Definitive external-beam radiotherapy versus radical prostatectomy in clinically localized high-risk prostate cancer: A retrospective study

PubMedID: 30611260Background: Optimal treatment of high-risk prostate cancer remains controversial. We aimed to compare treatment outcomes of prostate cancer patients treated with definitive external-beam radiotherapy (ExRT) or radical prostatectomy (RP). Methods: The records of 120 high-risk clinical stage T2b-T4 N0 M0 prostate cancer patients treated with definitive ExRT or RP were reviewed. Patients with pretreatment prostate-specific antigen (PSA) levels ?20 ng/mL or clinical ?T3 stage or Gleason score (GS) ?8 were included in the study. Biochemical failure free survival (BFFS), distant metastasis free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. Cox regression analysis was performed to determine predictors of BF. Results: Seventy-two patients received definitive ExRT with androgen-deprivation therapy in 95.8% and 48 patients underwent RP with pelvic lymph node dissection. Mean age (67.7 ± 6.6 vs 64.5 ± 7.6 year, p = 0.017) and the rate of patients with PSA levels ?20 ng/mL (69.4% vs 47.9%, p = 0.022) were higher in the definitive ExRT group than the RP group. Distributions of GS and clinical T stage were similar. Mean follow-up was 60.2 ± 30.3 months in the definitive ExRT group and 41.3 ± 21.5 months in the RP group (p < 0.001). Twenty-five % of the RP group received adjuvant ExRT and 41.7% received salvage ExRT. Biochemical failure was significantly higher (52.1% vs 21.4%, p < 0.001) and the mean BFFS was significantly lesser (34.4 ± 3.9 vs 97.8 ± 5.9 months, p < 0.001) in the RP group than the definitive ExRT group. However, DMFS, CSS and OS were similar in both groups. In multivariate analysis, being in the RP group significantly increased the risk of BF (p < 0.001). Furthermore, not receiving pelvic lymphatic irradiation in the definitive ExRT group (p = 0.048) and having positive surgical margin in the RP group (p = 0.050) increased the risk of BF. Conclusions: BF was significantly higher and the mean BFFS was significantly lesser in high-risk prostate cancer patients undergoing RP than definitive ExRT while DMFS, CSS and OS were similar in both treatment groups. © 2019 The Author(s)

Cutaneous melanoma in Turkey: Analysis of 1157 patients in the Melanoma Turkish Study

PubMed ID: 26416068Purpose: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma. Methods: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma. Results: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <lmm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients). Conclusion: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database

Cutaneous melanoma in Turkey: Analysis of 1157 patients in the Melanoma Turkish Study

PubMed ID: 26416068Purpose: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma. Methods: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma. Results: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <lmm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients). Conclusion: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database

Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: The single-arm, open-label REGARD study

Objectives Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC. Design Open-label, single-arm, phase IIIb study conducted between July 2013 and April 2015. Setting 11 tertiary centres in Turkey. Participants Eligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status <= 1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male. Interventions Patients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity. Primary and secondary outcome measures The primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints. Results The median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77\% had a grade >= 3 TEAE. The most common grade >= 3 regorafenib-related TEAEs were hypophosphataemia (11\%), fatigue (8\%), hyperbilirubinaemia (6\%), hand-foot skin reaction (5\%), hypertension (5\%), anorexia (5\%) and increased alanine aminotransferase (5\%). TEAEs led to dose reduction in 30\% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17\% of patients. Median PFS was 3.1 months (95\% CI 2.9 to 3.8). Conclusion The regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC

Utilização das vitaminas C e E em rações para frangos de corte mantidos em ambiente de alta temperatura Use of vitamins C and E on ration for broilers kept in high temperature environment

O experimento foi realizado para avaliar os efeitos da suplementação das vitaminas C ou E na ração sobre o desempenho, as características de carcaça e os parâmetros hematológicos de frangos de corte mantidos em ambiente de alta temperatura. Foram utilizados 450 frangos de corte distribuídos em delineamento inteiramente ao acaso, com cinco tratamentos, cada um com nove repetições de 10 aves (período 1 a 21 dias) ou de 7 aves (período de 22 a 42 dias) por unidade experimental. Os tratamentos foram: ração basal (RB) sem suplementação de vitaminas C e E; RB + 300 ppm de vitamina E; RB + 230 ppm de vitamina C; RB + 300 ppm de vitamina E + 230 ppm de vitamina C; e RB + 150 ppm de vitamina E + 115 ppm de vitamina C. Não houve efeito da suplementação das vitaminas C e E no desempenho zootécnico das aves na fase de 1 a 21 dias de idade. Na fase de 1 a 42 dias, a suplementação das vitaminas C e E influenciou somente a conversão alimentar. Os melhores resultados para os pesos absoluto e relativo de peito foram observados nas aves que receberam a ração basal suplementada com as combinações das vitaminas C e E. A concentração plasmática de triiodotironina, a porcentagem de células sanguíneas, a relação heterófilo/linfócito e os pesos absoluto e relativo do baço aos 21 e 42 dias de idade não foram influenciados pela suplementação vitamínica. A suplementação das vitaminas C e ou E não influi no desempenho zootécnico, no peso do baço e nos parâmetros sanguíneos de frangos de corte mantidos até 42 dias de idade em ambiente de alta temperatura. As combinações das vitaminas C e E promovem melhora nos pesos absoluto e relativo de peito de frangos de corte sob alta temperatura.<br>This experiment was carried out to evaluate the effect of supplementation of vitamins C or E in the diet on performance, carcass characteristics and hematological parameters of broilers kept under high environmental temperature. Four hundred and fifty broilers were distributed in a completely randomized design with five treatments and nine replications, with 10 and 7 birds per experimental unit, respectively, according to the periods from 1 to 21 and 22 to 42 days old. Treatments consisted of a basal diet (RB) without supplementation of vitamins C and E; RB + 300 ppm of vitamin E; RB + 230 ppm of vitamin C; RB + 300 ppm of vitamin E + 230 of vitamin C, and RB + 150 ppm of vitamin E + 115 of vitamin C. Treatments did not influence performance of birds in the phase of 1 to 21 days of age. At 1 to 42 days of age, supplementation of vitamins C and E only influenced feed conversion. The best results for the absolute and relative weights of breast were observed in birds fed the basal diet supplemented with different combinations of vitamins C and E. Plasma concentration of triiodothyronine, percentage of blood cells, the heterophil/lymphocyte ratio and absolute and relative weights of the spleen at 21 and 42 days of age were not influenced by vitamin supplementation. Supplementation of vitamins C and/or E did not influence performance, weight of the spleen or blood parameters of chickens maintained until 42 days of age in a high temperature environment. The combination of vitamins C and E promotes improvement in absolute and relative weights of breast of broilers reared under high temperatur

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Background: Ramucirumab—an IgG1 vascular endothelial growth factor receptor 2 antagonist—plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5–13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3–4·8] vs 2·8 months [2·6–2·9]; HR 0·696 [95% CI 0·573–0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9–11·4) in the ramucirumab group versus 7·9 months (7·0–9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724–1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding: Eli Lilly and Company. © 2020 Elsevier Lt