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.

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.

The use of bevacizumab in primary malignant tumors of the central nervous system: A single-center experience.

Primary central nervous system tumors rank 8 among other cancers in patients over 40 years of age. Glioblastoma is the most common primary central nervous system malignancy, accounting for 48 percent of the cases. The present study evaluates the effect of bevacizumab on the disease course in patients who received bevacizumab therapy due to primary central nervous system tumors in our clinic. The study was designed as a retrospective study. The records of patients treated between January 2000 and August 2021 were reviewed and patients who received bevacizumab therapy due to primary central nervous system tumor were included in the study to evaluate the effect of the therapy on disease course among the subgroups of patients. The study included 70 patients. Of these patients, 40 were male (57.1%) and 30 (42.9%) were female. The median duration of follow-up was 28 months (8-209 months). The median age of the patients was 47 years. The median duration of exposure to bevacizumab was 5 months (1-33 months). Forty-nine patients (71.4%) were histologically diagnosed with glioblastoma multiforme. The median progression-free survival (PFS) was 5 months (95% confidence interval 4-6). The median overall survival (OS) was 8 months (95% confidence interval 6.97-9.02). No statistically significant difference in OS or PFS was observed in any patient subgroup. The therapy was discontinued only in 2 patients (2.9%) due to side effects (1 patient with pulmonary embolism and 1 patient with intracranial hemorrhage). The present study found that the use of bevacizumab is safe in terms of side effects. No statistically significant difference in OS or PFS was observed in any patient subgroup. There is a need for studies on a larger number of patients to find out which patient subgroup benefit the most from bevacizumab therapy.

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.

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.

A rare case of ruptured liver metastases from a laryngeal cancer.

Rupture of a metastatic liver tumor associated with laryngeal cancer is a very rare complication with no previous case in the literature. We present a case of ruptured liver metastases which was treated conservatively. Dynamic contrast-enhanced computed tomography demonstrated active extravasation and discontinuity of liver capsule. When the patient came to our hospital from the external medical center, we did not see active extravasation on control computed tomography. This case highlights the role of radiologic imaging in the diagnosis and follow-up of ruptured hepatic metastases.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

Safety of Fibroblast Activation Protein-Targeted Radionuclide Therapy by a Low-Dose Dosimetric Approach Using 177Lu-FAPI04.

OBJECTIVES: This study is set out to estimate the radiation-absorbed doses to normal organs and tumor tissue using low-dose 177Lu-FAPI04 dosimetry to determine the safety and theranostic potential of fibroblast activation protein-targeted radionuclide therapy. PATIENTS AND METHODS: Four patients with metastatic advanced-stage cancer were administered low-dose 177Lu-FAPI04 for dosimetry measurements. Data acquisition for dosimetry of normal organs and tumors was performed by whole-body and 3D SPECT/CT imaging at 4, 24, 48, and 96 hours after administering 177Lu-FAPI04. Blood samples were drawn at 5, 15, 30, 60, 60, 120, and 180 minutes, and at 24, 48, and 96 hours for bone marrow dosimetry calculations. RESULTS: Mean absorbed doses per megabecquerel were 0.25 ± 0.16 mGy (range, 0.11-0.47 mGy), 0.11 ± 0.08 mGy (range, 0.06-0.22 mGy), and 0.04 ± 0.002 mGy (range, 0.04-0.046 mGy) for kidneys, liver, and bone marrow, respectively. The respective maximum estimated amount of radioactivity to reach radiation-absorbed dose limits were 120.9 ± 68.6 GBq, 47.5 ± 2.8 GBq, 397.8 ± 217.1 GBq, and 52.4 ± 15.3 GBq for kidneys, bone marrow, liver, and total body. The mean absorbed dose per megabecquerel was 0.62 ± 0.55 mGy for bone metastases, 0.38 ± 0.22 mGy for metastatic lymph nodes, 0.33 ± 0.21 mGy for liver metastases, and 0.37 ± 0.29 for metastatic soft tissue. The maximum absorbed dose in a tumor lesion was 1.67 mGy/MBq for bone, 0.6 mGy/MBq for lymph node, 0.62 mGy/MBq for liver, and 1 mGy/MBq for soft tissue. CONCLUSIONS: The mean absorbed dose to organs at risk with 177Lu-FAPI04 is reasonably low, allowing for low tumor-absorbed dose rates by administering a higher dose. Further research on optimizing therapeutic efficacy and using alternative radioisotopes is necessary, along with an individualized dosimetric approach.

Can PSMA-based tumor burden predict response to docetaxel treatment in metastatic castration-resistant prostate cancer?

