scholarly journals Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

2014 ◽  
Vol 1 (4) ◽  
pp. 166-171 ◽  
Author(s):  
Alba A. Brandes ◽  
Enrico Franceschi ◽  
Mario Ermani ◽  
Alicia Tosoni ◽  
Fiorenzo Albani ◽  
...  
Keyword(s):  
Methylation Status ◽  
High Volume ◽  
Population Based ◽  
Phase Iii ◽  
Treatment Center ◽  
Current Standard ◽  
Pattern Of Care ◽  
Phase Iii Trials ◽  
Emilia Romagna Region ◽  
High Volume Center

Abstract Background As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. Methods Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. Results Two hundred sixty-seven GBM patients (median age, 64 y; range, 29–84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2–12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0–18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248–0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388–0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328–0.986; P = .0446). Conclusions The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

A large prospective Italian population study (Project of Emilia-Romagna Region in Neuro-Oncology; PERNO) in newly diagnosed GBM patients (pts): Outcome analysis and correlations with MGMT methylation status in the elderly population.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2021-2021
Author(s):  
Enrico Franceschi ◽  
Alicia Tosoni ◽  
Luca Morandi ◽  
Serenella Cerasoli ◽  
Giovanni Lanza ◽  
...  
Keyword(s):  
Postoperative Radiotherapy ◽  
Methylation Status ◽  
Survival Rates ◽  
The Elderly ◽  
Population Based ◽  
Phase Iii ◽  
Outcome Analysis ◽  
Italian Population ◽  
Mgmt Methylation ◽  
Emilia Romagna Region

2021 Background: The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly pts with GBM remains unclear. We therefore evaluated the efficacy of this approach in pts >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. Methods: The criteria for selecting pts enrolled in the PERNO study were: age >70 years; PS 0-3; histologically confirmed GBM; postoperative radiotherapy after surgery; residence in the Emilia Romagna region. Data were collected prospectively. Results: Pts accrual, started on January 1 2009, was closed, as planned, on December 31 2010. In the pts enrolled (n=53), median overall survival (mOS) was 11.1 months (95% CI: 8.8 - 13.5); survival rates at 1-, 2- and 3-years were 41.5% (95% CI: 28.2 – 54.8%), 15.2% (95% CI: 4.8 – 25.6%) and 6.1% (95%CI: 0 – 15.9%), respectively. Twenty-eight pts received RT/TMZ, and 25 pts RT alone. mOS was 11.6 months (95% CI: 8.6 – 14.6) following RT/TMZ and 9.3 months (95% CI: 8.1 – 10.6) following RT alone. mOS for pts with MGMT methylated status (n = 17) was 13.5 months (95% CI: 7.7 – 19.2), being 17.2 months (95% CI: 11.5 - 22.9) in those treated with RT/TMZ (n = 6) and 8.8 months (95% CI: 2 – 15.6) in those treated with RT alone (n = 11, p = 0.09). Elderly pts with MGMT unmethylated status (n = 25) had a mOS of 8.5 months (95% CI: 6 – 11, p = 0.014), being 8.5 months (95% CI: 2.3 – 14.7) in pts treated with RT/TMZ (n =10), and 8 months (95% CI: 3 – 12.9) in those treated with RT (n = 15, p = 0.55). Conclusions: RT/TMZ appears to be more effective in prolonging the mOS of elderly pts in those with MGMT methylation status (17.2 vs 8.5 months), and seem to perform better than TMZ alone, for which mOS was 9.7 months in the Nordic phase III trial. These findings underline the value of the ongoing randomized EORTC 26062-22061/NCIC CE.6 phase III comparing RT/TMZ with short course RT alone.

Relationship between hospital surgical volume, lobectomy rates, and adverse perioperative events at US epilepsy centers

2013 ◽  
Vol 118 (1) ◽  
pp. 169-174 ◽  
Author(s):  
Dario J. Englot ◽  
David Ouyang ◽  
Doris D. Wang ◽  
John D. Rolston ◽  
Paul A. Garcia ◽  
...  
Keyword(s):  
Relative Risk ◽  
Epilepsy Surgery ◽  
Intractable Epilepsy ◽  
High Volume ◽  
Population Based ◽  
Treatment Center ◽  
Surgical Volume ◽  
Related Factors ◽  
Perioperative Morbidity ◽  
Low Volume

