Is Peritoneal Tumor Penetration of Prognostic Importance in Gastrointestinal Stromal Tumors?

BACKGROUND: Peritoneal tumor penetration (PP) strongly affects prognosis in gastrointestinal carcinomas. In gastrointestinal stromal tumor (GIST), its significance in the absence of tumor rupture has not been subjected to detailed analysis. METHODS: Patients undergoing complete resection for non-metastatic GIST from 2000 to 2017 were identified in the regional sarcoma database at Oslo University Hospital. Patients with extraperitoneal tumors (esophagus, rectum) or ruptured tumors were excluded from the study. Rupture was defined according to the Oslo criteria, and PP was assessed via routine histopathologic examination by sarcoma pathologists. RESULTS: The study enrolled 341 patients. The median follow-up period was 51 months (range 0-175) months. In 82 (24%) of the 341 patients, PP was recorded. There were 32 recurrences, 9 in patients with PP and 23 in patients without PP. Despite statistically significant associations between PP and established risk factors (size, mitotic index, non-gastric location), the 5-year recurrence-free survival rate did not differ between the patients with PP (86%) and those without PP (90%) (hazard ratio 1.25; 95% confidence interval 0.58-2.70; P = 0.577). Adjuvant imatinib was administered to 53 of 97 patients in the high-risk category. The recurrence rates did not differ between the PP-positive and PP-negative patients in either group. CONCLUSIONS: In GIST, PP without tumor rupture appears not to influence prognosis. This lack of prognostic significance may reflect unexplored differences between epithelial and mesenchymal malignancies.

Relationship between R1 resection, tumour rupture and recurrence in resected gastrointestinal stromal tumour.

BACKGROUND: According to guidelines, adjuvant treatment or re-excision should be considered after R1 resection of gastrointestinal stromal tumours (GISTs). However, the prognostic significance of R1 resection is uncertain and tumour rupture confounds its assessment. Here, the impact of positive margins was examined and related to rupture in a population-based cohort. METHODS: Patients undergoing surgery for non-metastatic GIST since 2000 were identified in the sarcoma database of Oslo University Hospital. Margins were coded according to the residual tumour (R) classification and tumour rupture defined according to the Oslo criteria. RESULTS: Among 410 patients, there were 47 who underwent R1 resection and 52 had tumour rupture. The relative risk of R1 resection with rupture was 3·55 (95 per cent c.i. 2·09 to 6·03; P < 0·001). In patients without rupture, there was no difference in estimated 5-year recurrence-free survival after R0 versus R1 resection (87·6 versus 93 per cent; hazard ratio (HR) 0·71, 95 per cent c.i. 0·17 to 2·98; P = 0·638); nor was there any difference among patients with rupture (37 versus 31 per cent; HR 1·31, 0·68 to 2·54; P = 0·420). In multivariable analysis, tumour rupture but not R1 resection was independently associated with recurrence. Twenty-four patients at very low, low or intermediate risk did not receive adjuvant imatinib after R1 resection and remained recurrence-free. CONCLUSION: Positive resection margins are strongly associated with tumour rupture. R1 resection does not independently influence prognosis. Adjuvant imatinib may not be justified after R1 resection in the absence of tumour rupture or other high-risk features.

Genotype and risk of tumour rupture in gastrointestinal stromal tumour.

BACKGROUND: Tumour rupture is a strong predictor of poor outcome in gastrointestinal stromal tumours (GISTs) of the stomach and small intestine. The objective was to determine whether tumour genotype was associated with risk of rupture. METHODS: Rupture was classified according to the definition proposed by the Oslo Sarcoma Group. Since January 2000, data were registered retrospectively for all patients at Oslo University Hospital undergoing surgery for localized GIST of the stomach or small intestine. Tumour genotype was analysed by Sanger sequencing. RESULTS: Two hundred and nine patients with mutation data available were identified. Tumour rupture occurred in 37 patients. Among the 155 patients with KIT exon 11 mutations, an increased risk of rupture was observed with a deletion or insertion-deletion (25 of 86, 29 per cent) compared with substitutions (5 of 50, 10 per cent) or duplications/insertions (2 of 19, 11 per cent) (P = 0·014). Notably, rupture occurred in 17 of 46 tumours (37 per cent) with deletions involving codons 557 and 558 (del557/558) versus 15 of 109 (13·8 per cent) with other exon 11 mutations (P = 0·002). This association was confined to gastric tumours: 12 of 34 (35 per cent) with del557/558 ruptured versus six of 77 (8 per cent) with other exon 11 mutations (P = 0·001). In multivariable logistic regression analysis, del557/558 and tumour size were associated with an increased likelihood of tumour rupture, but mitotic count was not. CONCLUSION: Gastric GISTs with KIT exon 11 deletions involving codons 557 and 558 are at increased risk of tumour rupture. This high-risk feature can be identified in the diagnostic evaluation and should be included in the assessment when neoadjuvant imatinib treatment is considered.