Docetaxel (DOC) versus new androgen receptor-targeted agent (ART) in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) having received abiraterone (ABI) or enzalutamide (ENZA) as first-line (L1).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 109-109
Author(s):  
Antonin Broyelle ◽  
André-Michel Bimbai ◽  
Aurelien Carnot ◽  
Diane Pannier ◽  
Samira Makhloufi ◽  
...  

109 Background: The main treatments for mCRPC are 2 new ART (ABI, ENZA) and 2 taxanes [doctaxel (DOC) and Cabazitaxel]. The optimal sequence is currently not defined. An increasing number of pts are first treated with one of ART. In this population, data about efficacy of 2nd line (L2) are spare. We designed a retrospective study to evaluate activity of DOC vs ART in mCRPC pts treated with ART as L1 therapy. Methods: In this observational cohort study, we included all consecutive pts with ENZA or ABI as L1 for chemo-naïve mCRPC. We measured PFS and OS during both L1 & L2. To compare the efficacy of DOC versus ART as L2, we measured Growth Modulation Index (GMI=Time To progression with L2/TTP with L1) and we used Cox model to compare PFS/OS in both arm, in both univariate & multivariate analysis using propensity score. Results: We included 175 pts, including 75 treated ENZA and 100 with ABI as L1. 69 (39%) pts received DOC and 30 (17%) pts received ART as L2; 76 (43%) did not receive L2. Median follow-up was 36 months (CI95%: 30.4 - 40). From the starting of L1, PFS was 13.0 months (CI95% 11.0 – 15.0), OS was 34.5 months (CI95%: 28.7 – 38.6). There was no difference between ENZA and ABI in PFS and OS (p=0.684). From the start of L2, the median PFS was 6.0 months (CI95%: 5.0 – 6.6) and the median OS was 18.0 months (CI95%: 13.9 – 21.4). We found a significant benefit in PFS for DOC vs ART in L2 (6.7 months vs 4.0 months, HR 0.60 [CI95%: 0.31 – 0.96], p=0.03). This benefit did not reach the level of significance in OS (19.5 months vs 12.0 months, HR 0.60 [CI95%: 0.35 – 1.03], p=0.1). ECOG-PS and time of castration resistance were associated with OS in multivariable analysis and then used in propensity score. After adjustment to both parameters, we found no difference in PFS (p=0.2) and OS (p=0.1) in pts receiving DOC vs ART as L2. Only 56% of pts received L2. Probability for GMI being >1.33 was not significantly different between DOC (19%) and ART (13%), p=0.099. Conclusions: ABI and ENZA are similarly active in L1 mCRPC. In univariate analysis, L2 with DOC seemed more active than ART. However this benefit was not retained after adjustment to propensity score.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10011-10011 ◽  
Author(s):  
S. Richman ◽  
M. S. Braun ◽  
J. W. Adlard ◽  
C. Daly ◽  
F. Turner ◽  
...  

10011 Background: We previously presented (ASCO 04 #9506) an exploratory analysis of 13 molecular markers in relation to clinical outcomes in 846 patients treated with fluorouracil (FU), or FU+irinotecan, or FU+oxaliplatin in a large UK-based randomized controlled trial (FOCUS - ASCO ’05 #3518). High TS IHC expression and tumor grade were highly significantly associated with reduced failure-free survival (FFS) in a multivariable model. We now present data from an independent validation set of 449 FOCUS patients and on the combined test and validation sets. Methods: Formalin-fixed, paraffin embedded blocks were retrieved from consenting patients and tissue microarrays made for IHC assessment. Factors assessed for the effect on FFS of first-line therapy were: liver metastases; ALP; grade; mucoid status; age; and IHC for dUTPase and TS. Log-rank univariate analyses and Cox Model multivariable analysis was performed. Results: Univariate analysis of the validation set failed to confirm evidence of the previously observed association between high TS expression and FFS (p=0.2); however high dUTPase IHC (p=0.01), ALP (p<0.0001) and grade (p=0.001) showed significant associations. Table 1 illustrates the results of univariate and multivariable analysis of the combined test and validation sets. In the Cox Model, high TS IHC expression, tumor grade and baseline serum ALP were highly significant predictors of reduced FFS. Conclusions: We failed to confirm a significant association between high TS expression and reduced FFS in an independent validation set. However, in an exploratory analysis of the combined validation and test sets (n>1000), TS IHC expression remained a highly significant predictor of FFS. Overall, our results cannot be taken to demonstrate a powerful and clinically useful influence of TS on treatment efficacy, but are consistent with a moderate effect. [Table: see text] No significant financial relationships to disclose.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 136-136
Author(s):  
Michael Thomas Schweizer ◽  
Xian Chong Zhou ◽  
Hao Wang ◽  
Sunakshi Bassi ◽  
Michael Anthony Carducci ◽  
...  

