromal tumors. Version 2.2024; July 31, 2024.
5. Sayegh N, Yirerong J, Agarwal N, et al. Cardiovascular toxicities associated with tyrosine kinase inhibitors. Curr Cardiol Rep. 2023;25(4):269-280. doi:10.1007/s11886-023-01845-2