PURPOSE: We investigated the role of PSMA-derived tumor burden in predicting docetaxel (DTX) therapy response in metastatic castration-resistant prostate cancer (mCRPC). METHODS: Fifty-two mCRPC patients who received at least six cycles of DTX as the first-line treatment following 68Ga-PSMA PET/CT were enrolled in this retrospective study. Total PSMA-derived tumor volume (TV-PSMA) and total lesion PSMA activity (TL-PSMA) were derived from metastatic lesions. A ≥ 50% decline in PSA was defined as a response; a ≥ 25% increase in PSA was defined as progression. Univariate/multivariate logistic and cox regression analyses were performed to predict PSA response, OS, and TTP. RESULTS: Twelve (23%) patients had PSA progression after chemotherapy, while 40 patients (77%) achieved a PSA response. On univariate analysis, a significant association was found between TV-PSMA (p = 0.001), TL-PSMA (p = 0.001), pre-PSA (p = 0.012), LDH (p = 0.003), Hg (p = 0.035), and PSA response to DTX. High TV-PSMA (> 107 cm3) (p = 0.04) and high LDH (> 234 U/L) (p = 0.017) were 8.2 times and 12.2 times more likely for DTX failure in multivariate regression analyses. The median TTP was 16 months, and the median OS was not reached. Patients with high TV-PSMA (p = 0.017), high TL-PSMA (> 1013 cm3) (p = 0.042), high age (> 70 years) (p = 0.016), and high LDH (p ≤ 0.001) had significantly shorter OS, while only high TV-PSMA (p = 0.038) and high age (p = 0.006) were significantly related with shorter TTP. High TV-PSMA (p = 0.017) and high age (p = 0.01) were significant predictors for shorter OS, while only high age (p = 0.006) was a significant predictor for shorter TTP in multivariate analysis. CONCLUSION: Patients with high TV-PSMA had a significantly higher risk for DTX failure. PSMA-based tumor burden prior to DTX therapy seems to be a reliable predictive tool for survival in mCRPC patients.

177Lu-PSMA Therapy for Metastatic Testicular Mixed Germ Cell Tumor.

ABSTRACT: Prostate-specific membrane antigen (PSMA) overexpression in various tumors are demonstrated in both in vitro and in vivo studies. Prostate-specific membrane antigen-directed radionuclide therapies are generally used in prostate cancer and could be also useful in PSMA-avid other malignancies. Herein, we present a case of a 46-year-old male patient who had progressive metastatic testicular mixed germ cell tumor, despite repeated operations and treatments. 68Ga-PSMA PET/CT was performed to assess eligibility for 177Lu-PSMA therapy. Patient had intense PSMA uptake in metastatic lesions, and 177Lu-PSMA has been given to control of disease. However, α-fetoprotein level progressed, and mixed therapy response was detected in 68Ga-PSMA PET/CT.

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. OBJECTIVE: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. RESULTS AND LIMITATIONS: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. CONCLUSIONS: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. PATIENT SUMMARY: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.

The expression levels of miRNA-15a and miRNA-16-1 in circulating tumor cells of patients with diffuse large B-cell lymphoma.

MicroRNAs (miRNAs) have major roles in nearly all cellular process including gene expression, and may behave as oncogene or tumor suppressor gene by binding to complementary sequences in the target mRNA. The circulating microRNA-15a (miRNA-15a) and microRNA-16-1 (miRNA-16-1) of 15 healthy adults and of 40 untreated patients diagnosed with diffuse large B-cell lymphoma (DLBC) were recruited to investigate the expression levels. The expression levels of miRNA-15a, and miRNA-16-1 genes of the untreated DLBCL patients, and healthy individuals with matched age, sex and ethnicity were examined. MicroRNA expression profiles obtained from peripheral blood were investigated. The samples were collected from 40 patients diagnosed with DLBC patients, and from 15 healthy controls. Two miRNAs were selected, and expression profile was examined using a quantitative real-time polymerase chain reaction (qPCR) based on the previous studies. Statistically significant expression level differences (p < 0.05) were detected for miRNA-16-1 in DLBCL patients and healthy control groups. miRNA-16-1 gene expression level was found approximately ninefold higher in the patient group compared to the controls; however, no statistical difference was detected in the expression profile of miRNA-15a between the both groups. On the other hand, the decreased gene expression in miRNA16-1 was observed in 88.3% of DLBCL patients. These results suggested that there was no statistically significant decrease in the miRNA-15a gene expression in DLBCL patients (p > 0.05). On the contrary to the literature, miRNA-16-1 expression level was suppressed in DLBCL group in our study, however no whole gene silencing was performed. MicroRNA-16-1 might be suggested to behave as a tumor suppressor in DLBCL in our study.

