Apalutamide (APA) for metastatic castration-sensitive prostate cancer (mCSPC) in TITAN: Outcomes in patients (pts) with low- and high-risk disease.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 87-87 ◽  
Author(s):  
Mustafa Ozguroglu ◽  
Simon Chowdhury ◽  
Anders Bjartell ◽  
Hirotsugu Uemura ◽  
Byung Ha Chung ◽  
...  

87 Background: TITAN showed that APA + androgen deprivation therapy (ADT) improves radiographic progression-free survival (rPFS) and overall survival (OS) in a broad group of pts with mCSPC (Chi et al. NEJM 2019). This post hoc analysis evaluates APA + ADT based on baseline (BL) prognostic risk as defined in LATITUDE (Fizazi et al. Lancet Oncol 2019). Methods: 1052 pts with mCSPC receiving ADT were randomized 1:1 to APA (240 mg/d; n = 525) or placebo (PBO; n = 527). Treatment cycles were 28 days. Risk included Gleason score ≥ 8, ≥ 3 bone lesions, or visceral metastasis. High risk was ≥ 2 risk factors, low risk was ≤ 1. Cox proportional hazards model was used to estimate HR and 95% CI for rPFS and OS. Results: Pt demographic and BL disease characteristics were similar between treatment groups (high risk: APA n = 289, PBO n = 286; low risk: APA n = 236, PBO n = 241). Median treatment duration was similar in the low-risk group with APA or PBO (21.8 mo and 20.3 mo, respectively). For the high-risk groups, treatment duration was longer with APA (APA 19.5 mo, PBO 14.7 mo). APA significantly reduced the risk of radiographic progression relative to PBO in both groups (Table). Risk of death (OS) was reduced by 38% in high-risk pts and 26% in low-risk pts with APA (Table). 24-mo survival rates: high risk, 76% APA, 63% PBO; low risk, 90% APA, 85% PBO. There were few deaths (≤ 33) in low-risk groups. Second PFS in APA pts: high risk, HR 1.9 (95% CI 1.2-3.0), p = 0.004; low risk, HR 2.2 (95% CI 1.5-3.2), p < 0.0001. Regardless of risk category, the safety profile of APA remained consistent with previously reported overall results. Conclusions: Addition of APA to ADT for pts with mCSPC prolonged rPFS and OS with a consistent safety profile compared with PBO + ADT regardless of BL risk. Clinical trial information: NCT02489318. [Table: see text]

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 813-813
Author(s):  
R.H. Advani ◽  
H. Chen ◽  
T.M. Habermann ◽  
V.A. Morrison ◽  
E. Weller ◽  
...  

Abstract Background: We reported that addition of rituximab (R) to chemotherapy significantly improves outcome in DLBCL patients (pt) &gt;60 years (JCO24:3121–27, 2006). Although the IPI is a robust clinical prognostic tool in DLBCL, Sehn et al (ASH 2005: abstract 492) reported that a revised (R) IPI more accurately predicted outcome in pt treated with rituximab-chemotherapy. Methods: We evaluated outcomes of the Intergroup study with respect to the standard IPI, R-IPI, age-adjusted (aa) IPI for evaluable pt treated with R-CHOP alone or with maintenance rituximab. We further assessed a modified IPI (mIPI) using age ≥ 70 y as a cutoff rather than age 60 y. Results: The 267 pt in this analysis were followed for a median of 4 y. Pt characteristics were: age &gt; 70 (48%) (median=69), male 52%, stage III/IV 75%, &gt;1 EN site 30%, LDH elevated 60%, PS ≥2 15%. On univariate analysis all of these characteristics were significant for 3 y failure-free survival (FFS) and overall survival (OS). The IPI provided additional discrimination of risk compared to the R-IPI with significant differences in FFS and OS for 3 vs 4–5 factors. The aa-IPI defined relatively few pt as low or high risk. The impact of age was studied using a cut-off of 70 years in a modified IPI, yielding 4 risk groups as shown below. Conclusions: For pt ≥ 60 treated with rituximab-chemotherapy the distinction between 3 vs 4,5 factors in the IPI was significant.The IPI also provided additional discrimination of risk compared to the R-IPI. In this older group of pt, use of an age cutoff ≥70 y placed more patients in the low risk category. It is of interest to apply the mIPI in other datasets with DLBCL pt &gt;60 y. Group # Factors # Pt % 3y FFS* % 3y OS* *All risk groups significantly different; logrank p &lt; 0.001 **95 % CI: FFS (0.46,0.66), OS (0.58,0.78) ***95 % CI: FFS (0.21,0.45), OS (0.31,0.55) L: Low, LI: Low Intermediate, HI: High Intermediate, H; High IPI L 0–1 12 78 83 LI 2 28 70 80 HI 3 33 56** 68** H 4–5 37 33*** 43*** R-IPI Very Good 0 0 - - Good 1–2 40 72 81 Poor 3–5 60 46 57 aa-IPI L 0 12 78 83 LI 1 35 68 78 HI 2 44 47 59 H 3 9 31 35 mIPI (age ≥ 70) L 0–1 27 77 86 LI 2 28 62 74 HI 3 29 47 58 H 4–5 16 28 36