Object Epilepsy surgery remains significantly underutilized. The authors recently reported that the number of lobectomies for localized intractable epilepsy in the US has not changed despite the implementation of clear evidence-based guidelines 10 years ago supporting early referral for surgery. To better understand why epilepsy surgery continues to be underused, the authors' objective was to carefully examine hospital-related factors related to the following: 1) where patients are being admitted for the evaluation of epilepsy, 2) rates of utilization for surgery across hospitals, and 3) perioperative morbidity between hospitals with low versus high volumes of epilepsy surgery. Methods The authors performed a population-based cohort study of US hospitals between 1990 and 2008 using the Nationwide Inpatient Sample (NIS), stratifying epilepsy surgery rates and trends as well as perioperative morbidity rates by hospital surgical volume. Results The number of lobectomies for epilepsy performed at high-volume centers (> 15 lobectomies/year) significantly decreased between 1990 and 2008 (F = 20.4, p < 0.001), while significantly more procedures were performed at middle-volume hospitals (5–15 lobectomies/year) over time (F = 16.1, p < 0.001). No time trend was observed for hospitals performing fewer than 5 procedures per year. However, patients admitted to high-volume centers were significantly more likely to receive lobectomy than those at low-volume hospitals (relative risk 1.05, 95% CI 1.03–1.08, p < 0.001). Also, the incidence of perioperative adverse events was significantly higher at low-volume hospitals (12.9%) than at high-volume centers (6.1%) (relative risk 1.08, 95% CI 1.03–1.07, p < 0.001). Conclusions Hospital volume is an important predictor of epilepsy surgery utilization and perioperative morbidity. Patients with medically refractory epilepsy should be referred to a comprehensive epilepsy treatment center for surgical evaluation by an experienced clinical team.

Real-world experience with docetaxel for castration-sensitive prostate cancer from a population-based analysis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 297-297 ◽  
Author(s):  
Jean-Michel Lavoie ◽  
Kevin Zou ◽  
Daniel Khalaf ◽  
Bernhard J. Eigl ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Performance Status ◽  
Clinical Effectiveness ◽  
High Volume ◽  
Population Based ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Cancer Agency ◽  
Grade 3

297 Background: Phase III clinical trials have demonstrated efficacy with an overall survival (OS) benefit for the addition of docetaxel (DOC) to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). The clinical effectiveness of DOC with ADT in the general patient population remains undefined. Methods: A population-based retrospective review was conducted of patients (pts) with mCSPC who received DOC at the BC Cancer Agency from 04/2015 to 02/2017. Patient and disease characteristics were extracted. Safety and clinical-effectiveness were evaluated. Results: 183 records were identified; 156 pts received DOC in the mCSPC setting. Baseline characteristics included a median age of 67 years (range 44-86) and visceral metastases (mets) present in 18%; 80% had high volume disease with 74% having > 3, and 54% > 10 bone mets; 76% had de-novo metastatic disease. All 6 planned DOC cycles were delivered in 126 cases (81%); it was stopped early for: toxicity in 15 (10%), unrelated death in 1 (0.6%), pt preference in 5 (3%) or disease progression in 9 (6%) cases. Dose reductions and delays were required in 61 (39%) and 25 (16%) cases, respectively. Grade 3-5 adverse events were noted in 62 (40%) cases, with 28 (18%) cases of febrile neutropenia (FN); there were no treatment-related deaths. Pts with FN had more bone mets (p = 0.046), but there was no difference in time from start of ADT to initiation of docetaxel, age, baseline performance status, PSA, or visceral involvement. PSA ≤ 0.2 ng/L was achieved in 41 (28%) cases after 6 months of ADT and maintained in 13 (8%) cases after 12 months. 41% of pts had developed CRPC within 1-yr, with a median time to CRPC of 14.3 months. Treatment for CRPC was given in 54 cases, with most pts receiving either abiraterone or enzalutamide (87%) with a PSA decline ≥50% occurring in 47%. Conclusions: Effectiveness of DOC with ADT in a general population of pts with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the phase III studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to those previously reported.

scholarly journals Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy

2011 ◽  
Vol 55 (12) ◽  
pp. 5421-5429 ◽  
Author(s):  
Howard Takiff ◽  
Elba Guerrero
Keyword(s):  
Multidrug Resistant ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
First Line ◽  
Current Standard ◽  
Standard Drug ◽  
First Line Therapy ◽  
Development Of Resistance ◽  
Mdr Tb ◽  
Phase Iii Trials

ABSTRACTWhile fluoroquinolones (FQs) have been successful in helping cure multidrug-resistant tuberculosis (MDR TB), studies in mice have suggested that if used as first-line agents they might reduce the duration of therapy required to cure drug-sensitive TB. The results of phase II trials with FQs as first-line agents have been mixed, but in at least three studies where moxifloxacin substituted for ethambutol, there was an increase in the early percentage of sputa that converted to negative for bacilli. Phase III trials are in progress to test the effectiveness of 4-month FQ-containing regimens, but there is concern that the widespread use of FQs for other infections could engender a high prevalence of FQ-resistant TB. However, several studies suggest that despite wide FQ use, the prevalence of FQ-resistant TB is low, and the majority of the resistance is low-level. The principal risk for resistance may be when FQs are used to treat nonspecific respiratory symptoms that are in fact TB, so curtailing this use of FQs could reduce the development of resistance and also the delays in TB diagnosis and treatment that have been documented when an FQ is given in this setting. While the future of FQs as first-line therapy will likely depend upon the results of the ongoing phase III trials, if they are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.

