Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide (EC or HEC) with cyclophosphamide, methotrexate, and fluorouracil (CMF) in 777 women with node-positive (N+) breast cancer (BC): 10-year follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 568-568 ◽  
Author(s):  
E. Azambuja ◽  
M. Paesmans ◽  
C. Bernard-Marty ◽  
M. Beauduin ◽  
A. Vindevoghel ◽  
...  
Keyword(s):  
Cox Regression ◽  
Menopausal Status ◽  
Survival Rates ◽  
Dose Intensity ◽  
Phase Iii ◽  
Open Label ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Primary Hypothesis

568 Background: The purpose of this presentation is to provide an update, with longer follow up data, of the results of this Belgian multicentric trial, which had shown a dose response curve for epirubicin at a median follow up of 4 years (Piccart et al, J Clin Oncol 2001; 19:3103–3110) Methods: In this prospective, open label, randomized trial of the 1990’s, patients aged from 18 to 70 years were stratified by center, 1–3 vs 4 or more nodes, and menopausal status (pre- vs postmenopausal). The primary hypothesis was that HEC could be associated with an increase in event-free survival (EFS) compared with CMF. Patients received CMF (oral cyclophosphamide days 1–14) for six cycles, EC (epirubicin 60 mg/m2, cyclophosphamide 500 mg/m2 day 1 every 3 weeks) for eight cycles or HEC (epirubicin 100 mg/m2, cyclophosphamide 830 mg/m2 day 1 every 3 weeks) for eight cycles. Tamoxifen followed chemotherapy in postmenopausal women with positive or unknown hormone receptor (HR). Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Results: The trial results are now updated, with an actuarial median follow-up of 12.2 years. Using Kaplan-Meier estimation, the 10-year EFS is 55% for patients who received CMF, 48% for EC patients, and 58% for HEC patients. The hazard ratios obtained from Cox regression models (HR) are, for EC vs HEC, 1.30 (95% confidence interval [CI], 1.02 to 1.67, P = .03); for CMF vs HEC, 1.12 (95% CI, 0.87 to 1.44, P = .39); and for CMF vs EC, 1.17 (95% CI, 0.92 to 1.48, P = .21). Kaplan-Meier estimates of the 10-year overall survival rates are 65% for patients who received CMF, 65% for EC patients, and 70% for HEC patients, with no significant differences among the three arms. Conclusions: The short term results of this trial are nicely confirmed at 10 years: in patients unselected for HR or HER-2 status, the dose intensity of epirubicin matters. Analysis in subsets of patients is ongoing, but will be only hypothesis-generating. [Table: see text]

scholarly journals Mortality in Patients with Diabetic Foot Ulcers: Causes, Risk Factors, and Their Association with Evolution and Severity of Ulcer

2020 ◽  
Vol 9 (9) ◽  
pp. 3009
Author(s):  
José Antonio Rubio ◽  
Sara Jiménez ◽  
José Luis Lázaro-Martínez
Keyword(s):  
Diabetic Foot ◽  
Cox Regression ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
History Of

Background: This study reviews the mortality of patients with diabetic foot ulcers (DFU) from the first consultation with a Multidisciplinary Diabetic Foot Team (MDFT) and analyzes the main cause of death, as well as the relevant clinical factors associated with survival. Methods: Data of 338 consecutive patients referred to the MDFT center for a new DFU during the 2008–2014 period were analyzed. Follow-up: until death or until 30 April 2020, for up to 12.2 years. Results: Clinical characteristics: median age was 71 years, 92.9% had type 2 diabetes, and about 50% had micro-macrovascular complications. Ulcer characteristics: Wagner grade 1–2 (82.3%), ischemic (49.2%), and infected ulcers (56.2%). During follow-up, 201 patients died (59.5%), 110 (54.7%) due to cardiovascular disease. Kaplan—Meier curves estimated a reduction in survival of 60% with a 95% confidence interval (95% CI), (54.7–65.3) at 5 years. Cox regression analysis adjusted to a multivariate model showed the following associations with mortality, with hazard ratios (HRs) (95% CI): age, 1.07 (1.05–1.08); HbA1c value < 7% (53 mmol/mol), 1.43 (1.02–2.0); active smoking, 1.59 (1.02–2.47); ischemic heart or cerebrovascular disease, 1.55 (1.15–2.11); chronic kidney disease, 1.86 (1.37–2.53); and ulcer severity (SINBAD system) 1.12 (1.02–1.26). Conclusion: Patients with a history of DFU have high mortality. Two less known predictors of mortality were identified: HbA1c value < 7% (53 mmol/mol) and ulcer severity.

Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21040-21040
Author(s):  
R. Trujillo ◽  
E. Gallego ◽  
A. Márquez ◽  
N. Ribelles ◽  
J. Trigo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Phase Iii ◽  
Rank Test ◽  
Prognostic Effect ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Her 2

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.

KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
Javier Cortes ◽  
David W. Cescon ◽  
Hope S. Rugo ◽  
Zbigniew Nowecki ◽  
Seock-Ah Im ◽  
...  
Keyword(s):  
Cox Regression ◽  
Phase Iii ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Kaplan Meier ◽  
Primary Endpoints ◽  
Immune Mediated ◽  
Locally Recurrent ◽  
Grade 3

1000 Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (ClinicalTrials.gov, NCT02819518) compared pembro + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated locally recurrent inoperable or metastatic TNBC. Methods: Pts with ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel; paclitaxel; or gemcitabine/carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs <1), and prior (neo)adjuvant treatment with same-class chemo (yes vs no). Dual primary endpoints are PFS (RECIST v1.1, blinded independent central review) and OS by tumor PD-L1 expression (CPS ≥10 and ≥1) and in all pts. PFS was estimated using the Kaplan-Meier method. Stratified log-rank tests were used to assess treatment group differences. HR and 95% CIs were based on a stratified Cox regression model. AEs were monitored throughout the study and graded per NCI CTCAE v4.0. Results: As of Dec 11 2019, median follow-up was 17.5 mo for pembro + chemo (n=566) and 15.5 mo for chemo (n=281). Pembro + chemo significantly improved PFS vs chemo alone in pts with CPS ≥10 tumors (Table), meeting one of the protocol-defined primary objectives. Although the boundary for a statistically significant benefit of pembro + chemo in pts with CPS ≥1 tumors was not met and formal testing in ITT was not performed, the pembro treatment effect increased with PD-L1 enrichment (Table). OS follow-up is ongoing. Grade 3-5 treatment-related AE rates were 68.1% with pembro + chemo (2 deaths) vs 66.9% with chemo (0 deaths); rates of grade 3-4 immune-mediated AEs and infusion reactions were 5.5% vs 0%. Clinical trial information: NCT02819518 . Conclusion: Pembro combined with several chemo partners showed a statistically significant and clinically meaningful improvement in PFS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). Pembro + chemo was generally well tolerated, with no new safety concerns. [Table: see text]

DeCIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5500-5500 ◽  
Author(s):  
Ezra E. W. Cohen ◽  
Theodore Karrison ◽  
Masha Kocherginsky ◽  
Chao H Huang ◽  
Mark Agulnik ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Survival Rates ◽  
Phase Iii ◽  
High Survival ◽  
Open Label ◽  
Free Survival ◽  
Prior Therapy ◽  
Distant Failure ◽  
Grade 3