136 Background: Taxanes are hypothesized to mediate their effect in CRPC, at least in part, by disrupting androgen receptor trafficking along microtubules. This raises the possibility of cross-resistance between androgen-directed agents (e.g., Abi) and Tax. Methods: We retrospectively evaluated Tax efficacy in CRPC patients (N=119) who did (Abi+Tax; n=24) or did not (Tax; n=95) receive prior Abi. To ensure a contemporaneous control group, this analysis only included men who started Tax between 12/2007 (the date we began using Abi at our center) and 5/2013. Univariate and propensity score-weighted multivariable analyses for PSA progression-free survival (PSA-PFS) and all-cause progression-free survival (PFS) were conducted to evaluate the effect of prior Abi on responses to Tax. Results: Men in the Abi+Tax group had a significantly higher risk of progression than those in the Tax group. In univariate analysis, PSA-PFS was shorter in the Abi+Tax group (HR 2.00; 95%CI 1.13–3.52; P=0.016), as was PFS (HR 1.97; 95%CI 1.13–3.41; P=0.016). Median PSA-PFS was 4.1 mo in the Abi+Tax group and 6.3 mo in the Tax group (P=0.014). Median PFS was also shorter in the Abi+Tax group (4.1 vs 6.8 mo; P=0.014). In multivariable analysis, prior Abi treatment remained a predictor of shorter PSA-PFS and PFS (Table). PSA declines ≥50% were also less frequent in the Abi+Tax group (37% vs 63%, P=0.04). Conclusions: Men receiving Abi prior to Tax were more likely to develop progression on Tax (and less likely to have a PSA response) than Abi-naive patients. Cross-resistance between Abi and Tax may limit taxane efficacy in Abi-pretreated patients. [Table: see text]


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuanwang Yan ◽  
Hui Yang ◽  
Lili Chen ◽  
Ran Liu ◽  
Wei Shang ◽  
...  

Abstract Background This study aims to investigate the clinical significance and prognostic value of mucinous component (MC) in colorectal adenocarcinoma (AC). Methods Patients with colorectal AC and AC with MC (ACMC) (1–100%) underwent surgical resection between January 2007 and February 2018 were retrospectively reviewed. Propensity score matching (PSM) was performed according to a 1:1 ratio. Receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off value of MC ratio for prognostic prediction. The clinicopathological features and 3-year overall survival (OS) of AC patients, mucinous adenocarcinoma (MAC) (MC > 50%) patients, and ACMC (1–50%) patients were compared before and after matching. Multivariable analysis was used for analyzing independent risk factors related to prognosis. Results A total of 532 patients were enrolled in this study. Patients with AC, MAC, and ACMC (1–50%) exhibited different clinicopathological features. However, their 3-year OS rates were similar (82.00% vs. 74.11% vs. 81.48%, P = 0.38). After matching, ROC curve determined 70% as the optimal cut-off value. And patients with ACMC > 70% had a much poorer 3-year OS compared with ACMC (1–70%) patients and AC patients (47.37% vs. 86.15% vs. 79.76%, P < 0.001). In addition, ACMC > 70% was revealed as a risk factor for poor survival in univariate analysis (HR = 1.643, 95%CI = 1.025–2.635, P = 0.039), though not an independent risk factor in multivariable analysis (HR = 1.550, 95%CI = 0.958–2.507, P = 0.074). Conclusions MAC is usually diagnosed at an advanced stage. MAC has a similar survival with AC and ACMC (1–50%) patients before and after matching. Patients with ACMC > 70% exhibited a much poorer OS, and should be given more clinical attention.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3624-3624
Author(s):  
Leo Chen ◽  
Gillian Gresham ◽  
Winson Y. Cheung ◽  
Hagen F. Kennecke ◽  
Daniel John Renouf

