Amino acids in transmembrane helix 1 confer major functional differences between human and mouse orthologs of the polyspecific membrane transporter OCT1.

Organic cation transporter 1 (OCT1) is a membrane transporter that affects hepatic uptake of cationic and weakly basic drugs. OCT1 transports structurally highly diverse substrates. The mechanisms conferring this polyspecificity are unknown. Here, we analyzed differences in transport kinetics between human and mouse OCT1 orthologs to identify amino acids that contribute to the polyspecificity of OCT1. Following stable transfection of HEK293 cells, we observed more than twofold differences in the transport kinetics of 22 out of 28 tested substrates. We found that the ß2-adrenergic drug fenoterol was transported with eightfold higher affinity but at ninefold lower capacity by human OCT1. In contrast, the anticholinergic drug trospium was transported with 11-fold higher affinity but at ninefold lower capacity by mouse Oct1. Using human-mouse chimeric constructs and site-directed mutagenesis, we identified nonconserved amino acids Cys36 and Phe32 as responsible for the species-specific differences in fenoterol and trospium uptake. Substitution of Cys36 (human) to Tyr36 (mouse) caused a reversal of the affinity and capacity of fenoterol but not trospium uptake. Substitution of Phe32 to Leu32 caused reversal of trospium but not fenoterol uptake kinetics. Comparison of the uptake of structurally similar ß2-adrenergics and molecular docking analyses indicated the second phenol ring, 3.3 to 4.8 Å from the protonated amino group, as essential for the affinity for fenoterol conferred by Cys36. This is the first study to report single amino acids as determinants of OCT1 polyspecificity. Our findings suggest that structure-function data of OCT1 is not directly transferrable between substrates or species.

Multidrug refractory aggressive metastatic TFE3 (+) renal cell carcinoma: A case report.

BACKGROUND: Transcription factor E3 (TFE3) related renal cell carcinomas constitute a very small percent of all renal tumors in adults. Prognosis mainly depends on the stage of the disease at the time of diagnosis which is often poor. There is yet to be a standardized treatment protocol. Treatment options include agents identical to TFE3(-) cell renal carcinoma treatment. We present a case of a young woman with a rapidly progressing metastatic TFE3 (+) renal cell carcinoma. CASE REPORT: A 31 year old female presented with abdominal mass, distension, nausea. Initial tests and tumor markers found to be normal. Abdominal CT scan revealed a left retroperitoneal mass along with three other neighboring masses in liver manifesting as metastases. Trucut biopsy and immunohistochemical staining confirmed the retroperitoneal mass as TFE3 (+) renal cell carcinoma.Management and outcome: Sunitinib, pazopanib, nivolumab, axitinib treatments are consecutively given after surgery. It is noteworthy that rapid progression was observed under nivolumab treatment. DISCUSSION: During surveillance, rapid progression is noted under consecutive immunotherapy which was unexpected. Thus, there is a need for more standardized treatment protocols and invention of new agents for management of TFE3 (+) renal cell carcinoma.

Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma.

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p < 0.001) and M65 (384.2 vs. 179.1 U/L, p < 0.001) concentrations were significantly higher in patients with advanced nasopharyngeal carcinomas than in controls. receiver operating characteristic (ROC) analysis showed that a cutoff for M30 of 225 U/L had a sensitivity of 62.5% and a specificity of 73.9% (area under the curve (AUC) = 0.592, 95% confidence interval (CI) 35.3-83.2, p = 0.44), while a cutoff for M65 of 423.4 U/L had a sensitivity of 75.1% and a specificity of 65.6% (AUC = 0.562, 95 % CI 36.0-76.5, p = 0.60). However, serum M30 and M65 were not important prognostic factors for progression-free survival. There were no statistically significant correlations between serum M30 and M65 concentrations and clinicodemographical variables. Serum M30 and M65 concentrations were found to have a diagnostic value in nasopharyngeal cancer. However, neither M30 nor M65 serum levels played a prognostic role in the outcome in nasopharyngeal cancer patients.

