V1 Bronwen 声望 1 生物安全 2021-08-20 22:28:11 上传
PACMEL: A phase 1 dose escalation trial of trametinib (GSK1120212) in combination with paclitaxel
Abstract Background We sought to determine the maximal tolerated dose of the MEK inhibitor trametinib with weekly paclitaxel, with a view to exploring the combination’s activity in melanoma lacking a BRAF V600 mutation. Methods In this phase 1 study we used a fixed dose of paclitaxel (80 mg/m2 intravenous (IV) on days 1, 8 and 15 of each 4 week cycle) and escalated the dose of trametinib (to a maximum 2 mg orally (PO) daily), following a 3 + 3 design. Eligible patients had advanced melanoma and could have received up to two previous lines of treatment for metastatic disease. Findings 15 patients were enrolled, all but one of whose melanoma was wild type for BRAF at codon 600. The maximal monotherapy dose of trametinib proved tolerable with weekly paclitaxel. The most frequent adverse events observed were rash and fatigue. Six (40%) partial responses were reported, including four of eight patients with NRAS mutations. Median progression free survival was 5.5 months (95% confidence interval (CI) 1.8–7.8 months) and overall survival, 14.1 months (95% CI 4.6–not reached). Interpretation Trametinib can safely be given with weekly paclitaxel at the full monotherapy dose. In this small group promising progression free and overall survival were observed in patients with melanoma lacking a V600 BRAF mutation.
V2 听说 声望 10 2021-08-20 18:07:24 上传
Use of complementary and alternative medicine: A multicenter cross-sectional study in 1089 melanoma patients
Abstract Background About half of patients with cancer use complementary and alternative medicine (CAM). So far, data on melanoma patients are missing. Objective The aim of our study was to evaluate the prevalence and predictors for the use of CAM in this patient group. Methods All patients with melanoma being attended at one of 7 skin cancer centres in Germany between March 2012 and March 2013 were invited to take part in a survey using a structured questionnaire on CAM. The physicians filled in a second part on the diagnosis, state and former and current therapy. Results Nearly half of the 1089 participants (41.0%) used CAM and half of those using CAM (56.8%) marked that this made them feel better. Biological-based CAMs which consists of substances taken were used by 25.9% of all patients (63.1% of those using CAM). Predictors of CAM use were education, psychological support, interest in CAM and previous CAM use. CAM users show higher physical activity, more often use psychosocial help and have contact with a self-help group. Family and friends (41.0%) as well as print media (41.7%) are the main sources of information. Most important reasons to use CAM are to strengthen one's own forces (57.7%) or the immune system (63.4%) and to be able to do something for oneself (53.7%). Conclusion Communication on CAM should become a regular topic in counselling melanoma patients. To increase safety, patients and physicians must have access to evidence-based information on these methods and their interactions with modern cancer treatments.
V3 假装 声望 42 2021-08-20 05:15:04 上传
Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual
To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent”; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472-492. © 2017 American Cancer Society.
V3 假装 声望 42 2021-08-19 23:19:44 上传
Hodgkin lymphoma: A review and update on recent progress
Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced-stage disease, HL is highly curable with combination chemotherapy, radiation, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody-drug conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death-1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced-intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long-term treatment toxicities.
V5 洱海没有海 声望 78 化学 2021-08-19 21:06:31 上传
High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis
Abstract Aim Immunotherapy in cancer is a recent and very promising approach, namely the inhibition of the PD/programmed death-ligand 1 (PD-L1) axis. Here we aimed to investigate the prognostic value of a soluble form of PD-L1 in hepatocellular carcinoma (HCC) patients. Methods HCC patients were prospectively recruited and soluble programmed death-ligand 1 (sPD-L1) levels were determined. sPD-L1 levels were compared to stages of cirrhosis and HCC. The association of the sPD-L1 levels and overall survival (OS) was assessed. Results Two hundred fifteen patients with HCC were prospectively included. The median serum sPD-L1 concentration in patients with HCC was 0.5 ng/ml (range 0.03–6.04). Soluble PD-L1 levels positively correlated with the stage of cirrhosis and with stages of HCC. Furthermore, sPD-L1 correlated positively with a marker of macrophage activation (sCD163) and inflammation (C-reactive protein). The cut-off for high-level sPD-L1 (>0.8 ng/ml) was defined by sPD-L1 levels determined in a healthy control cohort. Patients with high serum sPD-L1 concentrations had an increased mortality risk (hazard ratio 3.340, 95 % confidence interval 1.609–6.934, P < 0.001), while very low PD-L1 levels seem to come along with better prognosis. High sPD-L1 levels were associated with mortality independently from cirrhosis stage, alpha-fetoprotein and sCD163 levels in a multivariate Cox regression model. Conclusions We conclude that a high sPD-L1 level is a possible prognostic indicator for a poor outcome in HCC patients. The predictive value of sPD-L1 levels for a successful anti-PD1/PD-L1 therapy should be investigated in the future.
V4 咀嚼zer 声望 68 2021-08-19 19:51:00 上传
Most Gleason 8 Biopsies are Downgraded at Prostatectomy—Does 4 + 4 = 7?