5500 Background: IC is associated with lower distant failure (DF) rates in SCCHN but an improvement in overall survival (OS) has not been validated. The goal of this trial was to determine whether IC prior to chemoradiotherapy (CRT) improves survival compared to CRT alone. Methods: In this phase 3, open-label trial, subjects with pathologically confirmed SCCHN; N2/N3 disease without metastases; no prior therapy; KPS ³ 70%; and intact organ function were randomized to CRT alone (CRT arm) [5 days of D (25 mg/m2), F (600 mg/m2), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9 day break] or to 2 cycles of IC [D (75 mg/m2), P (75 mg/m2), F (750 mg/m2 day 1-5)] followed by the same CRT (IC arm). Primary endpoint was OS. Secondary endpoints included DF free survival, failure pattern, and recurrence-free survival (RFS). 280 subjects provided 80% power to detect a hazard ratio HR=0.5 for OS (a=0.05). Results: 280 subjects were accrued from 2004-09 with minimum follow-up 24 months. Of 142 patients randomized to IC, 91% received 2 cycles and 87% continued to CRT. Treatment adherence during CRT was high for docetaxel and hydroxyurea, but fewer than 75% of the patients received target dose of 5FU in both arms. RT was delivered without major deviations in 94% and 95% of patients on IC and CRT arms, respectively. The most common grade 3-4 toxicities during IC were febrile neutropenia (9%) and mucositis (8%), and during CRT (both arms combined) they were mucositis (45%), dermatitis (19%), and leukopenia (17%). Only grade 3-4 leukopenia and neutropenia rates were significantly higher in IC (p=0.002 and p=0.02, respectively). Table shows efficacy. Conclusions: High survival rates were observed in both arms. Further analysis and follow-up may provide insight into why the significant decrease in DF did not translate into improved OS. [Table: see text]

Relation Between Cereblon Expression and Survival in Patients with Newly Diagnosed Multiple Myeloma Treated with Thalidomide

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3973-3973
Author(s):  
Annemiek Broyl ◽  
Rowan Kuiper ◽  
Mark van Duin ◽  
Bronno van der Holt ◽  
Laila el Jarari ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Hazard Ratios

Abstract Abstract 3973 Introduction: Cereblon (CRBN) expression has been described to be essential for the activity of Thalidomide and Lenalidomide. This suggests that presence and possibly increased level of CRBN expression would be associated with better outcome in Thalidomide/Lenalidomide treated patients. The aim of this study was to evaluate CRBN expression in relation to outcome in patients receiving Thalidomide maintenance. Patients and methods: The HOVON-65/GMMG-HD4 trial is a multi-center, phase III trial, comparing Bortezomib in induction and post-intensification vs. conventional chemotherapy and daily Thalidomide 50 mg for 2 years post-intensification in newly diagnosed MM patients. This trial demonstrated that Bortezomib during induction and maintenance improved CR and achieved superior PFS and OS (Sonneveld et al., JCO, July 16, 2012). Gene expression profiling was performed at the start of the trial by Affymetrix U133 Plus 2.0 GeneChip, and was available for 96 patients which started Thalidomide maintenance. CRBN expression levels were based on a combined value of probe sets 218142_s_at and 222533_at. CRBN expression was validated using real-time PCR. All survival analyses were performed in SPSS, with survival time taken from the start of maintenance. Results: In patients receiving Thalidomide maintenance, increased CRBN expression was significantly associated with longer progression free survival (p=0.005, hazard ratio = 0.7) and longer overall survival (p=0.04, hazard ratio= 0.7). Using Kaplan-Meier analysis for visualization and using the median expression to define high and low expression, a significant separation was found for PFS (Log rank p=0.009) but not for OS (Log rank p=0.13). No association was observed between CRBN expression and PFS/OS after Bortezomib maintenance (PFS, p=0.4, hazard ratio=1.1; OS, p=0.7, hazard ratio=1.1). Multivariate Cox regression analysis was performed using the covariates ISS, CRBN and high-risk cytogenetics, defined as having del(17p) and/or 1q gain and/or t(4;14). Higher CRBN levels remained significantly related to longer PFS (hazard ratio 0.7, p=0.03), but not OS (hazard ratio of 0.8, p=0.3). High-risk cytogenetics and ISS were both significant in both PFS and OS multivariate models, with hazard ratios of 2.8 and 3.6, for high-risk cytogenetics and 2.5 and 5.5, for ISS stage 3, respectively (p=0.0004, p=0.003, high-risk cytogenetics and p=0.01 and p=0.005, ISS stage 3, respectively). Conclusion: These data suggest use of CRBN as a biomarker for thalidomide outcome, but further analysis in other Thalidomide trials is required to validate this finding. Disclosures: Lokhorst: Genmab: Consultancy. Sonneveld:Onyx: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; celgene: Honoraria, Research Funding.

