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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Y90 selective internal radiation therapy and peptide receptor radionuclide therapy for the treatment of metastatic neuroendocrine tumors: combination or not?

BACKGROUND: Peptide receptor radionuclide therapy and selective internal radiation therapy are effective radionuclide therapy modalities for unresectable metastatic neuroendocrine tumor patients that cannot be controlled with somatostatin analogs. The present study is intended to evaluate the therapeutic efficacy and toxicity of the combined therapy of selective internal radiation therapy and peptide receptor radionuclide therapy and stand-alone selective internal radiation therapy in patients with neuroendocrine tumor, a liver-dominant disease. METHODS: This cohort consists of 27 patients with metastatic neuroendocrine tumor and liver-dominant disease. They were grouped as the patients who were treated with selective internal radiation therapy for unresectable liver metastasis (n = 15) and the patients who received a combination of selective internal radiation therapy and peptide receptor radionuclide therapy (n = 12) for hepatic and extrahepatic metastasis. Treatment efficacy and treatment-associated toxicity were retrospectively assessed in both groups. RESULTS: The objective treatment response and stable disease were found in 13 patients (86.6%) in the selective internal radiation therapy group and eight patients (66.6%) in the selective internal radiation therapy + peptide receptor radionuclide therapy group. The median overall survival rate was found to be 34.9 months, in the selective internal radiation therapy group and 67.5 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.217). The median progression-free survival data was not reached, and the mean values of progression-free survival were 53.1 ± 9.9 months in the selective internal radiation therapy group, and 27.2 ± 5.9 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.561). Temporary lymphopenia was the most common side effect. Grade 1-2 hepatotoxicity was observed to be 6.6% in the selective internal radiation therapy group, while it was not observed in selective internal radiation therapy + peptide receptor radionuclide therapy group. CONCLUSIONS: In the neuroendocrine tumors with liver-dominant metastatic disease, personalized selective internal radiation therapy and peptide receptor radionuclide therapy and their combinations result in increased survival rates. Selective internal radiation therapy alone could be an effective treatment in patients with liver-limited and -dominant disease.

Middle East observational study in metastatic soft tissue sarcoma: an epidemiological study on the treatment patterns (MOON).

PURPOSE: Soft tissue sarcomas (STS) are a heterogeneous group of rare mesenchymal neoplasms, accounting for < 1% of all newly diagnosed malignancies. These tumors can occur in almost any anatomic site though they most frequently occur in the extremities. The objective of the study was to describe the epidemiology, treatment paradigm, and real-world outcomes in the clinical management of metastatic STS (mSTS) in the Middle East and North Africa (MEA) region. METHODS: MOON was an observational, multicenter, retrospective patient chart review study which included 200 patients with mSTS in the final analysis. The primary objective of the study is exploratory, so it is presented using descriptive statistics. RESULTS: At the time of presentation, 62.0% patients had metastatic disease, 27.5% had received only their primary diagnosis and 10.0% had experienced a local recurrence. The most frequent STS localizations were lower extremities (74%), trunk (28.5%) and upper extremities (10.5%). Primary tumor was staged as T2b in the majority (60%) of patients. Surgical treatment was performed most often for the primary disease, whereas radiation therapy and chemotherapy were predominantly administered with palliative intent. A total of 38 patients received treatment with pazopanib. Thirteen adverse events (AEs) were attributed to pazopanib in eight patients. CONCLUSION: Adult patients treated for STS have al most equal gender ratio and mostly are middle aged. The majority of patients have metastatic disease and disease progression, and half of the patients died from the disease during the period of evaluation. This study obtained real-life data on the clinical management of STS in MEA countries which could be shared with the medical community.

Prognostic factors for survival in metastatic renal cell carcinoma patients with brain metastases receiving targeted therapy.

BACKGROUND: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. PATIENTS AND METHODS: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. RESULTS: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy. CONCLUSIONS: The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.

22-year survival following radical nephrectomy and several metastasectomies in a case of renal cell carcinoma.

Renal cell carcinoma (RCC) is a common malignancy. Metastases can be seen both synchronously, at the time of diagnosis, and metachronously during follow-up. At the time of diagnosis, 23% of the patients have metastatic disease. and 25% of patients will develop metastasis during follow-up period after nephrectomy. Nearly 80% of them develop within the first 5 years. However late metastasis of RCC have been also reported within the postoperative 10 years in the literature. For metastatic lesions, if surgically feasible, metastasectomy, and targeted pharmaceutical agents have been recommended. However any randomized controlled study which aimed to determine treatment protocol in patients who develop multiple metastases has not been cited in the literature. Herein, we are presenting a case with renal cell carcinoma in whom within 22 years of follow-up after 10 years of survival multiple metastases in different organs were detected which were managed with surgical, and medical treatments. As far as we know, this case is the first patient with the longest survival whose non-pulmonary metastases had been treated with more than one surgical interventions.

Renal cell cancer: overview of the current therapeutic landscape.

INTRODUCTION: The last decade has witnessed dramatic improvements in the diagnosis, classification and treatment of renal cell cancer (RCC). Besides improvements in surgical techniques in early stages, introduction of novel targeted agents has resulted in improved outcomes in advanced RCC for which no effective treatment existed until recently. AREAS COVERED: This article reviews epidemiology, pathology and pathogenesis, diagnosis, clinical staging, prognostic factors and treatment modalities of early stage and advanced RCC. Expert commentary: Although treatment options are expanding rapidly, practicing physicians face considerable challenges in the decision-making process. Therapeutic agents may have unique side effects and unexpected drug interactions. RCC represents one of the major success stories of clinical oncology in recent years and the progress appears to be far from having reached a plateau. We aim to present a comprehensive in-depth review of RCC in an attempt to provide evidence-based recommendations and future perspectives for practicing oncologists.

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.

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.

Systemic Rituximab Immunotherapy in the Management of Primary Ocular Adnexal Lymphoma: Single Institution Experience.

PURPOSE: To evaluate the efficacy of systemic rituximab immunotherapy in the management of primary ocular adnexal lymphomas (OAL). MATERIALS AND METHODS: Clinical records of 10 consecutive patients (11 eyes) with biopsy-proven OAL managed with systemic anti-CD20 monoclonal antibody (rituximab; 375 mg/m(2) intravenously once every three weeks for 6-8 cycles) between June 2008-March 2013 were evaluated retrospectively. Orbital magnetic resonance imaging and positron emission tomography were performed to evaluate any orbital and systemic involvement, respectively. Clinical response was classified as complete or partial. RESULTS: The age of patients ranged between 27-85 (median, 55) years. Nine patients (90%) presented with unilateral and one (10%) with bilateral conjunctival involvement. Orbit was affected in 4 patients (40%), one of which had also choroidal involvement (10%). None of the patients had systemic involvement at initial presentation. All patients received an average of 7 cycles (range, 6-8) of systemic immunotherapy. After a median follow-up of 31 months (range, 10-61 months), complete response without recurrence could be achieved in 4 eyes (36%) with rituximab monotherapy. No systemic or ocular side effects were observed in any patient. Additional radiotherapy was required in 6 patients (7 eyes; 64%) with partial response or recurrence. CONCLUSIONS: Complete regression of primary OALs without recurrence was observed in about one-third of eyes after systemic rituximab monotherapy. Adjunctive radiotherapy was required in remaining two-thirds of the cases to achieve complete response. Thus, considering the balance between high rate of local control and potential ocular complications of radiotherapy, systemic rituximab can be considered as a first-line therapeutic option in the management of primary OAL.