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Naveen Prashar ◽  
Rahuldeep Singh ◽  
Ritin Mohindra ◽  
Vikas Suri ◽  
Ashish Bhalla ◽  
...  

Abstract Background WHO has declared the COVID-19 as Pandemic on 11th March, 2020. It is important to break the chain of transmission by quarantining the persons with high-risk exposure. Understanding the reasons for quarantine will help in reducing the exposures and thus reducing the chances of quarantine. Methods A validated risk assessment tool based on National Centre for Disease Control guidelines was used for the risk assessment of HCWs. The forms of HCWs who underwent risk assessment between April-November, 2020 were analyzed for reasons of quarantine. The positivity rates among high-risk and low-risk groups were compared. Results Out of 1414 HCWs who were assessed, 345 were categorized as high-risk exposure and were quarantined. The most common reasons for quarantine were performance of aerosol generating procedure without recommended personal protection equipment (PPE) (34%), exposure to COVID-19 positive patient without mask for more than 20 minutes at the distance less than 1 m (30%) and having food/tea together (27%). The positivity rate was 8.4% among high-risk and 1.9% among low-risk exposure group (p-value: &lt;0.001). The positivity among low risk category was more in the second half (19/466; 4.1%) as compared to first half (1/603; 0.2%) of the study period. This might be due to exposure from non-hospital sources as second half coincides with first wave of the pandemic. Conclusion Not using recommended PPE and having tea/food breaks together were the most common reasons for quarantine. Key messages Strict enforcement of recommended PPE and scattered tea and food breaks can reduce high-risk exposures.


Author(s):  
Lars Sävendahl ◽  
Michel Polak ◽  
Philippe Backeljauw ◽  
Joanne C Blair ◽  
Bradley S Miller ◽  
...  

Abstract Context GH treatment has a generally good safety profile; however, concerns of increased mortality risk in adulthood have been raised. Objective Assessing the long-term safety of GH treatment in clinical practice. Design Two multicenter longitudinal observational studies: NordiNet® International Outcome Study (2006–2016, Europe) and ANSWER Program (2002–2016, USA). Setting Data collected from 676 clinics. Patients Pediatric patients treated with GH, classified into three risk groups based on diagnosis. Intervention Daily GH treatment. Main Outcome Measures Incidence rates (events/1000 patient-years) of adverse drug reactions (ADRs), serious adverse events (SAEs), and serious ADRs, and their relationship to the GH dose. Results The combined studies comprised 37,702 patients (68.4% in low-risk, 27.5% in intermediate-risk, and 4.1% in high-risk groups) and 130,476 patient-years of exposure. The low-risk group included children born small for gestational age (SGA; 20.7%) and non-SGA children (e.g. with GH deficiency; 79.3%). Average GH dose up to the first adverse event (AE) decreased with increasing risk category. Patients without AEs received higher average GH doses than patients with &gt;1 AE across all groups. A significant inverse relationship with GH dose was shown for ADR and SAE incidence rates in the low-risk group (P = 0.0029 and P = 0.0003, respectively) and the non-SGA subgroup (P = 0.0022 and P = 0.0015, respectively), and for SAEs in the intermediate- and high-risk groups (P = 0.0017 and P = 0.0480, respectively). Conclusions We observed no indication of increased mortality risk nor AE incidence related to GH dose in any risk group.