Efficacy and safety of sorafenib in adult metastatic osteosarcoma patients.

BACKGROUND: There are limited data on the efficacy of targeted therapy in metastatic osteosarcoma. The goal of this study was to assess the effectiveness of sorafenib in adult patients with heavily pretreated metastatic osteosarcoma. METHOD: Patients with metastatic osteosarcoma aged more than 18 years were assessed retrospectively. The patients' clinical, pathological, and therapeutic data were collected. For survival analysis, Kaplan-Meier models were used. RESULTS: The research involved 15 patients. The ratio of male and female patients was 2/1, with a median age of 25 years (range: 19-64 years). The most common primary tumor localization was the extremities (66.6%). Fourteen (93.3%) patients had previously received palliative chemotherapy and six (40%) patients had palliative radiotherapy. The median progression-free survival was found as 5.5 months (95% confidence interval, 1.3-9.7). A stable response was observed in seven (46.6%) patients and progressive disease in eight (53.4%) patients. Grade 1-2 toxicities were detected in 50% of the patients, while grade 3-4 toxicities were observed in 14.3% of the patients. CONCLUSIONS: We demonstrated real-life results of sorafenib for disease management in pretreated adult patients with metastatic osteosarcoma in the study. Sorafenib was effective for disease control and well tolerated in the patients. Sorafenib may be a treatment option for disease control after the disease progresses with chemotherapy in patients with metastatic osteosarcoma.

Single-agent temozolomide as salvage therapy in heavily pretreated metastatic sarcoma patients.

BACKGROUND: Treatment options for patients with metastatic sarcoma are limited. The goal of this study was to investigate the effectiveness of temozolomide in pretreated patients with soft tissue sarcoma. METHODS: We recorded the pathological, clinical, and treatment data of the patients with metastatic soft tissue sarcoma retrospectively. We evaluated the efficacy and side effects of temozolomide in this patient group. RESULTS: This study involved 16 patients. The average age was detected as 48 (21-73) years. Six (37.5%) patients had de-novo metastatic disease at diagnosis. Primary of tumors had originated from intra-abdominal (43.7%), extremity (31.3%), head-and-neck (12.5%), and intrathoracic (12.5%) regions. The patients previously had received at least two different chemotherapy regimens (75%), pazopanib (50%) and palliative radiotherapy (31.3%). Temozolomide-related median progression-free survival time was found as 3.5 (95% CI, 2.6-4.3) months. One patient (6.3%) had a partial response, while four patients (25%) had stable disease. Nine individuals (56.3%) had grade 1-2 adverse events, while one patient (6.3%) had grade 3-4 adverse events. CONCLUSIONS: We observed that temozolomide was well tolerated but had limited efficacy in the treatment of metastatic sarcoma patients. In patients with extensively pretreated soft tissue sarcoma, temozolomide may be considered a therapeutic option as a single-agent.

Cisplatin-docetaxel induction chemotherapy for patients with nasopharyngeal carcinoma in a non-endemic cohort.

This is the report on our clinic's 15 years of experience (2004-2018) on nasopharyngeal carcinoma (NPC), treated with induction chemotherapy (IC) and subsequent concomitant chemoradiotherapy (CCRT), comprising population characteristics and treatment outcomes of 203 patients with non-metastatic NPC. IC comprised docetaxel (75 mg/m2) and cisplatin (75 mg/m2) combination (TP). Concurrent cisplatin (P) was applied either weekly (40 mg/m2, 32 cases) or every-3-week (100 mg/m2, 171 cases). The median follow-up duration was 85 months (range, 5-204 months). Overall and distant failure rates were observed in 27.1% (n = 55) and 13.8% (n = 28) patients, respectively. The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 84.1%, 86.4%, 75%, and 78.7% respectively. The overall stage was an independent prognostic factor for the LRRFS, DMFS, DFS, and OS. The WHO histological type was a prognostic factor for the LRRFS, DFS, and OS. Age was a prognostic factor for the DMFS, DFS, and OS. Concurrent P schedule was independent prognostic only the LRRFS.