ESPAC-3(v2): A multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA4505-LBA4505 ◽  
Author(s):  
J. Neoptolemos ◽  
M. Büchler ◽  
D. D. Stocken ◽  
P. Ghaneh ◽  
D. Smith ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Bolus Injection ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Open Label ◽  
Treatment Groups ◽  
Significant Difference

LBA4505 Background: Adjuvant 5-FU/FA (ESPAC-1 trial) and GEM (CONKO-001 trial) provide improved survival for patients with resected pancreatic cancer compared to no chemotherapy. The aim of the ESPAC-3 (v2) trial was to compare 5FU/FA vs GEM to identify if either adjuvant chemotherapy was associated with a significantly better survival. Methods: Patients with an R0/R1 resection for pancreatic ductal adenocarcinoma were randomized (stratified for resection margin status and country) <8 weeks of surgery to receive either 5FU/FA (FA, 20 mg/m2, iv bolus injection followed by 5-FU, 425 mg/m2, iv bolus injection given 1–5d every 28 days) or GEM (1,000mg/m2 iv infusion 1d, 8d and 15d every 4 weeks) for 6 months. The primary outcome measure was overall survival; the secondary measures were toxicity, progression free survival and quality of life. 1,030 patients were needed to detect a 10% difference in 2-year survival rates with 90% power. Results: 1,088 patients from 16 countries were randomized from July 2000 to Jan 2007 (5FU/FA = 551, GEM = 537). Median (range) age was 63 (31–85) years; 598 (55%) were men. Median tumor size was 30 (20–350) mm; 384 (35%) were R1 resections; 777 (72%) were node positive; and 263 (25%) were poorly differentiated tumors. Final analysis was carried out on an intention to treat basis with a minimum of 2 years follow-up after 753 (69%) patients had died. Median (IQR) follow-up of 335 alive patients was 34.2 (27.1–43.4) months, equal across treatment groups. Median survival from resection of patients treated with 5FU/FA was 23.0 (95% CI: 21.1, 25.0) months and for patients treated with GEM this was 23.6 (95%CI: 21.4, 26.4) months. Log-rank analysis revealed no statistically significant difference in survival estimates between the treatment groups (c2LR=0.7, p=0.39, HRGEM=0.94 (95%CI: 0.81, 1.08)). There was no significant difference in the effect of treatment across subgroups according to R status (test of heterogeneity c21=0.3, p=0.56). Conclusions: This is the largest adjuvant trial ever conducted for pancreatic ductal adenocarcinoma and showed no significant difference in survival between adjuvant 5FU/FA and adjuvant GEM. [Table: see text]

Randomized phase III study of adjuvant chemotherapy for high-risk, node-negative breast cancer (BC) comparing FAC with FAC followed by weekly paclitaxel: First efficacy analysis of the GEICAM/2003-02 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
Miguel Martin ◽  
Ana Lluch ◽  
Amparo Ruiz ◽  
Manuel Ruiz Borrego ◽  
Agust Barnadas ◽  
...  
Keyword(s):  
High Risk ◽  
Menopausal Status ◽  
Dose Intensity ◽  
Drop Out ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
P Value ◽  
Her2 Positive ◽  
Node Negative