2004 ◽  
Vol 22 (16) ◽  
pp. 3316-3322 ◽  
Author(s):  
Jean-Jacques Patard ◽  
Hyung L. Kim ◽  
John S. Lam ◽  
Frederick J. Dorey ◽  
Allan J. Pantuck ◽  
...  

Purpose To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. Patients and Methods 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. Results The UISS stratified both localized and metastatic RCC into three different risk groups (P < .001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. Conclusion This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11016-11016 ◽  
Author(s):  
Sandro Pasquali ◽  
Chiara Colombo ◽  
Stefano Bottelli ◽  
Paolo Verderio ◽  
Javier Martin Broto ◽  
...  

11016 Background: Patients with extremity and trunk wall STS with high malignancy grade and size larger than 5cm are considered at high risk of death, but in fact this risk varies broadly depending on histologic subtype and size. The Sarculator, a nomogram for STS, can improve prognostic assessment of these patients. This tool was evaluated for stratifying risk of distant metastasis (DM) and overall survival (OS) in a RCT investigating perioperative chemotherapy. Methods: High-risk STS patients were randomly assigned to receive either three cycles of preoperative chemotherapy with epirubicin (120 mg/m2) and ifosfamide (9 g/m2) or the same three preoperative cycles followed by two further postoperative cycles. The Sarculator was used to stratify patient risk according to predicted 10-year cumulative incidence of DM and OS rates. Results: The Sarculator identified three different prognostic groups of patients at low (N = 101), intermediate (N = 102), and high (N = 107) risk. Cumulative incidence of DM was 0.26 (SE: 0.04), 0.31 (SE: 0.05), and 0.48 (SE: 0.05) for low, intermediate, and high risk patients, respectively. Similarly, OS rates were 0.78 (95%CI 0.68-0.85), 0.63 (95%CI 0.53-0.72), and 0.42 (95%CI 0.32-0.52), respectively. Patients in the low risk group were at significantly lower risk of death compared to those in the intermediate (HR 0.51, 95%CI 0.34-0.78, P = 0.002) and high (HR 0.28, 95%CI 0.17-0.46, P < 0.001) risk groups. Subgroup analysis performed by jointly considering these three groups and the two study arms did not identify statistically significant survival differences between the treatment arms within each risk category. Conclusions: Patients with high-risk STS included in this RCT were not a homogeneous population. The Sarculator identified different risk groups for DM and OS even in patients included in a RCT investigating perioperative treatments. This tool should be considered for redefining high-risk STS and stratifying patient risk in future RCT investigating perioperative chemotherapy. Clinical trial information: 2004-003979-36.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 753-753
Author(s):  
Margaret Frances Meagher ◽  
Ricardo Autorino ◽  
Maximilian Kriegmair ◽  
Maria Carmen Mir ◽  
Jose Rubio ◽  
...  

753 Background: The role of metastasectomy has been in flux as treatment paradigms for management of metastatic renal cell carcinoma (mRCC) have shifted. We examined outcomes of surgical metastasectomy stratified in the setting of different mRCC risk groups. Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was subdivided by Motzer RCC criteria (low, intermediate, and high risk), and impact of metastasectomy was analyzed via multivariable analysis (MVA) and Kaplan Meier analyses (KMA). Primary outcome was progression free survival (PFS) and secondary outcome was overall survival (OS). Results: 438 patients (46 low risk, 262 intermediate risk, 140 high risk) with median follow-up 16 months were analyzed. Metastasectomy was performed in 18 (39%), 63 (24%), and 32 (23%) of low, intermediate and high risk groups (p=0.04). Risk groups differed significantly with respect to ECOG performance status (p<0.001), metastases at diagnosis (low 1.72, intermediate 3.49, high 6.45, p<0.001), hemoglobin (p<0.001) and LDH (p<0.001). MVA for PFS revealed age (OR=1.03, p=0.05), BMI (OR=1.05, p=0.01), and higher risk category [vs. low (referent) intermediate OR=7.4, p<0.001, high OR=3.4, p=0.01] to be independent risk factors. MVA for OS revealed age (OR=1.03, p=0.02), BMI (OR=1.06, p=0.01), and higher risk category [low (referent) vs. intermediate OR=2.8, p=0.03, high OR=2.3, p=0.01] to be independent risk factors. KMA for PFS demonstrated that metastasectomy was associated with longer PFS in intermediate (24.0 vs. 6.7 months, p=0.01) but not high risk (4.2 vs. 4.0 months, p=0.58) and low risk (p=0.51) groups. KMA for OS demonstrated that metastasectomy was associated with longer median OS in the intermediate (56.9 vs. 29.3 months, p=0.01) and high risk (18.2 vs. 10.5, p=0.01), but not low risk (p=0.21) groups. Conclusions: Receipt of metastasectomy was associated with improved PFS in intermediate risk and improved OS in intermediate and high risk mRCC patients. These findings challenge prevailing assumptions about utility of metastasectomy. Further investigation is requisite to refine criteria for employment.