Therapeutic efficacy of high-dose chemotherapy with autologous stem-cell transplantation in 44 relapsed or refractory germ-cell tumor patients: A retrospective cohort study.

Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory germ-cell tumors. Therefore, selecting the best patient group for this treatment is critical. This study aimed to determine the factors that affect survival in our relapsed/refractory GCT cohort who received HDCT and autologous stem-cell transplantation. Between September 2010 and 2020, we included in the study 44 relapsed/refractory male patients with GCT treated with HDCT plus autologous stem-cell transplantation. The patients' demographic features, clinical characteristics, and treatment outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with survival. The median age of all cohorts was 28 years. Thirty-six patients had nonseminomatous tumors, and 8 patients had seminomatous tumors. The most common primary tumor sites were the gonads (75%), followed by the mediastinum (15.9%) and the retroperitoneum (9.1%). After HDCT, 11 patients had a complete response, 12 patients had a partial response, and 17 patients had a progressive disease, respectively. About 23 patients (52.3%) experienced at least 1 treatment-related grade 3 to 4 nonhematological toxicity. About 4 patients (10%) died due to HDCT-related toxicity. The total group's median progression-free survival (PFS) was 7 months, and the median overall survival (OS) was 14.9 months. Primary tumor site (hazard ratio [HR]: 1.84; P = .028), type of HDCT regimen (HR: 0.35; P = .010), and best response to HDCT (HR: 11.0; P < .0001) were independent prognostic risk factors for PFS. The only independent prognostic risk factor associated with OS was the best response to HDCT (HR: 6.62; P = .001). The results of the study promise the best response to HDCT as a primary measure for predicting survival in relapsed/refractory GCT. In contrast, primary mediastinal GCT is not a good candidate for HDCT. Furthermore, a carboplatin-etoposide regimen in combination with cyclophosphamide and paclitaxel may improve PFS.

Perceptions and Expectations: A Study on Prognostic Perception and Quality of Life in Patients With Metastatic Renal and Bladder Cancer.

PURPOSE: Durable complete response rates for metastatic renal cell carcinoma (mRCC) and metastatic bladder cancer (mBC) are low despite new therapy. Palliative care focuses on life extension and quality of life (QoL), not cure. This study aims to investigate patients' perceptions of treatment outcomes in mRCC and mBC and to assess the influence of QoL and optimism levels on these perceptions. METHODS: From March 15, 2023, to January 15, 2024, a multicenter, cross-sectional online survey was carried out, targeting patients diagnosed with mRCC and mBC. The survey comprised structured questions aimed at evaluating perceptions concerning disease cure, symptom improvement, daily activity performance, and life extension due to treatment. Additionally, to evaluate optimism and QoL, the European Organization for Research and Treatment of Cancer 30.3 QoL questionnaire and life orientation test were implemented. Study on patients' perceptions of treatment outcomes in metastatic kidney and bladder cancer shows high optimism, inaccurate cure beliefs. RESULTS: In total, 169 patients participated in the survey; the majority of the patients stated their general health status as good (72.2%) and excellent (13.6%). Patients who rated their overall health status as good-excellent had a higher median general QoL and optimism score compared with those who rated it as fair-poor. In all, 85.2% of patients considered the possibility of a cure very likely or likely. Most participants believed treatment could provide symptom relief (30.2% very likely, 49.1% likely), enhanced ability to perform daily activities (28.4% very likely, 55.6% likely), and life extension (32.5% very likely, 53.3% likely). Patients responding very likely and likely to these questions regarding treatment outcomes had higher QoL and optimism scores than those responding a little likely and not possible. CONCLUSION: The majority of patients with mRCC and mBC held inaccurate beliefs about treatment outcomes. Better QoL and optimism were associated with increased inaccuracy.

