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Induction chemotherapy with docetaxel and cisplatin is highly effective for locally advanced nasopharyngeal carcinoma

Radiotherapy (RT) with concomitant chemotherapy (CT) has improved the therapeutic outcome of patients with locally advanced nasopharyngeal carcinoma (LANC). However, the importance of induction CT before definitive therapy is still undefined. Patients (n=59) who had LANC were included in this retrospective study. They received induction CT consisting of cisplatin and docetaxel followed by definitive RT with cisplatin. The median age was 49 years (18-68). All patients were of stages II (15%), III (63%) and IV (22%). Fifty eight patients could receive 3 cycles of CT. Except one patient, there was no grade 3 or 4 toxicity during induction CT. Chemoradiotherapy could be given to 49 patients (83%). Twelve percent of patients had complete response after induction CT and this number had increased to 95% after the completion of the therapy. Objective responses (complete and partial) were 100% after the completion of the therapy. Median follow up time was 29 months. Nine patients had relapse (2 had local only, 4 distant, 3 local and distant). Three patients who had both local and distant relapse died during follow-up. Three year overall and progression free survival rates were 94.9% and 84.7%, respectively. Induction CT with docetaxel and cisplatin is a feasible and tolerable treatment for patients with LANC.

Noncutaneous Melanoma Have Distinct Features from Each Other and Cutaneous Melanoma

Objective: Compared to the cutaneous melanoma, noncutaneous melanomas are relatively rare and have a distinct pattern of behavior. We performed this study to define the clinical characteristics and outcomes of patients with noncutaneous melanomas and emphasize how they differ from cutaneous melanomas. Methods: 216 patients who were diagnosed with noncutaneous melanoma were assessed and their medical records between 2000 and 2010 were retrieved from the cancer registry. 475 patients with cutaneous melanoma were used for comparison. Results: Of the 216 noncutaneous melanoma patients, 83 had mucosal melanoma, 101 had ocular melanoma and 32 had unknown primaries. For mucosal melanoma, the head and neck was the most common anatomic site (53%), followed by the gastrointestinal tract (37%), female genital (6%) and urinary tract (4%). The majority of the ocular melanomas (94%) originated in the uvea. 32 patients demonstrated a primary unknown disease with regional metastasis as the dominant behavior (72%). Age was found to be statistically significantly different among melanoma patients (p < 0.001). Younger patients had more cutaneous and unknown primary melanomas, whereas older patients had more ocular and mucosal melanoma. In subset analyses, we found significant differences between cutaneous and ocular (p = 0.038) or mucosal (p < 0.001) melanomas. The ratios of metastasis on admission were higher in patients with mucosal (27.7%) and unknown primary (28.1%) melanomas, and lower for ocular (3%) melanomas (p < 0.001). Patients with cutaneous melanoma had an intermediate (12%) ratio. Patients with ocular melanoma had better outcome than patients with other melanoma sites (p < 0.05). While overall survival for cutaneous melanoma was significantly negatively correlated with male gender (p < 0.001), advanced stages (p < 0.001) and old age (p = 0.005), stage IV disease was the only independent prognostic factor in patients with ocular melanoma (p = 0.006). No prognostic factor for outcome was found for either mucosal or unknown primary melanomas. Conclusion: The clinical presentations and prognoses of different primary sites of melanoma are distinctive. Therefore, approaches to these melanomas should be different.

Abundant circulating microRNAs in breast cancer patients fluctuate considerably during neoadjuvant chemotherapy

Previous studies have revealed the aberrant expression of a number of microRNAs (miRNA/miRs) in the blood circulation of patients with breast cancer (BC). The aim of the present study was to assess the effect of neoadjuvant chemotherapy on the levels of a panel of BC-associated miRNAs, which are at relatively low (let-7, miR-10b, miR-34, miR-155, miR-200c and miR-205) or abundant (miR-21, miR-195 and miR-221) levels in the circulation. Patients with primary operable or locally advanced BC were enrolled in the study. The plasma levels of the miRNAs at baseline and at the fourth cycle of treatment were compared. Patients with stage II disease exhibited higher basal miRNAs levels than those with higher stages. The difference was most evident for miR-155 and miR-21 (P=0.05). From the initial to the fourth cycle of chemotherapy, the miRNA levels changed substantially. In samples in which the miRNA levels generally declined, a marked decrease (≤15,500-fold) was evident for the abundant miRNAs. Notably, the occurrence of a decrease in miRNA levels was more frequent in patients with smaller tumor sizes (P<0.05 for miR-21 and miR-195). This proof-of-concept study provides evidence that highly expressed miRNAs are affected most frequently by chemotherapy, particularly in patients with early stage tumors. This information may be valuable in assessing the response of the patients to therapy.

