Outcomes in Patients With Metastatic Renal Cell Carcinoma Who Develop Everolimus-Related Hyperglycemia and Hypercholesterolemia : Combined Subgroup Analyses of the RECORD-1 and REACT Trials

In this study we examined the outcome of metastatic renal cell cancer patients with everolimus treatment related hyperglycemia and hypercholesterolemia. All patients were treated in 2 large, international prospective trials, RECORD-1 (REnal Cell cancer treatment with Oral RADOO1 given Daily) and REACT (RADOO1 Expanded Access Clinical Trial in RCC). Patients who experienced these events might have experienced an improved response to everolimus. Background: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. Patients and Methods: Adults with vascular endothelial growth factor refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression free survival for patients who developed hypercholesterolemia or hyperglycemia. Results: In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer-than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant. Conclusion: Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be validated with prospective biomarker studies.Peer reviewe

Serum galectin-3 and ?-1-acid glycoprotein levels in diagnosis and prognosis of idiopathic sudden sensorineural hearing loss

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an otological emergency in which etiopathogenesis remains unclear. A number of disorders is considered as the cause; therefore, different treatment modalities are used without certainty of a cure. The present study aimed to analyse the potential correlation between serum alpha-1-acid glycoprotein (AGP) and galectin-3 levels with ISSNHL, and to investigate markers for guidance of treatment. A total of 55 patients with ISSNHL [29 (52.7%) female, 26 male, mean age, 46.76 +/- 17.68 years] and 47 healthy volunteers [25 (53.2%) female, 21 male, mean age, 43.95 +/- 12.96 years) were included in the study. The complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum galectin-3 and AGP levels were evaluated. The audiological investigation included pure tone average and speech discrimination scores were also recorded before and after corticosteroid treatment. Serum AGP levels in the study group vs. the control group were 64.08 +/- 25.10 and 67.01 +/- 21.59 mg/dl (P=0.53), respectively. Galectin-3 levels were 16.80 +/- 4.55 in the study group and 15.15 +/- 3.74 ng/ml in the control group (P=0.05). Serum galectin-3 levels were significantly correlated with unresponsiveness to treatment (P < 0.001). Galectin-3 is an important biomarker for patients with ISSNHL. Patients with high serum galectin-3 levels may be unresponsive to standard therapy

Prognostic factors in patients with aggressive non-Hodgkin's lymphoma without complete response to first-line therapy

This study was conducted to retrospectively identify the prognostic factors that specifically predict survival rates of patients with aggressive non-Hodgkin's lymphoma who did not achieve a complete response (CR) to first-line therapy. Prognostic factors in terms of survival were analyzed in 76 adult patients with non-Hodgkin's lymphoma who had failed to achieve CR to first-line chemotherapy (CT) regimens administered at Istanbul University, Institute of Oncology, between February 1989 and October 1998. A total of 41 patients were female, and median age was 60 y (range, 18-87 y). Twenty-seven patients (35%) had primary refractory disease (stable disease + progressive disease). A partial response (PR) was demonstrated in 49 (65%). In all, 92% had been administered anthracycline on the basis of computed tomography findings. Of 27 patients with primary refractory disease, 20 died because of initial CT toxicity or disease progression. A total of 10 patients with primary refractory disease underwent second-line CT. CR was observed in only I of those patients. Of the 49 patients who had a PR to first-line therapy, 31 died because of disease progression. Of those patients, 14 underwent second-line CT. Four patients were observed to have a CR. Median overall survival (OS) in all patients was established at 15 mo (range, 11-19 mo), and 5-y OS was 25%. On the other hand, median OS in patients with primary refractory disease was 7.6 mo (range, 5.7-9.4 mo) and was observed to be 17.8 mo (range, 9.4-26.1 mo) in patients with a PR. The difference in survival rates between patients with primary refractory disease and those with a PR was significant (P=.005). Although median OS was 18.1 mo (range, 8.4-27.8 mo) in patients with intermediate-grade histology, it was 6.1 mo (range, 1-11.7 mo) in patients with high-grade histology (P=.001). As a result of univariate analysis, significant prognostic factors associated with OS included histologic grade (intermediate/high) (P=.001), response to initial therapy (primary refractory disease/PR) (P=.005), performance status (0-2/2-4) (P=.024), and International Prognostic Index risk groups (low/low intermediate/intermediate-high/high risk) (P=.004). Multivariate analysis revealed that independent prognostic parameters associated with OS included response to initial therapy (P=.009) and histologic grade (P=.001). Although prognosis is rather poor in patients with high histologic grade and primary refractory disease, patients with a PR have a slightly better prognosis

Predictive Value of Marker Half-life in Relapsed and Nonrelapsed Nonseminomatous Germ Cell Testicular Tumor Patients Undergoing Chemotherapy

Background: The aim of this study was to investigate the influence of a marker half-life (MHL) on relapse in nonseminomatous germ cell testicular tumor patients

Diagnosis and Management of Cornu Cutaneum of Nasal Vestibule: A Rare Case Report

Cornu cutaneum is a relatively uncommon projectile, irregular, hyperkeratotic nodule that can be seen in places such as scalp, forehead, eyelids, ear, nose, lips, and upper extremities which are subjectable to sunlight. Treatment is surgery with radical margins. Excisional biopsy is enough for treatment of the lesion on head and face. However, there is only little literature about cornu cutaneum on the nasal vestibule. We present an 82-year-old male patient with a necrotic, irregular shaped lesion with pedicle on the left nasal vestibule excised and diagnosed as cornu cutaneum

Surveillance Results of Patients with Stage I Nonseminomatous Germ Cell Testicular Cancer

Background: The aim of this study was to evaluate the efficacy of active surveillance after radical orchiectomy in patients with clinical stage I nonseminoma. Patients and Methods: Between 2002 and 2009, the charts of 80 patients who were offered active surveillance were studied retrospectively. Patients underwent clinical, radiologic, and biochemical examinations according to NCCN follow-up guidelines in nonseminoma. Results: 70 of 80 patients who accepted this strategy were analyzed. 12 of the 70 patients (17%) had relapses with a median follow-up of 18.5 months (6-76). Relapses were found in retroperitoneal lymph nodes in 3 patients. 5 patients had marker relapse, and 4 patients developed both marker relapse and retroperitoneal lymph node metastases. 10 of the 12 patients (83%) had relapsed within 1 year. There were no statistically significant differences in lymphovascular invasion and germ cell components between relapsed and non-relapsed patients. 11 of the 12 patients were treated with cisplatin-based combination chemotherapy, and 1 patient underwent retroperitoneal lymph node dissection. Only 2 patients underwent primary retroperitoneal lymph node dissection for rest nodules. Conclusions: Surveillance could be a reliable strategy in compliant stage I nonseminoma patients. Recurrences can be detected early and treated successfully