Efficacy of the VIT (vincristine, irinotecan and temozolomide) regimen in adults with metastatic Ewing sarcoma.

The goal of the research was to investigate if a combination of vincristine, irinotecan and temozolomide (VIT) could benefit adult patients with metastatic Ewing sarcoma who had already been heavily pretreated. Metastatic Ewing sarcoma patients had their data retrospectively analyzed. The patients' clinical, radiological and therapeutic data were recorded. Survival analyzes were performed with these data. The study enlisted the participation of sixteen patients. The average age was 25 years old (range: 20-42). The lung was the most prevalent metastatic location (81.3%). Patients had received at least two distinct chemotherapy combinations (87.5%) and palliative radiotherapy (37.5%) before receiving the (VIT) combination. The Median progression-free survival time was found as 3.4 (95% CI, 1.8-4.9) months. Five patients (31.3%) experienced a partial response, while the remaining patients (68.7%) had progressing disease. Thirteen individuals (81.3%) had grade 1-2 adverse events, whereas five (31.3%) had grade 3-4 adverse events. Hematological complications were the most common side effects (87.5%). Median overall survival was calculated as 5.6 (95% CI, 3.6-7.5) months in the patients after the beginning of VIT regimen. We demonstrated the efficacy of the VIT regimen in adult patients with metastatic Ewing sarcoma in this research. In these extensively pretreated patients, toxicities were a concern. Metastatic Ewing sarcoma patients have few treatment choices. In patients who have had a good performance status, VIT regimen may be considered for disease control.

Comparison of second-line treatments in metastatic renal cell carcinoma patients: A single-center experience.

Renal cell carcinoma is the 10th most common type of cancer, accounting for 3.7% of all cancers. Our study examines patients with metastatic renal cell carcinoma who received Axitinib or Nivolumab as second-line treatment. This study was designed as a retrospective analysis. Patients who received Axitinib or Nivolumab as second-line treatment for metastatic renal cell carcinoma at the Istanbul University Oncology Institute Medical Oncology outpatient clinic were included in the study. A total of 81 patients were included in the study, with a median follow-up period of 18.5 months (2-260 months). Of these patients, 29 (35.8%) received Axitinib as second-line treatment, while 52 (64.2%) received Nivolumab. The median duration of second-line treatment was 14 months (6-52) for Axitinib and 13.5 months (3-77) for Nivolumab. In our study, Nivolumab was found to have statistically better PFS and OS outcomes than Axitinib in male patients, patients diagnosed with metastatic disease, those with a favorable or intermediate International Metastatic Renal Cell Carcinoma Database Consortium risk score, patients diagnosed with metastatic disease or who developed metastasis within 12 months of diagnosis, those who developed metastasis ≥ 24 months after diagnosis, and patients with metastasis in a single organ. Both drugs are recommended as monotherapy for second-line and later treatments in the current NCCN guidelines for kidney cancers. Although there is no study in the literature showing that axitinib is more effective than nivolumab, nivolumab was found to be much more effective than axitinib in our study. Prospective studies with higher number of patients are needed on this subject.

Clinical course and features of soft tissue sarcomas in geriatric patients: a single-center experience.

OBJECTIVE: This study was performed to examine the disease course in geriatric patients with soft tissue sarcoma and determine the risk factors for mortality. METHODS: We retrospectively analyzed patients who were treated at Istanbul University Oncology Institute from January 2000 to August 2021. RESULTS: Eighty patients were included in the study. The patients' median age was 69 years (range, 65-88 years). The median overall survival of patients diagnosed between the ages of 65 and 74 years was 70 months, and that of patients diagnosed at the age of ≤75 years was significantly lower at 46 months. The median survival of patients who did and did not undergo surgical resection was 66 and 11 months, respectively, with a significant difference. The median overall survival of patients with positive and negative surgical margins was 58 and 96 months, respectively, also with a significant difference. Age at diagnosis and recurrence/metastasis significantly affected mortality. A 1-year increase in the age at diagnosis increased mortality by 1.147 times. CONCLUSION: Age of >75 years, inability to undergo surgery, positive surgical margins, and head and neck location may be associated with a poor prognosis in geriatric patients with soft tissue sarcoma.