Prognostic factors in metastatic pancreatic cancer: Older patients are associated with reduced overall survival

Pancreatic cancer is a major health concern worldwide and, despite the attempts at management, the prognosis of patients with metastatic pancreatic cancer remains poor, with a median survival of a few months. The aim of this study was to identify and evaluate clinicopathological factors and elucidate the clinical significance of patient age for the outcome of metastatic pancreatic cancer. Data from a total of 154 metastatic patients with a histologically confirmed diagnosis of pancreatic cancer, who were treated and followed-up in our clinic, were recorded from medical charts. The patient sample included 102 (66%) males with a median age of 58 years (range, 25–88 years). The majority of the patients had a poor performance status (64%), weight loss of >10% body weight (74%), tumor size of >3 cm (75%) and elevated tumor markers, including carcinoembryonic antigen (CEA) (66%) and carbohydrate antigen 19-9 (CA19-9) (85%). The distributions of prognostic factors depending on patient age were largely identical. The median survival time of patients with metastatic disease was 179 days and the 1-year survival rate was 7%. The median survival time of elderly patients was significantly lower compared to younger patients (148 vs. 198 days, respectively; P=0.039). The 1-year survival rates in elderly and younger patients were 3 and 10%, respectively. In the univariate and multivariate analyses, elderly patients had poorer outcomes compared with younger patients (P=0.04 and 0.05, respectively). In all patients, the univariate analysis demonstrated that similar prognostic factors, including the performance status of the patients and tumor markers, such as serum CEA and CA19-9 levels, were associated with survival. In the multivariate analysis, younger patients with a poor performance status had a significantly shorter overall survival compared to those with a good performance status (P=0.008). However, no significant prognostic factor affecting the outcome was identified in the elderly patients. In conclusion, patient age is a major prognostic factor affecting the survival of patients with metastatic pancreatic cancer and elderly patients without poor prognostic factors may be eligible for the available treatment options.

Clinical and prognostic significance of coagulation assays in advanced epithelial ovarian cancer.

Objective Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological tumors and usually diagnosed at advanced stage. We aimed to identify the clinical and prognostic relevance of coagulation tests and their correlation with serum CA-125 levels in advanced EOC. Materials and Methods A total of 33 advanced-stage (stages III and IV) EOC patients were enrolled in the study. Of these patients, 17 had received neoadjuvant chemotherapy and 16 patients received chemotherapy after optimal debulking surgery. Several clinicopathologic factors, coagulation assays, routine biochemistry tests, and serum CA-125 levels were evaluated before treatment and compared with healthy subjects. Results All coagulation tests including prothrombin time (PT), activated partial thromboplastin time, international normalized ratio, fibrinogen, D-dimer, and platelet revealed statistically significant difference between patients and control subjects (P ⩽ 0.001). Elevated CA-125 levels were correlated with higher D-dimer values (P = 0.03). Prolonged PT was associated with poorer both overall (P = 0.03) and progression-free survival rates (P = 0.04). Conclusions Correlation of CA-125 with D-dimer is supposed to reflect hyperactivation of fibrinolytic pathway in the presence of a higher tumor load. Alterations in coagulation pathway reflected by prolonged PT support prognostic effects on survival of advanced-stage EOC patients.

Mucosal Melanoma in the Head and Neck Region: Different Clinical Features and Same Outcome to Cutaneous Melanoma

Mucosal melanoma (MM) in the head and neck (H&N) is relatively rare and behaves in distinct pattern from cutaneous melanoma (CM). We performed this study to define clinical characteristics and outcomes of patients and emphasize MM differences from CM. Forty-one patients with MM located in H&N were assessed. 94 CM patients originated from H&N region were also used for comparison. Patients had oral cavity (51%) and sinonasal location (49%).The median age was 60 years and gender distribution was equal. Thirty-two (78%) patients had localized stage, four (10%) patients had regional lymph node metastasis, and five (12%) patients had distant metastasis. The 1- and 5-year overall survival rates were 81% and 58%, respectively. Outcomes were similar between sinonasal and oral cavity patients (P = 0.67). Advanced disease was the significant prognostic factor for outcome (P = 0.03). MM patients are older (P = 0.008) and more diagnosed as a localized disease patients at presentation than those with CM (P = 0.06). Overall survival rates were identical in patients with MM and CM (P = 0.53). In conclusion, despite different clinical features, outcome was identical in patients with MM and CM located in the H&N region.