3624 Background: The prognosis of individual pts with mCRC can be highly variable. Our objective was to develop a scoring system to improve the prognostication of mCRC pts at baseline assessment. We also further explored the impact of palliative resection (PR) of the primary tumor on OS. Methods: Pts diagnosed with mCRC from 2006 to 2008, referred to 1 of 5 regional cancer centers in British Columbia were retrospectively reviewed. Pts with prior early stage CRC who relapsed with mCRC were excluded. Multivariate stepwise selection was performed using significant variables from univariate analysis. Patients were assigned a composite risk score (range 0-15) based on their baseline variables, and then separated into quartiles for OS using cut-point analysis and Kaplan Meier methods. A secondary propensity score matched analysis was performed to obtain hazard ratios (HR) for death in order to control for baseline differences between pts who underwent PR and those who did not. Results: A total of 505 mCRC pts were included: median age 63 (range 22-86), 58% male, 75% ECOG 0-1, 58% colon primary, 34% >1 metastatic site, and 46% smokers. In this cohort, 81% of the population underwent PR. ECOG 2-3, no primary resection, colon primary, >1 metastatic site, CEA level >4 ng/ml, male gender, and smoker were significant in the multivariate model and subsequently assigned a score. Median OS varied significantly depending on the composite risk score (table). After ECOG PS, PR of the primary was the second strongest prognostic factor (HR 2.3, 95%CI 1.6-3.3). To further explore this, a propensity score matched analysis was performed adjusting for age, gender, ECOG and receipt of chemotherapy. Prognosis continued to be more favorable in the PR group with a median OS of 17 vs. 7.9 months (HR 0.66, 95% CI 0.50-0.86, p=0.0019). Conclusions: In this population based analysis, the BCCA mCRC score was a simple and effective method to improve prognostication for mCRC pts. PR of the primary was associated with significantly longer OS. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
Saad A. Khan ◽  
Maneka Puligandla ◽  
Suzanne Eleanor Dahlberg ◽  
Gregory A. Masters ◽  
Corey J. Langer ◽  
...  

9051 Background: Up to 50% of advanced NSCLC patients receive radiation therapy at some point in their course. We sought to determine whether patients with prior radiation demonstrate altered outcomes on subsequent metastatic clinical trials. Methods: We reviewed 8 ECOG-ACRIN advanced non-small cell lung cancer studies conducted between 1993 and 2011 in which information was collected about receipt of prior radiation. Whether radiotherapy was given with curative or palliative intent, or to specific sites was not recorded. Median follow-up among all trials was 66 months. We used the log-rank, Wilcoxon and Fisher’s exact tests to compare patients, and Cox Model and Kaplan-Meier method to calculate survival. Results: 574/3041 (18.9%) patients had received prior radiation. These patients were more likely to be male (64% vs 58%), have squamous histology (20% vs 14%) and have had prior surgery (48% vs 33%) compared to those with no prior radiation. At registration, prior radiation patients were more likely to have an ECOG PS of 1 (66% vs 58%), while they were less likely to have a PS of 0 (24% vs 36%) or have a pleural effusion (23% vs 37%). Patients who received radiation were more likely to have been registered on to studies between 1993-1999 than 2000-2011 (69% vs 31%) (all p < 0.001). Median Overall Survival (OS) for patients with prior radiation was 7.6 months (range 7-8.3) vs 9.5 (9.1-9.8) for those without (p < 0.001). Median Progression Free Survival (PFS) for those with prior radiation was 3.5 months (3-3.9) vs 4.2 (4.1-4.4) for those without (p < 0.001). In multivariable analysis controlling for stage IIIB/IV, sex, PS, histology, and prior surgery, the impact of prior radiation on overall survival remained significant (p = 0.042, HR (95% CI) = 1.11 (1.00, 1.22)). Conclusions: Almost one-fifth of lung cancer patients on systemic therapy trials for advanced disease previously received radiation. They are more likely to be male, have squamous histology, have an ECOG PS of 1 and have had prior surgery. Prior radiation is significantly associated with inferior OS and PFS. For advanced NSCLC clinical trials, documentation of whether curative intent/palliative intent radiation was given and stratification by prior radiation exposure should be considered.