Outcomes and prognostic factors in metastatic renal cell carcinoma patients with brain metastases.

BACKGROUND: To evaluate the outcomes and prognostic factors in patients with brain metastatic renal cell carcinoma (bmRCC). METHODS: The data of 322 patients with metastatic renal cell carcinoma, taken between 2012 and 2020, were retrospectively reviewed. Overall survival (OS) and prognostic factors were evaluated with Kaplan-Meier analysis and Cox regression analysis. RESULTS: Forty (12.4%) of the patients had bmRCC. Seventeen (42.5%) of the patients were de novo metastatic, and nine (22.5%) of the patients had brain metastases at presentation. Twenty-four (60%) patients previously had received various therapies (tyrosine kinase inhibitor or checkpoint inhibitors). After brain metastases developed, 35 (87.5%) of the patients received brain radiotherapy (whole-brain radiotherapy or stereotactic radiosurgery), and twenty-five (62.5%) patients received different systemic therapies. Nine patients received sunitinib, nine received pazopanib, five received nivolumab, and two received axitinib. The median OS was 8.8 months (range: 2.9-14.6) for all patients with bmRCC. In univariate analysis, the number of brain metastasis (P = 0.35), the site of brain metastasis (left, right or bilateral) (P = 0.79), the largest size of brain metastasis (P = 0.45), the number of extracranial metastatic sites (P = 0.81), de novo metastatic disease (P = 0.17), primary tumor site (left or right) (P = 0.90), and tumor grade (P = 0.09) were not statistically significant factors on OS. However, age (P = 0.02), a history of nephrectomy (P < 0.001), receiving brain radiotherapy (P = 0.005), and type of systemic treatment (P = 0.04) were statistically significant. Only, the effect of brain radiotherapy on OS (P = 0.01) was confirmed in multivariate analysis. CONCLUSIONS: In this study, we observed that the prognosis of patients with bmRCC was poor. Despite a small number of patients, we detected that the effect of tyrosine kinase inhibitors and nivolumab was comparable, and receiving brain radiotherapy was a prognostic factor for OS.

The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter real-world study from Turkey.

The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22-89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4-33.3) months, the median PFS and OS were 5.1 (95% CI: 3-7.3) and 18.1 (95% CI: 6.2-29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.

High-dose chemotherapy followed by autologous stem cell transplantation for adult patients With first relapse of Ewing's sarcoma: A single institution experience.

The prognosis of patients with Ewing's sarcoma family of tumors (ESFT) relapse is poor; the 5-year overall survival (OS) is 13%. We evaluated the effectivity of high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in adult patients with ESFT relapse. Between January 2010 and January 2021, we retrospectively analyzed 20 patients with ESFT who received HDT upon relapse. A combination of busulfan with melphalan was used as a conditioning regimen before ASCT. The median follow-up from diagnosis and from first relapse was 46.08 months (range; 10.71-186.87) and 14.41 months (range; 4.34-104.11), respectively. The median of age patients was 21.2 years (range, 17.6-25.3), and 10 (50%) patients were female. The tumor originated from the bone in 13 patients and soft tissue in 7 patients. Twelve patients had early (<2 years) relapse, and 8 patients had late (>2 years) relapse. Before HDT, 13 (65%) and 7 (35%) patients had pulmonary and extrapulmonary metastasis, respectively. After induction chemotherapy, 14 patients achieved complete response. The median OS1 and OS2 were 51.6 months (95% confidence interval [CI], range: 16.2-87) and 15.7 months (95% CI, range: 10.2-21.2), respectively. The 1-, 2-, and 5-year OS rates were 50%, 30%, and 15%, respectively. One patient died (sepsis) 1 month after ASCT. In univariate analyses, a disease-free interval (DFI) of < 2 years (P = .008) and incomplete response (P = .021) before ASCT were poor prognostic factors for OS2.HDT with ASCT can result in long-term survival of patients with ESFT relapse. HDT should be considered an important treatment opt ion in patients with a DFI > 2 years and complete response before transplantation.