Clinical and Pathological Features of Breast Cancer Associated with the Pathological Complete Response to Anthracycline-Based Neoadjuvant Chemotherapy

Objective: Patients with breast cancer with a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a better prognosis than patients with residual disease. The aim of the current study was to identify predictors of pCR. Methods: This retrospective study included 388 patients treated with anthracycline-based NAC. Clinicopathological parameters were compared between the patients with and without pCR in breast and axilla. Results: Treatment consisted of FAC/FEC in 230 patients (59%), TAC in 39 (10%) patients and AC followed by docetaxel in 119 (31%). In all, 36 (9.3%) patients had pCR. In univariate analysis, age, tumor size, lymph node involvement, tumor grade (p = 0.077, n = 265), ER and HER-2 status (n = 213), lymphovascular invasion (LVI), type of chemotherapy and taxane-containing chemotherapy were associated with pCR. In multivariate analysis, ER negativity (p = 0.003), the absence of LVI (p = 0.009) and taxane-containing NAC (p = 0.026) were found to be significant indicators of pCR. Median follow-up time was 69 months. Progression-free survival was significantly improved in patients achieving pCR (p = 0.001). Conclusions: pCR is associated with a better outcome regardless of clinical and pathological parameters in breast cancer patients who receive NAC. The probability of pCR was higher in ER-negative, LVI-negative tumors and in patients treated with sequential taxane-containing chemotherapy.

Predictive value of marker half-life in relapsed and nonrelapsed nonseminomatous germ cell testicular tumor patients undergoing chemotherapy.

BackgroundThe aim of this study was to investigate the influence of a marker half-life (MHL) on relapse in nonseminomatous germ cell testicular tumor patients. MethodsMHL was retrospectively analyzed in relapsed (n = 37) and nonrelapsed patients (n = 28) undergoing first-line chemotherapy (CT). Before CT and after the second cycle of CT, serum &agr;-fetoprotein (AFP) and &bgr;-human chorionic gonadotropin levels were measured for MHL analysis. The International Germ Cell Cancer Collaborative Group risk classification system was used to assess the correlation between MHL and relapse. MHL was calculated according to a logarithmic formula. ResultsMedian follow-up was 25 months (range, 6 to 96 mo). A statistically significant difference was not observed between initial AFP (P = 0.266) and &bgr;-human chorionic gonadotropin (P=0.092) in both patient groups. MHL was statistically different between the relapsed and nonrelapsed patients with a good, intermediate, and poor prognosis, except for the half-life of AFP in patients with a poor prognosis. ConclusionsMHL is an indicator that predicted recurrence. Patients with an MHL longer than expected should be investigated to improve the effectiveness of treatment and should be treated with a recovery regimen.

Adrenocortical Carcinoma: Clinicopathological Features, Prognostic Factors and Outcome

Objective: The purpose of this study was to investigate the clinicopathological characteristics and treatment outcomes of patients with adrenocortical carcinoma (AC). Methods: Twenty-four patients (10 females and 14 males) diagnosed with AC between 1998 and 2009 were evaluated. Clinical features and outcomes were reviewed. Results: Median age was 46.5 years. One (4%) patient was classified as stage I, 10 (42%) were classified as stage II, 8 (33%) were classified as stage III and 5 (21%) were classified as stage IV. Tumor sizes ranged from 3 to 22 cm with a mean diameter of 11 cm. Five patients were locally inoperable at initial diagnosis. In addition to surgery, 2 of 19 patients were treated with an adjuvant cisplatin plus etoposide regimen. Sixteen patients were treated with chemotherapy after recurrence. Median survival time was 18 months. The 1- and 5-year overall survival estimates were 73 and 48%, respectively. Mean survival times for male and female patients were 58 and 12 months, respectively (p = 0.046). Early T stage (p = 0.04), lymph node negativity (p < 0.001), the absence of distant metastases (p < 0.001) and early stage (p < 0.001) were correlated with overall survival. Conclusion: AC is a rare disease with a poor prognosis. There are correlations between gender, stage and survival.

Predictive role of midtreatment changes in survivin, GSTP1, and topoisomerase 2α expressions for pathologic complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Introduction:The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2&agr; (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy. Methods:This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples. Results:The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01). Conclusions:Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.