2014 ◽  
Vol 111 (01) ◽  
pp. 53-57 ◽  
Author(s):  
Cecilia Becattini ◽  
Emanuele Guglielmelli ◽  
Irene Floriani ◽  
Vincenzo Morrone ◽  
Carla Caponi ◽  
...  

SummaryThe exact prevalence of mobile right heart thromboemboli (RHTh) in patients with pulmonary embolism (PE) is unknown, depending upon PE severity and the use of early echocardiography. Similarly, the mortality rate is variable, though RHTh detection appears to substantially increase the risk of death in patients with PE. The aim of this study was to assess the prevalence of RHTh in different risk categories in a wide series of patients with PE, and to analyse the effect of RHTh on in-hospital mortality. Among 1,716 patients enrolled in the Italian Pulmonary Embolism Registry, 1,275 (13.3% at high risk, 59.3% at intermediate risk and 27.4% at low risk) had echocardiography within 48 hours from hospital admission and entered the study. Overall, RHTh were detected in 57 patients (4.5%, at admission echocardiography in 88%): in 27/169 (16%) high-risk, in 29/756 (3.8%) intermediate-risk and 1/350 (0.3%) low-risk patients, respectively. At multivariate analysis, only advanced age (odds ratio [OR] 1.61, 95% confidence [CI] 1.27–2.03, p<0.0001), high-risk category (OR vs low-risk category 37.82, 95% CI 11.26–127.06, p<0.0001) and recurrent PE (OR 45.92, 95%CI 15.19–139.96, p<0.0001) showed a statistically significant effect on mortality. The presence of RHTh significantly increased the risk of dying (OR 3.89, 95%CI 1.98–7.67, p=0.0001) at univariate analysis, but this result was not mantained in the multivariate model (OR 1.64, 95%CI 0.75–3.60, p=0.216). In conclusion, though patients with RHTh had a more severe presentation of PE, this study did not detect an association between RHTh and prognosis.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heba Alshaker ◽  
Robert Mills ◽  
Ewan Hunter ◽  
Matthew Salter ◽  
Aroul Ramadass ◽  
...  

Abstract Background Current diagnostic blood tests for prostate cancer (PCa) are unreliable for the early stage disease, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance of negative biopsies in men with PCa. Predicting the risk of PCa is pivotal for making an informed decision on treatment options as the 5-year survival rate in the low-risk group is more than 95% and most men would benefit from surveillance rather than active treatment. Three-dimensional genome architecture and chromosome structures undergo early changes during tumourigenesis both in tumour and in circulating cells and can serve as a disease biomarker. Methods In this prospective study we screened whole blood of newly diagnosed, treatment naïve PCa patients (n = 140) and cancer-free controls (n = 96) for the presence of 14,241 chromosomal loops in the loci of 425 genes. Results We have detected specific chromosome conformation changes in the loci of ETS1, MAP3K14, SLC22A3 and CASP2 genes in peripheral blood from PCa patients yielding PCa detection with 80% sensitivity and 80% specificity. Further analysis between PCa risk groups yielded prognostic validation sets consisting of HSD3B2, VEGFC, APAF1, BMP6, ERG, MSR1, MUC1, ACAT1 and DAPK1 genes that achieved 80% sensitivity and 93% specificity stratifying high-risk category 3 vs low risk category 1 and 84% sensitivity and 89% specificity stratifying high risk category 3 vs intermediate risk category 2 disease. Conclusions Our results demonstrate specific chromosome conformations in the blood of PCa patients that allow PCa diagnosis and risk stratification with high sensitivity and specificity.