2020 ◽  
Vol 133 (6) ◽  
pp. 1863-1872 ◽  
Author(s):  
Hideaki Tanaka ◽  
Jean Gotman ◽  
Hui Ming Khoo ◽  
André Olivier ◽  
Jeffery Hall ◽  
...  

OBJECTIVEThe authors sought to determine which neurophysiological seizure-onset features seen during scalp electroencephalography (EEG) and intracerebral EEG (iEEG) monitoring are predictors of postoperative outcome in a large series of patients with drug-resistant focal epilepsy who underwent resective surgery.METHODSThe authors retrospectively analyzed the records of 75 consecutive patients with focal epilepsy, who first underwent scalp EEG and then iEEG (stereo-EEG) for presurgical assessment and who went on to undergo resective surgery between 2004 and 2015. To determine the independent prognostic factors from the neurophysiological scalp EEG and iEEG seizure-onset information, univariate and standard multivariable logistic regression analyses were used. Since scalp EEG and iEEG data were recorded at different times, the authors matched scalp seizures with intracerebral seizures for each patient using strict criteria.RESULTSA total of 3057 seizures were assessed. Forty-eight percent (36/75) of patients had a favorable outcome (Engel class I–II) after a minimum follow-up of at least 1 year. According to univariate analysis, a localized scalp EEG seizure onset (p < 0.001), a multilobar intracerebral seizure-onset zone (SOZ) (p < 0.001), and an extended SOZ (p = 0.001) were significantly associated with surgical outcome. According to multivariable analysis, the following two independent factors were found: 1) the ability of scalp EEG to localize the seizure onset was a predictor of a favorable postoperative outcome (OR 6.073, 95% CI 2.011–18.339, p = 0.001), and 2) a multilobar SOZ was a predictor of an unfavorable outcome (OR 0.076, 95% CI 0.009–0.663, p = 0.020).CONCLUSIONSThe study findings show that localization at scalp seizure onset and a multilobar SOZ were strong predictors of surgical outcome. These predictors can help to select the better candidates for resective surgery.


Author(s):  
Sunday Azagba ◽  
Lingpeng Shan

Evidence suggests that as immigrants’ length of residence in the host country increases, they may integrate their behavior and norms to align with the new community’s cultural norms. The current study examined e-cigarette use among immigrants in the U.S., and whether the length of residence in the U.S. is associated with e-cigarette use among immigrants compared to the native-born population. Data were drawn from the 2014/15 and 2018/19 Tobacco Use Supplement to the Current Population Survey. Multivariable logistic regression was used to compare differences in e-cigarette use between native-born populations and immigrants, when immigrants’ length of residence in the U.S. was considered. Among immigrants, the prevalence of ever and current e-cigarette use increased significantly from 2.5% and 0.5% in 2014/2015 to 3.2% and 0.8% in 2018/2019, respectively. Multivariable analysis showed that immigrants had significantly lower odds of ever e-cigarette use compared to the mainland-born citizen (0–5 years in the U.S., adjusted Odds Ratio (aOR) 0.57, 95% Confidence Interval (CI) 0.46–0.69; 6–10 years, aOR 0.51, 95% CI 0.41–0.63; 11–20 years, aOR 0.45, 95% CI 0.39–0.53; 20+years, aOR 0.68, 95% CI 0.62–0.76). Similar results were found for current e-cigarette use, with immigrants being less likely to be current users. Findings that e-cigarette use among all immigrants—regardless of years living in the U.S.—was consistently lower than among the native-born population run contrary to the notion that as length of stay increases, health behaviors between immigrants and native populations of the host country become similar.