Neoadjuvant sequential chemoradiotherapy versus radiotherapy alone for treatment of high-risk extremity soft tissue sarcoma: a single-institution experience.

AIM OF THE STUDY: Patients with large and high-grade extremity soft-tissue sarcoma are at significant risk for distant metastasis and sarcoma-related death. There is no randomized trial comparing chemoradiotherapy to radiotherapy in the neoadjuvant setting for high risk extremity soft-tissue sarcoma. The aim of this study is to evaluate the outcomes of patients treated with two different modalities (neoadjuvant sequential chemoradiotherapy vs. radiotherapy alone) in a single center. MATERIAL AND METHODS: Data of 67 patients were analyzed retrospectively. Thirty-four patients received neoadjuvant sequential chemoradiotherapy (2-3 cycles of doxorubicin (75 mg/m2) and ifosfamide (6 g/m2) followed by radiotherapy of 28 Grays (Gy) administered as 8 fractions of 35 Gy) and 33 patients received radiotherapy alone. R0 resection rates and 3-year survival estimates were evaluated. RESULTS: Median follow-up time was 37 months. The estimated 3-year overall and disease-free survival rates for the whole patient group were 79% (95% CI: 67.0-86.4) and 57.9% (95% CI: 46.3-69.0), respectively. The most common side effects were nausea and leucopenia. Three-year overall, disease-free, local recurrence-free and distant recurrence-free survival rates did not differ significantly. All patients except one underwent wide excision or compartmental resection. R0 resection rate for the whole patient group was 92.5% (n = 62). Sites of progression were similar across both treatment arms. CONCLUSIONS: Preoperative hypofractionated radiotherapy alone or sequentially with chemotherapy result in high rates of limb salvage and acceptable toxicity. Our study results did not show a statistically significant treatment effect regarding survival and patterns of failure.

Papillary Renal Cell Carcinoma Arising in a Lymph Node Metastasis of a Testicular Teratoma: A Very Rare Occurrence.

We present a case of a teratoma with somatic type malignancy (TSM) in the form of papillary renal cell carcinoma (pRCC) within supraclavicular and retroperitoneal lymph node metastases of a testicular pure teratoma. Resection of both masses revealed a teratoma without any other germ cell tumor component. A papillary carcinoma component was also detected intermingled with the teratomatous elements. The carcinoma cells displayed eosinophilic cytoplasm and prominent nucleoli. Groups of foamy histiocytes in the fibrovascular cores was a striking finding that brought pRCC to mind. Immunoreactivity for CK7, PAX8, AMACR, CD10, napsin, and vimentin along with morphologic findings confirmed renal cell differentiation. No radiological evidence of a primary renal cell carcinoma was found in the kidney. Consequently, pRCC arising in a teratoma was diagnosed. TSM is described as teratoma with a malignant component that is typically encountered in other organs and tissues. TSM in the form of pRCC is an extremely rare entity. Our case is the second example of a testicular germ cell tumor metastasis with a somatic malignancy in the form of pRCC. In conclusion, carcinomas of renal cell differentiation should be kept in mind as a rare form of TSM, especially in metastatic germ cell tumors.

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.

Sunitinib for patients with metastatic non-clear cell renal cell carcinoma: a Multicenter Retrospective Turkish Oncology Group trial.

AIM: This study aimed to assess the clinical efficacy and toxicity of sunitinib, a targeted-agent, for non-clear cell renal cell carcinoma. PATIENTS AND METHODS: Sixty-three patients with complete clinical data from 13 oncology Centers were retrospectively evaluated. Outcomes analyzed were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: The median age of all patients, 38 men (60.3%) and 25 women (39.7%), was 63 years (range=25-82 years). Histological subtypes included 46 (88%) cases of papillary RCC, 10 of chromophobe, and 7 unclassified cases. Median treatment duration was seven months (range=2-86 months). At the time of this analysis, 52 patients had discontinued treatment, 33 of whom had died. Treatment discontinuation was due to disease progression in 43 patients, and toxicity in nine. Dose interruption was necessary in 22 (34.9%) patients, and dose reduction in 27 (42.9%). The objective response rate and disease control rate were 11.1% and 63.5%, respectively. The median PFS and OS were 7.6 months (95% confidence interval (CI)=5.5-9.7 months) and 22.0 months (95% CI=13.4-30.6 months), respectively, with 1-year rates of 64.7% and 33.7%, respectively. CONCLUSION: Clinical outcome of the metastatic non-clear cell RCC patients with sunitinib treatment seemed to be worse than the historical data of clear cell RCC patients, in terms of PFS, OS and objective response. New and more effective targeted-therapies and better understanding of the underlying molecular processes are necessary to improve survival outcome for these patients.

Associations between clinicopathological prognostic factors and pAkt, pMAPK and topoisomerase II expression in breast cancer.

