A new indicator of disease progression in gastrointestinal stromal tumors

Introduction: Neutrophil-to-lymphocyte ratio (NLR) was shown to be prognostic in several solid malignancies. There are limited data about predictive/prognostic value of NLR during targeted therapy of patients with advanced gastrointestinal stromal tumors (GIST). The aim of this study was to asses a clinical value of this ratio in patients with advanced GIST. Methods: Between 2001 and 2016, 385 patients with metastatic/unresectable GIST treated initially with imatinib were included in the analysis. In all patients, the NLR was assessed at the baseline, after 3 months of treatment, and upon disease progression (or last observation). The cutoff values for NLR were set at 2.7 and 5.4. Kaplan-Meier survival probability estimation with log-rank test and Cox proportional hazards model were used for analysis. Results: Median progression-free survival (PFS) on imatinib treatment was 44.8 months, 5-year rate 43%; median overall survival (OS) 87.2 months, 10-year rate 36.3%. NLR >2.7 at baseline was significantly associated with poorer OS and PFS: median OS was 89.3 months (95% confidence interval [CI] 80.2-115) for NLR ratio ≤2.7 vs 59.4 months (95% CI 48.6-82) for NLR >2.7 ( p < .001); median PFS was 59.4 vs 32.7 ( p < .001), respectively. In multivariate model adjusted for mitotic index and driver mutation in the tumor ( KIT exon 11 mutation versus other), NLR ratio was proven to be statistically significant (hazard ratio 1.09; 95% CI 1.01-1.19; p = .030). Among patients with disease progression, NLR >2.7 assessed at the third month of treatment was linked with significantly shorter median time to progression (7.5 vs 19 months). Conclusions: Our results demonstrate the usefulness of NLR as a prognostic and predictive marker as well as a marker for treatment monitoring in patients with advanced GIST treated with imatinib.

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Surgical Management of Advanced Gastrointestinal Stromal Tumors After Treatment With Targeted Systemic Therapy Using Kinase Inhibitors

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.3439 ◽

2006 ◽

Vol 24 (15) ◽

pp. 2325-2331 ◽

Cited By ~ 284

Author(s):

Chandrajit P. Raut ◽

Matthew Posner ◽

Jayesh Desai ◽

Jeffrey A. Morgan ◽

Suzanne George ◽

...

Keyword(s):

Overall Survival ◽

Disease Progression ◽

Stable Disease ◽

Systemic Therapy ◽

Gastrointestinal Stromal Tumors ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Residual Disease ◽

Stromal Tumors ◽

Surgical Result

PurposeWhile targeted inhibitors of tyrosine kinase activity demonstrate dramatic efficacy in the majority of patients with advanced gastrointestinal stromal tumors (GISTs), cure remains elusive and resistance to systemic therapy is a challenge. To assess the role of surgery in multimodality management of GISTs, we studied postoperative outcomes in patients treated with targeted kinase inhibitors for advanced GIST.MethodsWe evaluated outcomes in a single institution series of 69 consecutive patients who underwent surgery for advanced GISTs while receiving kinase inhibitors. Patients were categorized based on extent of disease before surgery (stable disease, limited disease progression, generalized disease progression) and surgical result (no evidence of disease, minimal residual disease, bulky residual disease).ResultsDisease status before surgery was associated with surgical result (P < .0001; median follow-up, 14.6 months). After surgery, there was no evidence of disease in 78%, 25%, and 7% of patients with stable disease, limited progression, and generalized progression, respectively. Bulky residual disease remained after surgery in 4%, 16%, and 43% of the patients with stable disease, limited progression, and generalized progression. Twelve-month progression-free survival was 80%, 33%, and 0% for patients with stable disease, limited progression, and generalized progression (P < .0001). Twelve-month overall survival was 95%, 86%, and 0% for patients with stable disease, limited progression, and generalized progression (P < .0001).ConclusionPatients with advanced GISTs exhibiting stable disease or limited progression on kinase inhibitor therapy have prolonged overall survival after debulking procedures. Surgery has little to offer in the setting of generalized progression.

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Disease Progression Following Imatinib Failure in Gastrointestinal Stromal Tumors: Role of Surgical Therapy

The Oncologist ◽

10.1634/theoncologist.12-4-438 ◽

2007 ◽

Vol 12 (4) ◽

pp. 438-442 ◽

Cited By ~ 9

Author(s):

Faek R. Jamali ◽

Sophie S. Darwiche ◽

Nizar El‐Kinge ◽

Ayman Tawil ◽

Assaad M. Soweid

Keyword(s):

Disease Progression ◽

Surgical Therapy ◽

Gastrointestinal Stromal Tumors ◽

Stromal Tumors

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A new indicator of disease progression in gastrointestinal stromal tumors

Nature Clinical Practice Oncology ◽

10.1038/ncponc0212 ◽

2005 ◽

Vol 2 (7) ◽

pp. 330-331

Keyword(s):

Disease Progression ◽

Gastrointestinal Stromal Tumors ◽

Stromal Tumors

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Pattern of progression and its impact on outcome in patients with gastrointestinal stromal tumors after initial response to imatinib mesylate: A retrospective multicenter long-term follow-up study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.9541 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 9541-9541

Author(s):

J. T. Hartmann ◽

F. Heidel ◽

J. Stoehlmacher ◽

M. Duex ◽

J. R. Izbicki ◽

...