1001 Background: Adjuvant weekly paclitaxel (wP) sequential to anthracyclines improves the outcome of operable node-positive BC patients (pts) [Sparano NEJM 2008, Martin BCRT 2009]; however, most BC pts are currently node-negative at diagnosis. The role of wP in these pts is not well established yet. Methods: Pts aged 18-70, with T1-T3/N0 operable BC and at least one high-risk St Gallen 1998 criteria (size >2 cm, hormone-receptor [HR] negative, grade 2/3, age <35 years,) were eligible. HER2+ pts were allowed, after 792 entered the trial, the study was amended to exclude them. Pts were stratified by site, menopausal status, nodal status diagnostic method (sentinel-node biopsy versus lymphadenectomy) and HR status and randomized to receive FAC x6 (500/50/500 mg/m2 every 3w) or FAC x4→wP x8 (paclitaxel 100 mg/m2 weekly). The primary endpoint was DFS. The trial was designed to detect an absolute 5-y DFS increase of 5% (80% FAC, 85% FAC→wP); a sample size of 1812 evaluable patients (906 per arm) was required to detect this difference (α=0.05, β= 80%). Assuming a drop-out rate of 6%, 1929 pts were required. The first analysis of DFS was planned when a median follow-up of 5 years was reached. Results: Between September 2003 and October 2008, 1925 pts (FAC 974, FAC→wP 951) were randomized. Patient characteristics were well balanced between arms, median age was 50, 73% of pts were HR positive and 9% HER2 positive. 97% of pts with FAC and 85% of pts with FAC→wP completed all treatment as planned. The median dose intensity was 98% with FACx6, 99% with FACx4 and 98% with wP. The most frequent grade 3-4 toxicities (>3% in either arm) with FAC vs FAC→wP were neutropenia (25% vs 22%) with 4% vs 3% of febrile neutropenia, fatigue (3% vs 8%), sensory neuropathy (0 vs 5%), and vomiting (4% in each arm). After a median follow-up of 5.3 years, the proportion of patients disease free is 93% and 90% with FAC→wP and FAC (HR for relapse 0.732, 95% CI: 0.542 to 0.990; log-rank p-value=0.0423). Conclusions: For pts with high-risk node-negative BC, adjuvant FAC→wP was associated with a small but significant improvement in DFS compared with FAC, with manageable toxicity.

scholarly journals ACTR-13. FINAL RESULTS WITH CHEMORADIOTHERAPY FOR ANAPLASTIC OLIGODENDROGLIAL TUMORS FROM NRG ONCOLOGY/RTOG 9402

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi15-vi15
Author(s):  
Andrew Lassman ◽  
Minhee Won ◽  
J Gregory Cairncross ◽  
Edward Shaw ◽  
Lynn Ashby ◽  
...  
Keyword(s):  
Cox Regression ◽  
Predictive Biomarker ◽  
Idh Mutation ◽  
Organ Function ◽  
Oligodendroglial Tumors ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Post Hoc

Abstract BACKGROUND Adding intensive-procarbazine, lomustine, and vincristine (iPCV) to radiotherapy (RT) prolonged progression-free (PFS) and overall survival (OS) for patients with 1p19q codeleted anaplastic oligodendroglial tumors (AOTs); some benefit was also observed for IDH-mutant non-codeleted cases (Cairncross et al 2013, 2014, 2016). Now, 25 years after study activation, we updated survival, further assessed IDH as a predictive biomarker, and are exploring the benefit from vincristine. METHODS Eligible adults (KPS ≥ 60, adequate end-organ function) were randomized to pre-RT iPCV (4 cycles x 6 weeks each) vs. RT alone, stratified by age (< or ≥ 50), KPS (60–70 or ≥ 80), and level of anaplasia. Histology (anaplastic oligodendroglioma/oligo-astrocytoma required) and biomarkers (IDH and 1p19q, post-hoc) were determined centrally. Survival was estimated by Kaplan-Meier and Hazard Ratios (HRs) by Cox-regression. RESULTS Overall (n=289), median follow-up was 16.4 years vs. 11.3 years at last report. In codeleted cases, 40% randomized to iPCV remained alive vs. 53% at last report; 5, 10, and 14 year-PFS and -OS rates were 62%, 50%, 41% and 70%, 57%, 46%, respectively; and iPCV unequivocally prolonged PFS (median 9.8 vs. 2.9 years, HR 0.46, 95% CI 0.3–0.7, p< 0.001) and OS (median 13.2 vs. 7.3 years, HR 0.61, 95% CI 0.40–0.94; p=0.02). With IDH mutation but without codeletion (n=66), iPCV prolonged PFS (median 2.8 vs. 1.9 years, HR 0.58, 95% CI 0.34–0.99, p=0.046); OS was longer with a trend for significance (median 5.5 vs. 3.3 years, HR 0.6, 95% CI 0.34–1.03, p=0.06) on this underpowered exploratory post-hoc analysis. CONCLUSION For codeleted AOTs, long-term analyses confirmed that pre-RT iPCV produced meaningful and significant prolongations of PFS and OS. With IDH mutation but without codeletion, iPCV significantly prolonged PFS and showed a trend for prolonged OS. The value of vincristine is being assessed. Supported by NCI grants U10CA180868, U10CA180822, U24CA196067, and UG1CA189867.