Purpose Nonrepresentative biopsy sampling of prostate cancers with a biopsy Gleason score of 8 can adversely influence decisions regarding androgen deprivation in men receiving primary radiation therapy. The frequency of and factors associated with downgrading Gleason 8 biopsies at prostatectomy are not well known. Materials and Methods We used records from NCDB (National Cancer Database), a hospital based registry in the United States, of 72,556 men with prostate cancer diagnosed from 2010 to 2013, including 5,474 with Gleason 8 biopsies and no other high progression risk criteria according to NCCN (National Comprehensive Cancer Network®) Guidelines®. The prevalence of Gleason 8 downgrading was calculated. Generalized estimating equation multivariable regression models were used to estimate the prevalence ratios and 95% CIs of downgrading by demographic and clinical factors, and evaluate the association of Gleason 8 downgrading with cT (clinical T) to pathological T category up staging. Results Of 5,474 Gleason 8 biopsies in men lacking other high progression risk criteria 3,263 (60%) were downgraded, changing the progression risk category from high to intermediate. A higher prevalence of Gleason 8 downgrading was significantly and independently associated with decreasing age, African American race, lower cT category, lower prostate specific antigen quartile and certain combinations of primary and secondary Gleason grades (3 + 5 greater than 4 + 4 greater than 5 + 3). Gleason 8 downgrading in cases of cT less than 3 was independently and significantly associated with a lower prevalence of up staging (prevalence ratio = 0.65, 95% CI 0.61–0.69). Conclusions Downgrading Gleason 8 biopsies is common. Patient evaluation based on Gleason 8 biopsies often results in overestimating progression risk and disease extent, which may lead to overtreatment.
V4 卡迪夫 声望 43 热能与动力工程 2021-08-19 18:31:47 上传
Rectal Ulcers and Rectoprostatic Fistulas after 125I Low Dose Rate Prostate Brachytherapy
Purpose Radiation induced rectal ulcers and fistulas are rare but significant complications of low dose rate prostate brachytherapy for localized prostate cancer. We describe the incidence of ulcers and fistulas, and associated risk factors. Materials and Methods We reviewed the records of 4,690 patients with localized prostate cancer who were treated with low dose rate 125I prostate brachytherapy to a dose of 144 Gy with or without 6 months of androgen deprivation therapy. Patient, disease, comorbidity, treatment, dosimetric and posttreatment intervention factors were analyzed for an association with ulcer or fistula formation. Results At a median followup of 53 months 21 cases were identified, including 15 rectal ulcer cases, of which 6 progressed to fistulas, and an additional 6 cases of fistulas with no prior documented ulcers. Overall 9 rectal ulcer cases (0.19%) and 12 fistula cases (0.26%) were identified. In 8 of 15 patients ulcers healed with conservative management. No fistulas healed without surgical management. Two patients with fistulas died. Eight patients diagnosed with rectal ulcers subsequently underwent rectal biopsies, after which fistulas developed in 3. One patient with a de novo fistula underwent a preceding biopsy. Urinary interventions such as transurethral resection of the prostate were performed after brachytherapy in 5 of 12 patients with fistulas compared to 0 of 9 with ulcers alone. Argon plasma coagulation of the rectum for hematochezia was performed after brachytherapy in 3 of 12 patients with fistulas. Conclusions Rates of post-brachytherapy rectal ulcers and fistulas are low as previously described. Post-brachytherapy interventions such as rectal biopsy, argon coagulation and urinary intervention may increase the risk of fistulas.
V4 海绵宝宝520 声望 56 生物系 2021-08-19 17:54:22 上传
Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival
Abstract Background We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. Patients and methods We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes. Results A median of 2 (range: 0–10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis. Conclusion These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.
V2 范春嫦 声望 1 动植物检疫 2021-08-19 15:44:36 上传
Sofosbuvir and Ribavirin for Treatment of Compensated Recurrent Hepatitis C Virus Infection After Liver Transplantation
Background & Aims Interferon alfa–based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection. Methods In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary end point was sustained virologic response 12 weeks after treatment. Results Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. Sustained virologic response 12 weeks after treatment was achieved by 28 of 40 patients (70%; 90% confidence interval: 56%−82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported. Conclusions Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well-tolerated interferon-free treatment for post-transplantation HCV infection. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.
V2 暖先森 声望 7 动物生物技术 2021-08-19 11:23:22 上传
Health Related Quality of Life Following Radical Cystectomy: Comparative Analysis from the Medicare Health Outcomes Survey
Purpose Health related quality of life after radical cystectomy and ileal conduit is not well quantified at the population level. We evaluated health related quality of life in patients with bladder cancer compared with noncancer controls and patients with colorectal cancer using data from SEER (Surveillance, Epidemiology and End Results)-MHOS (Medicare Health Outcomes Survey). Materials and Methods SEER-MHOS data from 1998 to 2013 were used to identify patients with bladder cancer and those with colorectal cancer who underwent extirpative surgery with ileal conduit or colostomy creation, respectively. A total of 166 patients with bladder cancer treated with radical cystectomy were propensity matched 1:5 to 830 noncancer controls and compared with 154 patients with colorectal cancer. Differences in Mental and Physical Component Summary scores as well as component subscores were determined between patients with bladder cancer, patients with colorectal cancer and noncancer controls. Results SEER-MHOS patients were more commonly male and white with a mean ± SD age of 77 ± 6 years. Patients treated with radical cystectomy had significantly lower Physical Component Summary scores, select physical subscale scores and all mental subscale scores compared with noncancer controls. These findings were similar in the subset of 40 patients treated with radical cystectomy who had available preoperative and postoperative survey data. Global Mental Component Summary scores did not differ significantly between the groups. No significant differences were observed in global Mental Component Summary, Physical Component Summary or subscale scores between patients with bladder cancer and patients with colorectal cancer. Conclusions Patients with bladder cancer who undergo radical cystectomy have significant declines in multiple components of physical and mental health related quality of life vs noncancer controls, which mirror those of patients with colorectal cancer. Further longitudinal study is required to better codify the effectors of poor health related quality of life after radical cystectomy to improve patient expectations and outcomes.