2021 ◽  
Vol 6 (1) ◽  
pp. e004614
Author(s):  
John P A Ioannidis

The ability to preferentially protect high-risk groups in COVID-19 is hotly debated. Here, the aim is to present simple metrics of such precision shielding of people at high risk of death after infection by SARS-CoV-2; demonstrate how they can estimated; and examine whether precision shielding was successfully achieved in the first COVID-19 wave. The shielding ratio, S, is defined as the ratio of prevalence of infection among people in a high-risk group versus among people in a low-risk group. The contrasted risk groups examined here are according to age (≥70 vs <70 years), and institutionalised (nursing home) setting. For age-related precision shielding, data were used from large seroprevalence studies with separate prevalence data for elderly versus non-elderly and with at least 1000 assessed people≥70 years old. For setting-related precision shielding, data were analysed from 10 countries where information was available on numbers of nursing home residents, proportion of nursing home residents among COVID-19 deaths and overall population infection fatality rate (IFR). Across 17 seroprevalence studies, the shielding ratio S for elderly versus non-elderly varied between 0.4 (substantial shielding) and 1.6 (substantial inverse protection, that is, low-risk people being protected more than high-risk people). Five studies in the USA all yielded S=0.4–0.8, consistent with some shielding being achieved, while two studies in China yielded S=1.5–1.6, consistent with inverse protection. Assuming 25% IFR among nursing home residents, S values for nursing home residents ranged from 0.07 to 3.1. The best shielding was seen in South Korea (S=0.07) and modest shielding was achieved in Israel, Slovenia, Germany and Denmark. No shielding was achieved in Hungary and Sweden. In Belgium (S=1.9), the UK (S=2.2) and Spain (S=3.1), nursing home residents were far more frequently infected than the rest of the population. In conclusion, the experience from the first wave of COVID-19 suggests that different locations and settings varied markedly in the extent to which they protected high-risk groups. Both effective precision shielding and detrimental inverse protection can happen in real-life circumstances. COVID-19 interventions should seek to achieve maximal precision shielding.


2020 ◽  
Author(s):  
John P.A. Ioannidis

ABSTRACTBackgroundThe ability to preferentially protect high-groups in COVID-19 is hotly debated. Here, the aim is to present simple metrics of such precision shielding of people at high-risk of death after infection by SARS-CoV-2; demonstrate how they can estimated; and examine whether precision shielding was successfully achieved in the first COVID-19 wave.MethodsThe shielding ratio, S, is defined as the ratio of prevalence of infection among people at a high-risk group versus among people in a low-risk group. The contrasted risk groups examined here are according to age (>=70 versus <70 years), and institutionalized (nursing home) setting. For age-related precision shielding, data were used from large seroprevalence studies with separate prevalence data for elderly versus non-elderly and with at least 1000 assessed people >=70 years old. For setting-related precision shielding, data were analyzed from 10 countries where information was available on numbers of nursing home residents, proportion of nursing home residents among COVID-19 deaths, and overall population infection fatality rate.FindingsAcross 17 seroprevalence studies, the shielding ratio S for elderly versus non-elderly varied between 0.4 (substantial shielding) and 1.6 (substantial inverse protection, i.e. low-risk people being protected more than high-risk people). Five studies in USA all yielded S=0.4-0.8, consistent with some shielding being achieved, while two studies in China yielded S=1.5-1.6, consistent with inverse protection. Assuming 25% infection fatality rate among nursing home residents, S values for nursing home residents ranged from 0.07 to 3.1. The best shielding was seen in South Korea (S=0.07) and modest shielding was achieved in Israel, Slovenia, Germany, and Denmark. No shielding was achieved in Hungary and Sweden. In Belgium (S=1.9), UK (S=2.2) and Spain (S=3.1), nursing home residents were far more frequently infected that the rest of the population.InterpretationThe experience from the first wave of COVID-19 suggests that different locations and settings varied markedly in the extent to which they protected high-risk groups. Both effective precision shielding and detrimental inverse protection can happen in real-life circumstances. COVID-19 interventions should seek to achieve maximal precision shielding.


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