Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours

doi:10.1016/j.ejso.2004.06.016

European Journal of Surgical Oncology (EJSO)

Volume 30, Issue 10, December 2004, Pages 1098-1103

https://doi.org/10.1016/j.ejso.2004.06.016 Get rights and content

Abstract

Aims

To analyse the prognostic factors of gastrointestinal stromal tumours (GIST) after a complete resection of the primary tumour.

Patients and methods

Fifty-nine patients who underwent a complete initial resection of a GIST were studied. Peritumoral resections (PTR) were compared to segmental organ resections (SOR). Overall survival (OS) and the disease-free survival (DFS) were calculated using the Kaplan–Meier method.

Results

Primary sites were: stomach (25), small intestine (22), rectum (7), duodenum (5). Two patients had nodal involvement. The median follow-up was 45 months. Local DFS was significantly better after SOR compared to PTR (median 63 vs. 11 months, respectively, p<0.001). Univariate analysis for OS identified the grade (p=0.005) and size (p=0.02) as prognostic factors. Only a high histologic grade was an independent factor (p=0.02) in the multivariate analysis. Out of 49 patients who relapsed, the first recurrence was local only in 12, local and distant in 10 and distant only in 27; only one had a lymph node failure. Recurrences were accessible to curative surgery in 22 cases. OS of patients submitted to complete resection of their recurrence was significantly better than patients whose recurrence could not be resected (median 52 vs. 12 months, respectively, p<0.001).

Conclusion

Complete surgery without rupture remains the mainstay of treatment in patients with localized, resectable disease. A peri-tumoral resection confers a high risk of local recurrence and should be avoided. Lymphadenectomy is not systematic. Grade is the main prognostic factor for OS and can be a decision marker for adjuvant treatment with Gleevec.

Introduction

Gastro-intestinal stromal tumours (GIST) are rare tumours occurring at all levels of the gastrointestinal tract. The advent of GLEEVEC has markedly altered the clinical approach to GIST. It has proven to be effective in metastatic GIST¹ and is also under investigation as a neoadjuvant and adjuvant therapy. Complete responses after GLEEVEC therapy are restricted to a few patients² (4% complete remission) and 15% secondary resistances/year are observed.³ Hence, the initial surgery is crucial to avoid recurrence.

Most GISTs contain a gain-of-function mutation in the c-kit proto-oncogene. Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs and prognostic associations were found with particular KIT mutation types.⁴ Patients enrolled in this study were treated before 1999, consequently, therapy targeting c-kit was not available. The c-kit status is usually unknown at the time of initial resection, especially in case of emergency surgery, and cannot be included during decision-making concerning the optimal surgical strategy.

Incomplete resection is the major factor predictive of a poor prognosis.⁵ Factors influencing survival after a curative tumour resection are controversial. Traditionally, the three key prognostic factors have been mitotic rate, tumour size, and site. Tumours that are small (< or =2 cm) and show mitotic activity not exceeding five mitoses per 50 high-power fields have an excellent prognosis, probably independent of site, although this has not been shown specifically for all sites.⁶ The value of negative margins on the resected organ is uncertain with large GISTs,⁷ which may shed cells from anywhere along their surface directly into the peritoneum. But the surgical procedure and its impact on microscopic margin is probably relevant for small tumours.

The aim of this study was to report the factors influencing the prognosis after complete resection of the primary tumour.

Section snippets

Patients

The hospital charts of all the patients who presented between 1980 and 1998 at the Institut Gustave Roussy (IGR) with a GIST in the stomach, duodenum, small bowel and colon-rectum and who underwent a complete initial resection of the primary tumour were reviewed. Tumours were considered malignant if they had more than five mitoses per 50 high power fields. Morphological criteria were used to classify tumour as GIST. All mesenchymal tumours (spindle cells and epithelioid cells) originating in

Patients charts

One hundred and three patients with GIST were referred to our institution for initial therapy or for follow-up after initial therapy or treatment of recurrences. Forty-four patients who had undergone an initial incomplete resection and/or who had synchronous metastatic disease were excluded from the study. Finally, 59 patients with primary GIST completely resected were included in the study. Among these patients, 12 underwent the initial resection in our institution, 47 were referred for follow

Discussion

Gleevec was first applied to GIST 5 years ago. It has already revolutionized the treatment of patients with metastatic disease.1., 2. But surgery remains the mainstay of treatment in patients with localized, resectable disease and the goal of our study was to clarify its modalities. In case of recurrence, resistances to imatinib have appeared and complete responses are rare,³ so that Gleevec cannot palliate an inadequate initial surgery.

The type of primary surgery did not influence overall

Acknowledgements

We thank Mrs Lorna Saint Ange for editing.