Keyword(s):

Disease Progression ◽

Gastrointestinal Stromal Tumors ◽

Local Treatment ◽

Progression Free Survival ◽

Initial Response ◽

Imatinib Resistance ◽

Kit Mutation ◽

Stromal Tumors ◽

Long Term Follow Up

9541 Background: To investigate the clinical impact of the different types of disease progression (focal v extensive) in patients (pts) with metastatic gastrointestinal stromal tumors (GIST) after initial response to imatinib. Methods: Pts who received imatinib for metastatic GIST at three Cancer Centers and who have been followed up for at least 2.5 years were eligible for the study. Disease progression was classified as focal or extensive as defined by protocol. Responses were evaluated according to WHO criteria. Progression-free survival (PFS) and overall survival (OS) were calculated according to the Kaplan-Meier-method. In three pts with focal progressions, serial biopsies were obtained for mutation analysis. Results: Thirty-eight patients (21 men; mean age 58.4 years; range, 37–73 years) were included in the analysis. After a median follow-up of 31.8 mos, 25 of 38 (65.8%) patients had progressed. Nine of 25 progressions were classified as focal and 16 as extensive. Salvage therapies included dose escalation of imatinib with or without surgical resection. Median and 6- and 12-mos PFS were 11.3 mos, 89%, and 40% in pts with focal progression, and 2.5 mos, 39%, and 32%, in patients with extensive progression, respectively. The median OS was 22.8 mos in pts with extensive progression, and was not reached in pts with focal progression. Two subsequent focal progressions in one pt were associated with 2 different secondary KIT-mutations, whereas non-progressive disease harbored the original KIT-mutation alone. Conclusions: Imatinib resistance seems to be partial in a subset of progressing GIST pts. These pts may benefit from local treatment and imatinib continuation and further investigation of imatinib combinations with other compounds appears warranted. Extensive progression is associated with a dismal survival. No significant financial relationships to disclose.

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Factors Associated With Disease Progression in Patients With Gastrointestinal Stromal Tumors in the Pre-Imatinib Era

American Journal of Clinical Pathology ◽

10.1309/akk3vff610cwm566 ◽

2005 ◽

Vol 124 (5) ◽

pp. 740-748 ◽

Cited By ~ 35

Author(s):

Igors Iesalnieks ◽

Petra Rümmele ◽

Wolfgang Dietmaier ◽

Thomas Jantsch ◽

Carl Zülke ◽

...

Keyword(s):

Disease Progression ◽

Gastrointestinal Stromal Tumors ◽

Stromal Tumors ◽

Factors Associated

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Surgical Management of Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Pediatric and Wildtype GIST Clinic

Journal of Clinical Oncology ◽

10.1200/jco.2016.68.6733 ◽

2017 ◽

Vol 35 (5) ◽

pp. 523-528 ◽

Cited By ~ 22

Author(s):

Christopher B. Weldon ◽

Arin L. Madenci ◽

Sosipatros A. Boikos ◽

Katherine A. Janeway ◽

Suzanne George ◽

...

Keyword(s):

Disease Progression ◽

Surgical Management ◽

Gastrointestinal Stromal Tumors ◽

Proportional Hazards ◽

Tumor Biology ◽

Extent Of Resection ◽

Cox Proportional Hazards ◽

Resection Margins ◽

Wild Type ◽

Stromal Tumors

Purpose Wild-type gastrointestinal stromal tumors (WT-GISTs) that lack KIT or PDGFRA mutations represent a unique subtype of GIST that predominantly affects children. We sought to determine the effect on event-free survival (EFS) of staging variables, extent of resection, and repeat resection of tumors. Methods In 2008, a WT-GIST clinic was established at the National Cancer Institute, allowing the development of a large clinical database. We included participants who underwent resection of WT-GIST. Associations with EFS (ie, freedom from disease progression or recurrence) were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. Results Among 76 participants with WT-GISTs, the median follow-up was 4.1 years. Overall EFS (± SE) was 72.6 ± 5.4% at 1 year, 57.6 ± 6.2% at 2 years, 23.7 ± 6.0% at 5 years, and 16.3 ± 5.5% at 10 years postoperatively. Hazard of disease progression or recurrence was significantly increased for patients with metastatic disease (adjusted hazard ratio [AHR], 2.3; 95% CI, 1.0 to 5.1; P = .04) and > 5 mitoses per 50 high-power fields (AHR, 2.5; 95% CI, 1.1 to 6.0; P = .03), whereas there was no significant effect of negative microscopic resection margins (AHR, 0.9; 95% CI, 0.4 to 2.2; P = 0.86). There was no association between type of gastric resection (ie, anatomic v partial/wedge) and EFS ( P = .67). Repeated resection after the initial resection was significantly associated with decreasing postoperative EFS ( P < .01). Five patients (6%) died after initial enrollment in 2008. Conclusion WT-GIST is an indolent disease, and most patients survive with disease progression. We found no improvement in EFS with more extensive or serial resections. Disease progression or recurrence may be more closely related to tumor biology than surgical management. These data suggest that resections for WT-GISTs be restricted to the initial procedure and that subsequent resections be performed only to address symptoms such as obstruction or bleeding.

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