patient care perspectives

Predicting Gastrointestinal Stromal Tumor Growth and Spread Post Surgery

by Michael C. Heinrich, MD

Overview

The risk of recurrence, growth, and spread of gastrointestinal stromal tumors (GIST) after surgery relates to key variables such as the size, location, and mitotic rate of the primary tumor, as well as the presence of tumor rupture. The optimal duration of adjuvant therapy in relation to an individual’s risk status is an important unanswered question.

Expert Commentary

Michael C. Heinrich, MD

Professor of Medicine
Professor of Cell and Developmental Biology
OHSU Knight Cancer Institute
Oregon Health & Science University School of Medicine
Portland, OR

“One of the reasons for monitoring for recurrence even in the setting of low-risk GIST is that, if such tumors do recur, highly effective medical therapies may be offered. You do not want to let a patient recur and become symptomatic.”

Michael C. Heinrich, MD

GIST cannot be reliably categorized as benign or malignant based on H&E staining, and, in general, the morphology of GIST is much less telling than for common cancers such as breast and colon cancers. GIST that appear malignant microscopically may never return, and tumors that appear benign may ultimately prove fatal. Consequently, GIST are risk stratified using a number of different models. I use the tool developed by Joensuu et al that incorporates the primary tumor size, mitotic count, tumor rupture, and tumor site. One of the advantages of this tool is that the mitotic rate is treated as a continuous variable (eg, mitotic rates of 6 and 26 are treated differently even though they are both >5). Generally, high-risk primary tumors are associated with size greater than 10 cm with any mitotic rate, a high mitotic rate (>5 mitoses/50 HPF), and/or rupture. Rupture is associated with a very high risk of recurrence that is more than 90% independent of other factors. Gastric GIST are associated with a lower risk of recurrence, regardless of size, than GIST in the small intestine, colon, or rectum.

Esophagogastroduodenoscopy and endoscopic ultrasound with the possibility of fine needle aspiration allows gastroenterologists to identify GIST much earlier than in the past. Many gastric GIST are discovered incidentally while a patient is being evaluated for Helicobacter pylori, reflux, or gastritis. For very small resected GIST (eg, <1 cm) determined to pose no risk of recurrence or spread, follow-up generally is not necessary. For larger resected GIST, say 3 to 4 cm, even with low risk of recurrence, a reasonable approach might be abdominal and pelvic computed tomography every 6 months for 3 years and then annually for a few additional years. One of the reasons for monitoring for recurrence even in the setting of low-risk GIST is that, if such tumors do recur, highly effective medical therapies may be offered. You do not want to let a patient recur and become symptomatic.

One area of uncertainty centers on the impact of adjuvant therapy on GIST and the optimal duration of systemic therapy for an individual’s risk status. The fundamental question, which future clinical trials may answer, is whether adjuvant imatinib therapy kills residual GIST cells or if it merely puts them in a state of quiescence from which they can recover. The PERSIST-5 study was a 5-year trial designed to assess the impact of a longer duration of adjuvant therapy to prevent recurrence in patients with resected KIT exon 11–mutant GIST. It included adults at intermediate or high risk of recurrence, and one of the interesting findings was that, as long as these patients remained on imatinib for the entire 5 years, there were no recurrences. For those who did recur, the recurrence was within 2 years of the discontinuation of imatinib. Thus, we must get to the bottom of that phenomenon to understand whether indefinite therapy with imatinib may be warranted and for whom (ie, at what level of risk for GIST recurrence). 

References

Gronchi A, Bonvalot S, Poveda Velasco A, et al. Quality of surgery and outcome in localized gastrointestinal stromal tumors treated within an international intergroup randomized clinical trial of adjuvant imatinib. JAMA Surg. 2020;e200397. doi:10.1001/jamasurg.2020.0397

Joensuu H, Martin-Broto J, Nishida T, Reichardt P, Schöffski P, Maki RG. Follow-up strategies for patients with gastrointestinal stromal tumour treated with or without adjuvant imatinib after surgery. Eur J Cancer. 2015;51(12):1611-1617.

Joensuu H, Vehtari A, Riihimäki J, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265-274.

Mandrioli M, Mastrangelo L, Masetti M, et al. Characterization of malignant gastrointestinal stromal tumors—a single center experience. J Gastrointest Oncol. 2017;8(6):1037‐1045.

Raut CP, Espat NJ, Maki RG, et al. Efficacy and tolerability of 5-year adjuvant imatinib treatment for patients with resected intermediate- or high-risk primary gastrointestinal stromal tumor: the PERSIST-5 clinical trial. JAMA Oncol. 2018;4(12):e184060.

More in GIST

Thumb

GIST

New Directions for Gastrointestinal Stromal Tumor Clinical Research

Clinical Topic Updates by Arun Singh, MD

Newer targeted therapies for patients with gastrointestinal stromal tumors (GIST) are being developed to inhibit primary and drug-resistant KIT/PDG...READ MORE

Thumb

GIST

Resistance-Conferring Mutations With First-Generation Tyrosine Kinase Inhibitors

Clinical Topic Updates by Jonathan C. Trent, MD, PhD

Imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GIST); however, resistance to tyrosine kinase inhibition is a continu...READ MORE

Thumb

GIST

Patients on Second- or Third-line Gastrointestinal Stromal Tumors Therapy: Adverse Effects and Management

Patient Care Perspectives by Michael C. Heinrich, MD

Some adverse effects, such as fatigue and diarrhea, may occur with any of the tyrosine kinase inhibitors (TKIs) used in the treatment of gastrointe...READ MORE

More In Oncology

HER2-Positive Breast Cancer

Recent Developments in HER2-Targeted Therapy

Clinical Topic Updates by Ian Krop, MD, PhD

cGVHD

Prophylactic Strategies in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Expert Roundtables by Sergio A. Giralt, MD; John Koreth, MBBS, DPhil; and Robert S. Negrin, MD