Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib.

OBJECTIVES: To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. PATIENTS AND METHODS: A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88-4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16-1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02-0.55; p=0.035) were associated with poorer ORR. CONCLUSION: Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.

The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme.

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.

A multi-institutional evaluation of carboplatin plus docetaxel regimen in elderly patients with advanced gastric cancer.

PURPOSE: Albeit the majority of gastric cancers occur at advanced age, little is known regarding the optimal systemic treatment of elderly patients with advanced gastric cancer (AGC). METHODS: Patients with AGC who were ≥ 65 years old and were treated with carboplatin (area under the curve/AUC 5,on day 1, every 3 weeks) plus docetaxel (75 mg/m(2), on day 1, every 3 weeks) at 3 institutions were included in this retrospective analysis. The efficacy and the safety data of the regimen were analyzed. RESULTS: A total of 30 patients were enrolled. They received 128 cycles of chemotherapy, with a median of 4 cycles (range 2-8). Complete response (CR) and partial response (PR) were observed in 2 (6.7%) and 10 patients (33.3%), respectively, amounting to an overall objective response rate (ORR) of 40%. Seven patients (23.3%) had disease stabilization (SD), and 11 (36.7%) showed disease progression (PD). The most common grade 3-4 toxicity was neutropenia occurring in 19 patients (63.3%). The mean progression-free survival (PFS) was 6.0 ± 0.5 months (95% CI: 5.0-7.4), and the mean overall survival (OS) 12.0 ± 1.0 months (95% CI: 9.2-12.1). CONCLUSION: Carboplatin plus docetaxel seems to be an active and well-tolerated regimen, representing a valuable alternative to cisplatin- and/or fluoropyrimidine-containing regimens for the treatment of elderly patients with AGC.

Identification of prognostic factors in patients with metastatic gastrointestinal stromal tumors.

PURPOSE: Gastrointestinal stromal tumors (GISTs) have a complex biology which is reflected by a marked clinical heterogeneity. Thus, there has been great interest in identifying prognostic factors influencing tumor recurrence and survival. The aim of this study was to identify potential clinical and immunohistochemical prognostic factors that may affect survival and treatment outcomes in patients with metastatic GISTs. METHODS: Between 2000 and September 2011, a total of 41 patients with metastatic GISTs (29 males and 12 females; mean age: 57.4±11.8 years; range 29-74) were referred to the Department of Oncology, Uludag University Medical School. Survival analysis for a number of potential prognostic factors was made with the main outcome results of progression-free survival (PFS) and overall survival (OS7rpar;. RESULTS: The most common sites of isolated metastases comprised the liver (n=18), followed by lymph nodes (n=5), the omentum (n=1), and the mesothelium (n=1). The remaining patients had metastases at multiple sites. Cox regression analysis identified ileal location as the only significant predictor of poor PFS both after first-line (p=0.023) and second-line therapy (p=0.016). Tumor location in the ileum (p=0.025) and S100 immunoreactivity (p=0.041) were both independent predictors of OS. CONCLUSION: Tumor site and S100 positivity were the main significant independent predictors of clinical outcomes in patients with metastatic GISTs treated by standard of care.