Phamacokinetics of rivaroxaban in adolescents

2014 ◽  
Vol 34 (01) ◽  
pp. 85-87 ◽  
Author(s):  
S. Gehrisch ◽  
J. Beyer-Westendorf
Keyword(s):  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Adult Patients ◽  
Phase Iii ◽  
Attractive Alternative ◽  
Current Standard ◽  
Vein Thrombosis ◽  
Phase Iii Trials ◽  
Current Standard Treatment

SummaryBackground: The direct factor Xa inhibitor rivaroxaban is approved for venous throm-boembolism (VTE) treatment in adults. However, in all phase-III trials children or adolescents have not been included. For under-aged VTE patients, current standard treatment consists of low molecular weight heparin or Vitamin K antagonists. Rivaroxaban could be an attractive alternative, however, no data on the pharmacokinetics (PK) of rivaroxaban in adolescents are currently available.Patient, methods: We report PK data for rivaroxaban derived from a girl (age:15 years), who presented three month after acute deep vein thrombosis, already receiving rivaroxaban therapy. In the steady state of rivaroxaban therapy (20 mg once daily), plasma levels at baseline, 3 and 6 hours after intake of rivaroxaban were measured to evaluate the pharmacokinetics and changes of global coagulation tests.Results: At baseline, a very low trough level of only 9.9 ng/ml rivaroxaban was found. At 3 hours, a peak concentration of 137.76 ng/ml rivaroxaban was observed with a rapid decrease within 6 hours after drug intake, when plasma levels of 34.45 ng/ml were measured. The patients INR and aPTT values reacted correspondingly.Conclusion: Our data indicate that adolescents may exhibit lower peak and trough levels after rivaroxaban intake compared to adult patients, but seem to have similar PK curves during the elimination phase. While our case is the first published case of a successful VTE treatment in an under-aged , we strongly discourage the routine use of rivaroxaban in non-adult patients, until data from phase II and III trials are available.

scholarly journals Therapeutic Antibodies for the Treatment of Pancreatic Cancer

2010 ◽  
Vol 10 ◽  
pp. 1107-1120 ◽  
Author(s):  
Patrick Chames ◽  
Brigitte Kerfelec ◽  
Daniel Baty
Keyword(s):  
Pancreatic Cancer ◽  
Target Therapy ◽  
Symptom Control ◽  
Clinical Results ◽  
Phase Iii ◽  
General View ◽  
Cancer Therapies ◽  
Current Standard ◽  
Phase Iii Trials ◽  
Novel Therapeutic Strategies

Pancreatic cancer is a devastating disease with the worst mortality rate and an overall 5-year survival rate lower than 5%. In the U.S., this disease is the fourth leading cause of death and represents 6% of all cancer-related deaths. Gemcitabine, the current standard first-line treatment, offers marginal benefits to patients in terms of symptom control and prolongation of life. Since 1996, about 20 randomized phase III trials have been performed to improve the efficacy of gemcitabine, with little success regarding a significant improvement in survival outcomes. The need for novel therapeutic strategies, such as target therapy, is obvious. Monoclonal antibodies have finally come of age as therapeutics and several molecules are now approved for cancer therapies. This review aims to give a general view on the clinical results obtained so far by antibodies for the treatment of pancreatic cancer and describes the most promising avenues toward a significant improvement in the treatment of this frustrating disease.

Short and long-term survival in metastatic pancreatic adenocarcinoma, 1993-2013.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 232-232 ◽  
Author(s):  
Talia Golan ◽  
Tal Sela ◽  
Ofer Margalit ◽  
Uri Amit ◽  
Naama Halpern ◽  
...  
Keyword(s):  
Marital Status ◽  
Tumor Location ◽  
Population Based ◽  
Phase Iii ◽  
Term Survival ◽  
Modest Improvement ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Study Population ◽  
One Year