This study aimed to examine the associations between mitogen activated protein kinase (MAPK), Akt, and topoisomerase II expression and other well established clinical and pathological prognostic factors in patients with breast cancer. A total of 42 women with breast cancer who underwent anthracycline based chemotherapy were included in this retrospective study. Immunohistochemical methods were utilized to examine the expression of phosphorylated MAPK (pMAPK), phosphorylated Akt (pAkt), HER-2/neu and topoisomerase IIα (topo IIα) in tissue blocks. Subsequently, the associations between pMAPK, pAkt, and topoisomerase IIα (topo IIα) expression characteristics and disease stage (T and N), tumor grade, estrogen/progesteron receptor status, and HER-2/neu expression were explored. Median age of the patients was 63 years (range, 37-82). There was a significant association between N stage and topoisomerase IIα expression (P = 0.021), with increasing rates of positivity in higher grades: N0, 22.7%; N1, 11.1%; N2, 42.9%; N3, 100%. In addition, topo IIα expression was higher in estrogen receptor-positive versus estrogen receptor-negative tumors (50% vs. 0%, P = 0.0004) and MAPK expression was more frequent among progesteron receptor-positive versus negative tumors (64.0 versus 20.0%, P = 0.027). Our results show that the tissue expression of topo IIα and MAPK, which play a role in the intracellular signal pathways, is associated with certain established prognostic factors in breast cancer. Further studies examining survival rates and involving larger sample populations are warranted to better define the importance of the observed associations.

Survival and prognostic factors in adult patients with recurrent or refractory ewing sarcoma family tumours: a 13-years retrospective study in Turkey.

AIM: The aim of the present study was to evaluate the results of treatment and prognostic factors in adult patients with recurrent or refractory Ewing's sarcoma family tumors (ESFT). PATIENTS AND METHODS: We retrospectively evaluated treatment outcomes of 54 consecutive patients with ESFT (aged 15 years or more) with complete medical records, who were treated with multimodal therapies after recurrence at the Istanbul University, Institute of Oncology. RESULTS: The commonly used chemotherapy regimens at relapse were ifosfamide and etoposide (IE), ifosfamide and etoposide plus carboplatin (ICE), and oral etoposide. The median progression-free survival and overall survival for the entire group were 6.3 (95% confidence interval, 3.08-9.60) and 8.6 (95% confidence interval CI, 4.7-12.4) months, respectively. Multivariate analysis using a Cox proportional hazards model showed that non-IE/ICE chemotherapy regimens (p=0.003, hazard ratio=2.38) and the presence extrapulmonary metastases (p=0.045, hazard ratio=2.15) were associated with worse overall survival. CONCLUSION: In primary refractory or relapsed ESFT, the presence of extrapulmonary metastases and treatment with salvage regimens other than ifosfamide and etoposide and/or carboplatin correlate with a poor prognosis.

Biweekly triplet chemotherapy with gemcitabine, cisplatin and vinorelbine for advanced chemotherapy naïve non-small cell lung cancer.

AIMS AND BACKGROUND: To investigate the efficacy and tolerability of biweekly scheduled triplet chemotherapy consisting of gemcitabine, cisplatin and vinorelbine for chemotherapy-naïve advanced non-small cell lung cancer. METHODS AND STUDY DESIGN: Patients with stage IIIB/IV non-small cell lung cancer and performance status of 0-2 were eligible. Patients who had brain metastasis and of an older age were also enrolled in the study. The triplet combination chemotherapy consisted of gemcitabine, cisplatin and vinorelbine at the doses of 1000 mg/m(2), 25 mg/m(2) and 50 mg/m(2), respectively, were administered on day 1 and 14, every 28 days, up to 6 cycles. RESULTS: Thirty patients were enrolled in the study. Median age was 60 years (range, 42-74). Most of the patients (83%) had metastatic disease and 7 patients (23%) had brain metastasis. In assessing 24 patients for response evaluation, none had complete response. Partial responses were achieved in 18 (60%) patients. Four patients (13%) had stable disease and 2 (7%) progressed. Thirteen percent and 20% of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. Febrile neutropenia, severe thrombocytopenia, hepatic and renal toxicity were not seen. Overall and progression-free survival were 8.15 and 7.15 months, respectively. Patients who had no brain metastasis ( P = 0.069), who had more than 3 courses of chemotherapy (P <0.001), and who had chemotherapy applied without dose reduction (P = 0.018) had better survivals. CONCLUSIONS: The biweekly schedule of the triplet chemotherapy combination including gemcitabine, cisplatin and vinorelbine was effective in advanced, mostly metastatic non-small cell lung cancer with acceptable and manageable side effects.