Outcome of 177 Lu-PSMA Radionuclide Treatment in Advanced Prostate Cancer and Its Association With Clinical Parameters : A Single-Center Experience.

PURPOSE: This study was set out to analyze the efficacy and safety of 177 Lu-PSMA-617 (LuPSMA) treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS AND METHODS: Progressive mCRPC patients who received at least 1 cycle of LuPSMA therapy were evaluated retrospectively. Demographic, clinic, and histopathological data were documented. Treatment efficacy was determined based on biochemical response criteria (Prostate Cancer Clinical Trial Working Group 3), and toxicity rates were defined based on CTCAE v4.03. The prognostic significance of laboratory/clinical data and 68 Ga-PSMA PET/CT quantitative results were analyzed using SPSS Version 24.0. RESULTS: One hundred patients (median prostate-specific antigen [PSA] level, 75.7 ng/mL) who met the eligibility criteria were identified. The median number of cycles received per patient was 3 (range, 1-9). After the first cycles of LuPSMA, biochemical partial response, biochemical stable disease, and biochemical progressive disease were observed in 31%, 36%, and 33% of patients, respectively. Any PSA decline was determined in 60% of patients. After the fourth cycle of treatment, biochemical partial response, biochemical stable disease, and biochemical progressive disease were defined in 48%, 26%, and 26% of patients, respectively. The median overall survival (OS) from the first cycle of LuPSMA was 14 months. Patients who had any PSA response after the first cycle had significantly longer OS than nonresponders (median OS: 17 vs 9 months; P ≤ 0.001). Total PSMA-derived tumor volume ( P = 0.004), total PSMA activity per lesion ( P = 0.01), PSA ( P = 0.007), alkaline phosphatase ( P = 0.002), lactate dehydrogenase ( P < 0.001), and hemoglobin ( P < 0.001) were significant prognostic factors for OS in univariate Cox regression analysis. CONCLUSIONS: LuPSMA therapy is a favorable treatment for mCRPC with remarkable therapeutic efficacy and low toxicity rates, even in progressive disease under standard therapies. Baseline PSMA-based tumor burden, PSA, alkaline phosphatase, lactate dehydrogenase, and hemoglobin were significant predictors of OS and can be useful for selection of the best candidate for LuPSMA therapy.

The first case of primary testicular germ cell tumor containing nephroblastoma as the only one non-germ cell component.

Adult extrarenal nephroblastomas (Wilms' tumor) are extremely rare tumors. They show a higher incidence of non-seminomatous elements and these so-called 'teratoid' Wilms' tumors are suggested to be of germ cell origin. To date, however, the number of reported cases with gonadal teratoma containing nephroblastoma is very low, and due to this reason, there are no standardized criteria for the categorization and treatment of these lesions. To our knowledge, the first case of nephroblastoma arising in a non-atrophic testis has been reported and it is associated with a teratoma as morphologically identifiable germ cell tumor and rhabdomyosarcoma as a second non-germ cell element. We report the second case of an adult nephroblastoma that arose within the primary testicular teratoma in a non-atrophic testis. Teratoma and nephroblastoma within the same testis may have an important point to clarify the developmental mechanism in nephroblastomatous differentiation of germ cell tumors.

Response rates and adverse effects of continuous once-daily sunitinib in patients with advanced renal cell carcinoma: a single-center study in Turkey.