scholarly journals FDG PET biomarkers for prediction of survival in metastatic melanoma prior to anti-PD1 immunotherapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Flaus ◽  
V. Habouzit ◽  
N. De Leiris ◽  
J. P. Vuillez ◽  
M. T. Leccia ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Fdg Pet ◽  
Cox Regression ◽  
Prognostic Score ◽  
Survival Rates ◽  
Risk Groups ◽  
Hazard Ratios ◽  
Prediction Of Survival ◽  
Innovative Therapies

AbstractOur aim was to analyse whether biomarkers extracted from baseline 18F-FDG PET before anti-PD1 treatment contribute to prognostic survival information for early risk stratification in metastatic melanoma. Fifty-six patients, without prior systemic treatment, BRAF wild type, explored using 18F-FDG PET were included retrospectively. Our primary endpoint was overall survival (OS). Total metabolic tumoral volume (MTV) and forty-one IBSI compliant parameters were extracted from PET. Parameters associated with outcome were evaluated by a cox regression model and when significant helped build a prognostic score. Median follow-up was 22.1 months and 21 patients died. Total MTV and long zone emphasis (LZE) correlated with shorter OS and served to define three risk categories for the prognostic score. For low, intermediate and high risk groups, survival rates were respectively 91.1% (IC 95 80–1), 56.1% (IC 95 37.1–85) and 19% (IC 95 0.06–60.2) and hazard ratios were respectively 0.11 (IC 95 0.025–0.46), P = 0.0028, 1.2 (IC 95 0.48–2.8), P = 0.74 and 5.9 (IC 95 2.5–14), P < 0.0001. To conclude, a prognostic score based on total MTV and LZE separated metastatic melanoma patients in 3 categories with dramatically different outcomes. Innovative therapies should be tested in the group with the lowest prognosis score for future clinical trials.

scholarly journals Neutrophil:lymphocyte ratio predicts short-term outcome of COVID-19 in haemodialysis patients

2020 ◽  
Author(s):  
Prisca Mutinelli-Szymanski ◽  
Iulia Hude ◽  
Emilie Merle ◽  
Yannis Lombardi ◽  
Pascal Seris ◽  
...  
Keyword(s):  
Cox Regression ◽  
Term Outcome ◽  
Multicentric Study ◽  
Reactive Protein ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Increased Risk ◽  
And Biological Markers ◽  
Dialysis Facilities

Abstract Background Information regarding coronavirus disease 2019 (COVID-19) in haemodialysis (HD) patients is limited and early studies suggest a poor outcome. We aimed to identify clinical and biological markers associated with severe forms of COVID-19 in HD patients. Methods We conducted a prospective, observational and multicentric study. Sixty-two consecutive adult HD patients with confirmed COVID-19 from four dialysis facilities in Paris, France, from 19 March to 19 May 2020 were included. Blood tests were performed before diagnosis and at Days 7 and 14 after diagnosis. Severe forms of COVID-19 were defined as requiring oxygen therapy, admission in an intensive care unit or death. Cox regression models were used to compute adjusted hazard ratios (aHRs). Kaplan–Meier curves and log-rank tests were used for survival analysis. Results Twenty-eight patients (45%) displayed severe forms of COVID-19. Compared with non-severe forms, these patients had more fever (93% versus 56%, P &lt; 0.01), cough (71% versus 38%, P = 0.02) and dyspnoea (43% versus 6%, P &lt; 0.01) at diagnosis. At Day 7 post-diagnosis, neutrophil counts, neutrophil:lymphocyte (N:L) ratio, C-reactive protein, ferritin, fibrinogen and lactate dehydrogenase levels were significantly higher in severe COVID-19 patients. Multivariate analysis revealed an N:L ratio &gt;3.7 was the major marker associated with severe forms, with an aHR of 4.28 (95% confidence interval 1.52–12.0; P = 0.006). After a median follow-up time of 48 days (range 27–61), six patients with severe forms died (10%). Conclusions HD patients are at increased risk of severe forms of COVID-19. An elevated N:L ratio at Day 7 was highly associated with the severe forms. Assessing the N:L ratio could inform clinicians for early treatment decisions.

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