2021 ◽  
Vol 14 ◽  
pp. 175628482110356
Author(s):  
Lina Zhang ◽  
Huanqin Han ◽  
Xuan Li ◽  
Caozhen Chen ◽  
Xiaobing Xie ◽  
...  

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p < 0.001], and hospital stay [−3 (−5 to −1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.


2021 ◽  
pp. 019459982098435
Author(s):  
Evan J. Patel ◽  
Jamie R. Oliver ◽  
Alec Vaezi ◽  
Zujun Li ◽  
Michael Persky ◽  
...  

Objectives To describe patterns of primary surgical treatments in patients with T4b oral cavity squamous cell carcinoma (OCSCC). Study Design Historical cohort study. Setting National Cancer Database. Methods Review of the National Cancer Database between 2004 and 2017 for all T4b OCSCCs. Only patients with curative treatment methods were included in the survival analysis. Surgical and nonsurgical outcomes were compared by multivariable and propensity score matching analysis. Results A total of 1515 cases of T4b OCSCC were identified. A minority of patients (n = 363, 24.0%) underwent curative treatment; among these, 206 (56.7%) underwent primary surgery. Median length of follow-up was 24 months. The 90-day mortality of patients who underwent surgical treatment was 1.0%. The 2-year survival was higher for patients who underwent surgery + chemoradiotherapy (CRT) as compared with CRT (64.6% vs 45.2%, P < .001). On multivariable analysis, surgery + CRT was associated with longer survival. In a propensity score–matched cohort of 312 patients, 2-year survival remained higher in the surgical group versus the nonsurgical group (59.4% vs 45.5%, P = .02). Among patients who underwent surgery + CRT, there was no difference in 2-year survival between clinical T4a and T4b (59% vs 64.6%, P = .20). Conclusions A minority of patients with T4b OCSCC undergo treatments with curative intent. A subset of patients underwent primary surgical treatment, which was associated with longer survival. The T4b classification might entail a heterogenous group, and further studies in revision of this classification might be justified.


Vascular ◽  
2021 ◽  
pp. 170853812110261
Author(s):  
Daniel Perren ◽  
Lauren Shelmerdine ◽  
Luke Boylan ◽  
Craig Nesbitt ◽  
James Prentis ◽  
...  

Introduction Acute limb ischaemia (ALI) forms a significant part of the vascular surgery workload and carries with it high rates of morbidity and mortality. Anaemia is also common amongst vascular surgical patients and has been linked with poor outcomes in some subgroups. We aimed to assess the frequency of anaemia in patients with ALI and its impact on survival and complications following revascularisation to help direct future efforts to optimise outcomes in this patient group. Methods A retrospective analysis of prospectively collected departmental data on patients undergoing surgical intervention for ALI between 2014 and 2018 was performed. Anaemia was defined as a pre-operative haemoglobin (Hb) of <120 g/L for women and <130 g/L for men. The primary outcome was overall survival, assessed with the Kaplan–Meier estimator, with application of Cox proportional hazard modelling to adjust for confounding covariates. Results There were 158 patients who underwent treatment for ALI: 89 (56.3%) of these were non-anaemic with a mean Hb of 146 (SD = 18.4), and 69 (43.7%) were anaemic with a mean Hb of 106 (SD = 13.4). Anaemic patients had a significantly higher risk of death than their non-anaemic counterparts on univariate analysis (HR = 2.11, 95% CIs, 1.28–3.5, p = 0.0036). There was ongoing divergence in survival up to around 6 months between anaemic and non-anaemic groups. Under the Cox model, anaemia was similarly significant as a predictor of death (HR = 2.15, 95% CIs, 1.17–3.95, p = 0.013), accounting for recorded comorbidities, medication use and blood transfusion. Conclusions Anaemia is a significant and independent risk factor for death following revascularisation for ALI and can be potentially be modified. Vascular surgical centres should ensure they have robust pathways in place to identify and consider treating anaemia. There is scope for further work to assess how to best optimise a patient’s levels of circulating haemoglobin.


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