OBJECTIVE: Therapy targeted against the vascular endothelial growth factor pathway is a standard of care for patients with metastatic renal cell carcinoma. This study assessed the response rates and toxicity profiles of sunitinib on a continuous once-daily dosing regimen in Turkish patients with metastatic renal cell carcinoma. METHODS: Between April 2006 and August 2010, 74 patients with metastatic renal cell carcinoma who received sunitinib on a continuous, once-daily dosing regimen were included. Sunitinib was administered daily at a dose of either 37.5 mg (94% of the patients) or 25 mg (6% of the patients), without interruption, either as a second-line treatment after interferon-α or as a first-line treatment. Response, toxicity, progression-free survival and overall survival were evaluated. RESULTS: Of the 74 patients, 65 (88%) were diagnosed with clear cell renal cell carcinoma. The median treatment duration was 10 months (range, 2-42 months). The most common treatment-related adverse events were fatigue (75%), stomatitis (51%) and hypertension (50%). The most common Grade 3 or 4 adverse events were anemia (10%) and hand-foot syndrome (7%). Dose reductions were required in 50% of the patients, and early treatment discontinuation was necessary in 16% of the patients. Cardiovascular events were the most common adverse events that resulted in drug discontinuation. The objective response rate and the disease control rate were 30 and 78%, respectively. The median progression-free survival and overall survival were 13 and 25 months, respectively. CONCLUSIONS: Continuous, once-daily administration of sunitinib was generally well tolerated in Turkish patients with advanced renal cell carcinoma in a daily practice setting. This study's response rates were comparable to those in previous randomized trials.

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 cisplatinbased 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.

Optic disc and choroidal metastasis from sporadic medullary thyroid carcinoma: case report and review of the literature.

BACKGROUND: Choroidal metastasis is a very rare clinical manifestation of thyroid cancer. Herein, we report on a patient with non-familial medullary thyroid carcinoma (MTC), who presented with choroidal metastasis. CASE REPORT: A 63-year-old male patient with MTC presented with sudden loss of vision in his right eye for 1 month. The patient had a history of complete thyroidectomy and chemotherapy for disseminated MTC. Ophthalmological examination showed optic disc and choroidal metastases in the right eye and a small choroidal metastasis in the left eye. The patient was scheduled for external irradiation therapy for the ocular area but died 2 months after choroidal metastasis was diagnosed. CONCLUSIONS: Choroidal metastasis must be considered in MTC patients who develop loss of vision. This is a very rare clinical situation that generally occurs in the late advanced stages of the disease and carries a poor prognosis for these patients.

225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer: A Single-Center Experience.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted therapies are among the current promising treatments. We present our preliminary results on the use of 225Ac-PSMA therapy in patients with metastatic castration-resistant prostate cancer as a single center. METHODS: Twelve advanced stage metastatic castration-resistant prostate cancer patients who received 225Ac-PSMA therapy were recruited in this retrospective study. Patients were treated with 225Ac-PSMA therapy every 8 weeks, and prostate-specific antigen (PSA) response was analyzed. Meanwhile, overall survival (OS) and progression-free survival (PFS) were estimated. Hematological and nonhematological adverse effects were recorded before and at 8 weeks after the last treatment cycle. RESULTS: In total, 25 cycles of 225Ac-PSMA were administered to 12 patients. The pretreatment median PSA level was 129 ng/mL. After the first cycle of therapy, any PSA response was observed in 9 of 12 patients, whereas 6 of them had biochemical response of >50%. Four of 12 patients reached the best PSA response after the first treatment cycle, whereas 3 patients after the second and 2 patients after the third cycle. The median PFS and OS were 4 and 10 months, respectively. For patients with any PSA response after the first cycle, OS was found to be higher despite without any statistical significance (10 vs 4 months; P = 0.301) when compared with the nonresponsive group. No significant difference was encountered in terms of adverse effect in the pretreatment and posttreatment era. CONCLUSIONS: Our preliminary results are encouraging, especially patients who had PSA response after the first cycle of 225Ac-PSMA therapy.