Mahmut Ucar

Albumin-globulin Ratio for Prediction of Long-term Mortality in Lung Adenocarcinoma Patients

BACKGROUND Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. MATERIALS AND METHODS This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/ (total protein-albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. RESULTS The mean survival time for each tertile was: for the 1st 9.8 months (95%CI:7.765-11.848), 2nd 15.4 months (95%CI:12.685-18.186), and 3rd 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. CONCLUSIONS Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma.

Clinicopathological characteristics and prognosis of patients according to recurrence time after curative resection for colorectal cancer.

PURPOSE To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. MATERIALS AND METHODS We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). RESULTS The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). CONCLUSIONS Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.

Is sunitinib-induced hypothyroidism a predictive clinical marker for better response in metastatic renal cell carcinoma patients?

Background: The main goal of this study was to examine whether the occurrence of hypothyroidism during sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. Methods: The study enrolled 81 patients with pathologically proven mRCC who were treated with sunitinib between March 2008 and June 2013.Thyroid function evaluation comprised (free-thyroxine) FT4 and thyroid-stimulating hormone (TSH) before treatment and at day 1 of each 6-week cycle. Survival analysis was performed using the Kaplan–Meier method, and the differences among the groups were determined using the log-rank test. Results: Hypothyroidism occurred in 30 (37%) of 81 patients within a median 3 months (range 1–18) of treatment initiation. There was a statistically significant correlation between the occurrence of hypothyroidism during treatment and the rate of objective remission (ORR) (hypothyroid patients vs euthyroid patients: 46.7 vs 13.7%, respectively; P = 0.001). Median progression-free survival (PFS) was 10 (95% CI 6.13–13.8) months in the euthyroid patients, and 17 (95% CI 9.33–24.6) months in the hypothyroid patients (P = 0.001). The median overall survival (OS) was 39 (95% CI 25.4–52.5) months in the hypothyroid patients and 20 (95% CI 14.7–25.2) months in the euthyroid patients (P = 0.019). Conclusions: The occurrence of hypothyroidism during treatment in patients was significantly associated with longer PFS, OS and better ORR in the current study.

Is Late Recurrence a Predictive Clinical Marker for Better Sunitinib Response in Metastatic Renal Cell Carcinoma Patients

BACKGROUND We investigated the clinicopathological features in patients with recurrent renal cell carcinoma (RCC) within 5 years or more than 5 years after nephrectomy and determined predictors of overall survival (OS) and progression-free survival (PFS) after disease recurrence in the administration of first-line sunitinib in the treatment of metastatic RCC (mRCC). PATIENTS AND METHODS In this study we enrolled 86 Turkish patients with mRCC who received sunitinib. Univariate analyses were performed using the log rank test. RESULTS Fifty-six patients (65%) were diagnosed with disease recurrence within 5 years after radical nephrectomy (early recurrence) and 30 patients (35%) were diagnosed with recurrence more than 5 years after radical nephrectomy (late recurrence). Fuhrman grade was statistically significantly different between the 2 groups (P = .013). The late recurrence patients were significantly associated with the Memorial Sloan Kettering Cancer Center favorable risk group compared with patients with early recurrence (P = .001). There was a statistically significant correlation between recurrence time and the rate of objective remission (ORR) (the late recurrence group vs. the early recurrence group: 43.3% vs. 14.3%, respectively; P = .004). From the time of disease recurrence, the median OS was 42.0 (95% confidence interval [CI], 24.4-59.5) months in the late recurrence group, and 16 (95% CI, 11.5-20.4) months in the early recurrence group (P = .001). Median PFS was 8 (95% CI, 4.05-11.9) months in the early recurrence group, and 20 (95% CI, 14.8-25.1) months in the late recurrence group (P ≤ .001). CONCLUSION The study demonstrated a potential prognostic value of late recurrence in terms of PFS, OS, and ORR.

Analyses of multiple factors for determination of "selected patients" who should receive rechallenge treatment in metastatic colorectal cancer: a retrospective study from Turkey.

BACKGROUND Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin- based regimens as rechallenge third and fourth-line therapy. MATERIALS AND METHODS Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meir and Cox-regression methods. RESULTS Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.7 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy≥12 months (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. CONCLUSIONS This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ≥12 months PFS on receiving first line therapy.

Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study

ABSTRACT Background: There are insufficient predictive markers for renal cell carcinoma (RCC). Methods: A total of 308 metastatic RCC patients were analyzed retrospectively. Results: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35 months (p < .001) and 21.0 versus 11.36 months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. Conclusions: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

Can we effective use sym004 in tumours harboring EGFR extracellular domain mutations

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death (1). The therapeutic options available for the treatment of metastatic CRC have significantly increased over the past years. Together with the advances in surgical techniques, the introduction of irinotecan and oxaliplatin first and drugs targeting vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR) later, have led to a median overall survival (OS) now approaching 30 months (2).

Are Rogerofenib and Nilotinib Effective for Advanced Gastrointestinal Stromal Tumor (GIST) Patients who have Already been Given Main Treatments

Patients with GISTs most commonly have KIT and PDGFRA mutations. The therapeutic agents are determined based on these sites of mutation. Imatinib and sunitinib are proven to be effective against GIST, and these agents are now the standard treatment options for GISTs. Moreover, several novel molecular-targeted agents are under development, particularly regorafenib and nilotinib which have phase III trials. In these trials, it has been shown to contribute of survival with regorafenib but longer survival has not obtained with nilotinib. We have two cases who were responder with regorafenib and nilotinib in the fifth-line therapy. First case, a 45-year-old male patient who had GIST in small intestine with multipl liver metastases. C-KIT gene mutation analysis was performed on the pathology preparation which has indicated an exon 11 deletion. In the immunohistochemical evaluations, it was found that there was positive staining for CD34 and SMA. Imatinib 400 mg/day had been initiated and it had been used for 7 years. After progression imatinib dose was increased to 800 mg/day, then the patient was shifted to treatment with sunitinib, then treated with sorafenib for 14 months, 2 months, 1 month, respectively. An ileus had occured after a month of sorafenib treatment. This was considered as clinical progression and then the patient was shifted to treatment of regorafenib (160 mg/day). The ileus symptoms markedly regressed on the 7th day of regorafenib treatment and completely resolved on the 14th day (Figure 1). The patient died at the 10th month of treatment with regorafenib due to liver failure. Second case, a 40-year-old female patient who had GIST in stomach with multipl liver metastases. C-KIT and PDGRFA gene mutation analysis was performed on the pathology preparation which has indicated no mutation LETTER to the EDITOR