232 Background: Over the previous two decades several new agents have been approved for the treatment of metastatic pancreatic cancer (mPDAC). Their efficacy was demonstrated amongst highly selected patients that participate in randomized phase III trials, hence it is not clear to what extent these advances are reflected within the broader mPDAC population. We performed a population-based survival analysis of newly diagnosed patients who presented with mPDAC. Methods: Survival statistics were extracted from the Survival, Epidemiology and End Results (SEER) Database for patients diagnosed with mPDAC between 1993-2013. Demographic variables collected included age, gender, race, and marital status. Tumor characteristics collected included location and grade. Survival was analyzed using the Kaplan-Meier method and proportional hazard models as appropriate. Exclusion criteria included diagnosis at autopsy, unknown histology and pancreatic neuroendocrine tumors. Results: The study population consisted of 57,263 patients diagnosed with mPDAC from 1993-2013, 52% male, median age 69 years (range 15-104). Prognosis correlated with age, gender, race, marital status, tumor location, grade and year of diagnosis. Median overall survival (OS) stayed stable at 2 months between 1993 and 2013. Improvements in OS were seen for all patients, but especially for younger patients ( < 50 years of age) and more recent year of diagnosis group (2009-2013). The percentage of patients who died within two months of initial diagnosis decreased between 1993 and 2013 (from 63.5% to 50.6%, p < 0.0001). The subgroup of patients achieving longer-term survival has increased, with 12-month survival improving from 4.9 % to 12.7% (p < 0.0001) between 1993 and 2013. Conclusions: There has been a continuous but modest improvement in OS of patients diagnosed with mPDAC between 1993 and 2013. The percentage of patients living beyond one year has significantly increased over time; however the percentage of patients dying within 2 months has only slightly decreased.

Frequency and Timing of Endovascular Therapy in Acute Stroke Patients: A Population-Based Analysis Using the Bremen Stroke Register

2020 ◽  
Vol 54 (5) ◽  
pp. 398-403
Author(s):  
Andreas Kastrup ◽  
Freimuth Brunner ◽  
Christian Roth ◽  
Panagiotis Papanagiotou
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Standard Of Care ◽  
High Volume ◽  
Absolute Number ◽  
Population Based ◽  
Stroke Patients ◽  
Anterior Circulation ◽  
High Volume Center ◽  
Stroke Register

<b><i>Background and Purpose:</i></b> In patients with large vessel occlusions (LVOs), endovascular treatment (ET) has become the standard of care, so that the potential number of these patients needs to be considered for the effective implementation of comprehensive stroke services. However, population-based data on the incidence of ET are scarce. <b><i>Methods:</i></b> Using our prospective stroke register, in which all endovascular procedures on the 557,464 inhabitants of the city of Bremen are included, we performed a population-based analysis on the frequency and timing of ET in acute stroke patients with LVOs in the year 2017. <b><i>Results:</i></b> Out of a total of 1,448 acute ischemic stroke patients, 173 patients (12%) had received ET (161 patients in the anterior circulation and 12 patients in the posterior circulation). Among these, 95 patients were inhabitants of Bremen. The population-based incidence thus was 17 (95% confidence interval [CI]: 14–21) ET cases per 100,000 person-years. The number of stroke procedures per month varied from 9 to 19 (median: 14.5; interquartile range [IQR]: 12–17). The number of stroke procedures per month and 100,000 inhabitants varied from 0.7 to 2.1 (median: 1.4; IQR: 0.9–1.7). Many procedures (53%) were performed during nonwork hours (between 17:00 h and 06:59 h or weekends). <b><i>Conclusions:</i></b> Approximately 12% of all ischemic stroke patients received ET, and the incidence of ET was 17 (95% CI: 14–21) cases per 100,000 person-years. However, despite being a high-volume center, the absolute number of stroke procedures per month was low, and many patients were treated during nonwork hours.

scholarly journals Testing many treatments within a single protocol over 10 years at MRC Clinical Trials Unit at UCL: Multi-arm, multi-stage platform, umbrella and basket protocols

2017 ◽  
Vol 14 (5) ◽  
pp. 451-461 ◽  
Author(s):  
Mahesh KB Parmar ◽  
Matthew R Sydes ◽  
Fay H Cafferty ◽  
Babak Choodari-Oskooei ◽  
Ruth E Langley ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Iii ◽  
Current Standard ◽  
New Methods ◽  
Multi Stage ◽  
Phase Iii Trials ◽  
Clinical Trials Unit ◽  
New Treatment ◽  
Better Than ◽  
Phase I And Ii

There is real need to change how we do some of our clinical trials, as currently the testing and development process is too slow, too costly and too failure-prone often we find that a new treatment is no better than the current standard. Much of the focus on the development and testing pathway has been in improving the design of phase I and II trials. In this article, we present examples of new methods for improving the design of phase III trials (and the necessary lead up to them) as they are the most time-consuming and expensive part of the pathway. Key to all these methods is the aim to test many treatments and/or pose many therapeutic questions within one protocol.

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