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Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the digestive tract, among which patients with distant metastases tend to have a poor prognosis. This study aimed to develop a model for predicting distant metastasis in GIST patients and to develop two models for monitoring overall survival (OS) and cancer-specific survival (CSS) in GIST patients with metastasis. This would allow us to develop an optimal, individualized treatment strategy.
We reviewed demographic and clinicopathological characteristics data from 2010 to 2017 of patients diagnosed with GIST in the Surveillance, Epidemiology, and End Results (SEER) database. The data of the external validation group was reviewed from the Forth Hospital of Hebei Medical University. Univariate and multivariate logistic regression analyses were used to confirm the independent risk factors for distant metastasis in the GIST patients, and univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors for OS and CSS in the GIST patients with distant metastasis. Subsequently, three web-based novel nomograms were developed, which were evaluated by the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).
Of the 3639 patients who met the inclusion criteria, 418 (11.4%) had distant metastases. The risk factors for distant metastasis in GIST patients included sex, primary site, grade, N stage, tumor size, and mitotic count. For OS, the independent prognosis factors for GIST patients with metastasis included age, race, marital, primary site, chemotherapy, mitotic count, and metastasis at the lung, and for CSS, age, race, marital, primary site, and metastasis at the lung were the independent prognosis factors. Three web-based nomograms were constructed based on these independent factors, respectively. The ROC curves, calibration curves, and DCA were performed in the training, testing, and validation sets which confirmed the high accuracy and strong clinical practice power for the nomograms.
Population-based nomograms can help clinicians predict the occurrence and prognosis of distant metastases in patients with GIST, which may be helpful for clinicians to formulate clinical management and appropriate treatment strategies.
Do microscopic surgical margins matter for primary gastric gastrointestinal stromal tumor?
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Although tumor size and mitotic rate are established prognostic factors for worse survival in patients undergoing surgical resection for gastric gastrointestinal stromal tumors, the impact of microscopic margins, or R1 resection, is not completely established.
Patients who received no neoadjuvant therapy and underwent surgical resection for stage I to III gastric gastrointestinal stromal tumors were identified from the 2010 to 2013 National Cancer Database and divided into 2 cohorts, R0 and R1 resections. Cox proportional hazards ratio and Kaplan Meier survival estimates were utilized to analyze 5-y overall survival.
Of 2,084 patients, those with R1 resection (57, 2.7%) were more likely to have tumors >10 cm (28.1% vs 11.9%, odds ratio 3.51, P = .017) and stage III disease (26.3% vs 11.2%, odds ratio 2.26, P = .047). Although margin status was associated with higher risk tumors, it was not associated with receipt of adjuvant therapy. After multivariate Cox regression, R1 and R0 patients did not have a difference in 5-y overall survival (82.5% vs 88.6%, hazards ratio 1.26, P = .49). When stratified by stage of disease, there remained no difference in survival across all stages when comparing R1 and R0 patients.
Positive microscopic margins are uncommon but do not appear to impact survival outcomes in patients with resected localized gastric gastrointestinal stromal tumors.
Gastrointestinal Stromal Tumors of the Stomach and Esophagus
2019, Surgical Clinics of North America
Citation Excerpt :
In addition to tumor site, size, mitotic rate, and tumor rupture, complete surgical resection of disease is an important prognostic indicator for GISTs. R0 resection, or complete resection of all gross and microscopic disease as determined by pathologic review has been shown in numerous studies to be associated with improved local recurrence rate and overall survival.19–21 Therefore, complete resection should be prioritized in the surgical approach to GISTs.
Hybrid NOTES: Combined Laparo-endoscopic Full-thickness Resection Techniques
2016, Gastrointestinal Endoscopy Clinics of North America
Multivisceral resections for gastrointestinal stromal tumors: Are the risks justifiable?
2015, Surgical Oncology
Surgical resection is the cornerstone of treatment for non-metastatic gastrointestinal stromal tumors (GISTs). Multivisceral resection (MVR) for locally advanced tumors is often required to achieve negative margins. The purpose of this study was to review the peri-operative and long-term oncologic outcomes for patients who required MVR versus single-organ resection (SOR) for GISTs.
All patients who underwent treatment for GISTs at a tertiary cancer center between 2001 and 2011 were identified. Patient characteristics and clinical outcomes were compared using the chi-squared/Fisher's exact test and Student's t-test. Disease-free (DFS) and overall survival (OS) were analyzed using the Kaplan–Meier product-limit method.
33 patients underwent MVR and 77 underwent SOR. Tumors in the MVR group were larger and had a higher mitotic index. MVR patients had longer operative times, greater operative blood loss and more peri-operative complications. There was no significant difference in the final margin status between the two groups (R0 resection: SOR 92.2%, MVR 81.8%, p = 0.1303). 5-year DFS was significantly lower in the MVR cohort (44.4% vs. 78.9%, p = 0.0090), but there was no difference in 5-year OS (80.2% vs. 90.5%, p = 0.2547).
MVR patients had more aggressive tumors and more complications; however, there was no difference in 5-year OS between the MVR and SOR cohorts. These findings support the use of MVR in the appropriately selected patient. Further studies are necessary to fully define its clinical application.
Surgical management of rectal GIST. A case report and a review of literature
2021, Annali Italiani di Chirurgia

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Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours

Abstract

Aims

Patients and methods

Results

Conclusion

Introduction

Section snippets

Patients

Patients charts

Discussion

Acknowledgements

Eur J Cancer

Hum Pathol

Hum Pathol

Surg Oncol

Am J Surg

Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors

N Engl J Med

Comparison of two doses of imatinib for the treatment of advanced gastro intestinal stromal tumour: interim results of a randomised phase II study from the EORTC-STBSG, ISG, AGITG

Proc ASCO

Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors

J Clin Oncol