Disclosures: Gronchi reports personal fees from Bayer, Novartis Oncology and Pfizer, and grants/personal fees from Eli Lilly, Nanobiotix and PharmaMar. Please see the study for all other authors’ relevant financial disclosures.
June 26, 2020
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Tumor rupture linked to worse outcomes among patients with GIST

Disclosures: Gronchi reports personal fees from Bayer, Novartis Oncology and Pfizer, and grants/personal fees from Eli Lilly, Nanobiotix and PharmaMar. Please see the study for all other authors’ relevant financial disclosures.
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Tumor rupture appeared associated with shorter OS among patients treated with or without imatinib after surgery for gastrointestinal stromal tumors, or GIST, according to results of a post-hoc observational study published in JAMA Surgery.

However, researchers found no association between microscopic margin status without tumor rupture and shorter survival.

“It was not clear how to interpret the presence of a positive microscopic margin on the surgical specimen of a resected GIST, which was the implication for management as few data were available and conflicting,” Alessandro Gronchi, MD, researcher in the department of surgery at Fondazione IRCCS Institute Nazionale dei Tumori, told Healio. “It has now been clarified that positive surgical margins after surgery for GIST are not associated with worse outcome and should not be factored in the decision for adjuvant therapy or reexcision, with the only exception of GIST located on the rectum. On the contrary, tumor rupture is confirmed to be associated with a much worse outcome for GIST located at any site, regardless of adjuvant therapy use.”

Alessandro Gronchi, MD
Alessandro Gronchi

Researchers lacked a clear understanding of the association between quality of surgery and OS among patients with localized GIST.

For this reason, Gronchi and colleagues pooled data from a randomized, open-label, phase 3 study including 908 patients (median age, 59 years; range, 18-89; 51.4% men) who underwent surgery for primary GIST and received either 400 mg daily adjuvant imatinib for 2 years or no adjuvant treatment. Patients demonstrated intermediate or high risk for relapse with no evidence of residual disease and no prior malignancies or concurrent/severe/uncontrolled medical conditions.

Researchers stratified randomization according to cancer center, risk category, tumor site and quality of surgery, defined as macroscopic complete resection with negative margins (R0) vs. positive microscopic margins resection (R1). Researchers included tumor rupture in the R1 category and in separate analysis. They assessed risk for death with and without imatinib according to margins status.

OS, estimated by the Kaplan-Meier method and compared between R0 and R1 using Cox models adjusted for treatment and stratification factors, served as the primary endpoint.

Median follow-up was 9.1 years (interquartile range, 8-10).

Overall, 17.8% of patients had R1 resection and nearly 60% of those patients experienced tumor rupture.

Results showed 5-year OS rates of 93.9% (95% CI, 91.8-95.4) among patients with R0 resection and 84.4% (95% CI, 77.7-89.3) among patients with R1 resection. Ten-year OS rates were 82.6% (95% CI, 79.2-85.5) with R0 resection vs. 64.4% (95% CI, 55.1-72.3) with R1 resection.

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Researchers observed significant differences in OS among patients with an R1 vs. R0 resection overall (HR = 2.05; 95% CI, 1.45-2.89), as well as with adjuvant imatinib (HR = 2.65; 95% CI, 1.45-2.89) and without adjuvant imatinib (HR = 1.86; 95% CI, 1.16-2.99). However, when researchers excluded tumor rupture, the difference in OS between R1 and R0 resection disappeared (HR = 1.05; 95% CI, 0.54-2.01).

In addition, RFS differed significantly among patients with an R1 vs. R0 resection overall (HR = 1.98; 95% CI, 1.55-2.53), with adjuvant imatinib (HR = 2.32; 95% CI, 1.64-3.3) and without adjuvant imatinib (HR = 1.81; 95% CI, 1.29-2.54). The difference in RFS between resections disappeared when researchers excluded patients with tumor rupture (HR = 1.35; 95% CI, 0.91-1.99).

A central surgery review including 697 patients showed similar results.

Study limitations included a lack of data on how many surgeons were involved in the study and the median number of operations per surgeon.

“We will continue monitoring this topic, but no specific further research is planned at this stage,” Gronchi said.

For more information:

Alessandro Gronchi, MD, can be reached at Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; email: alessandro.gronchi@istitutotumori.mi.it.