Survival and prognostic factors in patients with malignant pleural mesothelioma (MPM) treated with neoadjuvant cisplatin- based chemotherapy and extrapleural pneumonectomy (EPP) (SITMP Study)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18061-18061
Author(s):  
V. Mutri ◽  
C. Pinto ◽  
A. Marino ◽  
M. Di Bisceglie ◽  
D. Dell’Amore ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Preoperative Chemotherapy ◽  
Cox Regression ◽  
Objective Response ◽  
Resection Margins ◽  
Extrapleural Pneumonectomy ◽  
Cox Regression Analysis ◽  
Group A ◽  
Group B ◽  
The Impact

18061 Background: The aim of this study is to evaluate the impact on survival of preoperative chemotherapy in potentially resectable MPM and correlations with prognostic factors. Methods: The eligibility criteria were: histologically MPM, stage T1–3N0–2M0, age =75 years, KPS = 80, adequate organ function. A first group of pts (group A) received cisplatin 75 mg/m2 d1 and gemcitabine 1,200 mg/m2 d1,8, every 3 weeks for 4 courses, followed by EPP and by 6 courses of adjuvant chemotherapy with mitoxantrone 10 mg/m2 d1, methotrexate 35 mg/m2 d1 and mitomycin 7 mg/m2 d1, every 3 weeks with mitomycin in alternate cycles. A second group of pts (group B) received cisplatin 75 mg/m2 d1 plus pemetrexed 500 mg/m2 d1 for 4 cycles. In each group, only those pts with metastatic lymph nodes and/or positive resection margins received radiotherapy after EPP. The prognostic factors evaluated were: sex, histotype, stage at diagnosis, clinical objective response. Results: Between February 2000 and December 2006, 32 pts were enrolled (8 group A, 24 group B). Pt characteristics were: 27M (84.4%), 5F (15.6%), median age 64 years (51–72), median KPS 100 (80–100), histological subtype: 27 (84.4%) epithelial, 2 (6.3%) sarcomatous, 3 (9.4%) mixed; IMIG stage: 6 (18.8%) I, 16 (50%) II, 10 (31.2%) III. The clinical response to neoadjuvant chemotherapy was: 10 (31.3%) CR + PR, 16 (50%) SD and 6 (18.7%) PD. Eighteen (56.3%) pts underwent EPP. In the 14 pts who did not undergo EPP: 5 (15.6%) were treated with pleurectomy and 9 (28.1%) were not treated with surgery. Two postoperative deaths (1 contralateral pneumonia and 1 ARDS) occurred after EPP. No pts were treated with radiotherapy after EPP. The estimated median overall survival, 1-year and 2-year survival rates in the pts treated with EPP and not treated with EPP were 20 and 12 months (p=0.468), 60 and 41%, 42 and 20%, respectively. In the multivariate analysis (Cox regression analysis), none of evaluated prognostic factors was significantly associated with an improved OS. Conclusions: These data show that preoperative chemotherapy followed by EPP is a feasible approach, while initial analysis suggests favourable survival. No significant prognostic factors were identified. No significant financial relationships to disclose.

Neoadjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM): An Italian experience with cisplatin-based regimens

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17022-17022
Author(s):  
A. Marino ◽  
C. Pinto ◽  
V. Mutri ◽  
D. Galetta ◽  
M. Di Bisceglie ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Asbestos Exposure ◽  
Vitamin Supplementation ◽  
Resection Margins ◽  
Extrapleural Pneumonectomy ◽  
Small Series ◽  
Group A ◽  
Group B ◽  
The Impact

17022 Background: We have evaluated the feasibility and the impact on survival of two different preoperative chemotherapy regimens in potentially resectable MPM. Methods: Eligibility criteria were: histologically confirmed MPM, stage T1–3 N0–2 M0, adequate organ function, KPS ≥80. A first group of pts (group A) received cisplatin 75 mg/m2 d1 and gemcitabine 1200 mg/m2 d1,8, every 3 weeks for 4 courses, followed by EPP and by 6 courses of adjuvant chemotherapy with mitoxantrone 10 mg/m2 d1, methotrexate 35 mg/m2 d1 and mitomycin 7 mg/m2 d1, every 3 weeks with mitomycin in alternate cycles. A second group of pts (group B) received cisplatin 75 mg/m2 d1 plus pemetrexed 500 mg/m2 d1 with full vitamin supplementation for 4 cycles. In each group, only pts with metastatic lymph nodes and/or positive resection margins underwent radiotherapy after EPP. Results: Twenty-five pts were enrolled from February 2000 to August 2005 (8 in group A and 17 in group B). Pt characteristics were: 21 (84%) males and 4 (16%) females, asbestos exposure in 16 (64%) pts, median age 64 years (range, 51–72), median KPS 100 (80–100), histological subtype: 19 (76%) epithelial, 2 (8%) sarcomatous, 3 (12%) mixed, 1 (4%) unknown; IMIG stage: 6 (24%) I, 14 (56%) II, 5 (20%) III. Clinical response to neoadjuvant chemotherapy consisted of 4 (16%) CR, 2 (8%) PR, 11 (44%) SD, 5 (20%) PD; 3 (12%) pts were not evaluable. The overall response rate (CR + PR) was 24% (95% CI: 9.4 - 45.1). Toxicity was mild in each group. Fourteen (56%) pts have undergone EPP, 5 (20%) pleurectomy and 6 (24%) pts were inoperable. Three postoperative complications and two postoperative deaths (one for controlateral pneumonia and one for ARDS) occurred after EPP. The 1-year survival rate was 60%. Long-term survivors (≥18 months) included 5 pts who had undergone EPP (18, 26, 54, 57 and 63 months) and 2 pts who had undergone pleurectomy (22 and 32 months). Conclusions: These preliminary data, albeit in a small series, suggest that preoperative chemotherapy followed by EPP is a feasible approach to be investigated in larger trials in pts with MPM. No significant financial relationships to disclose.

scholarly journals The Impact of Timing of Dialysis Initiation on Mortality in Patients with Peritoneal Dialysis

2015 ◽  
Vol 35 (7) ◽  
pp. 703-711 ◽  
Author(s):  
Hyung Wook Kim ◽  
Su-Hyun Kim ◽  
Young Ok Kim ◽  
Dong Chan Jin ◽  
Ho Chul Song ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Peritoneal Dialysis ◽  
Renal Disease ◽  
Cox Regression ◽  
Dialysis Initiation ◽  
Cox Regression Analysis ◽  
All Cause Mortality ◽  
Group A ◽  
Group B ◽  
The Impact

BackgroundThe impact of timing of dialysis initiation on mortality is controversial in patients with peritoneal dialysis (PD). In this study, we analyzed the impact of timing of dialysis initiation on mortality in the incident PD population.MethodsIncident patients with PD were selected from the Clinical Research Center (CRC) registry for end-stage renal disease (ESRD), a prospective cohort study on dialysis in Korea. Patients were categorized into 3 groups according to the estimated glomerular filtration rate (eGFR) at the initiation of PD using the Modification of Diet in Renal Disease (MDRD) equation. Group A was defined as eGFR < 5 mL/min/1.73m2, group B as eGFR 5 – 10 mL/min/1.73m2, and group C as eGFR > 10 mL/min/1.73m2. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) of mortality with group B as the reference. The primary outcome was all-cause mortality.ResultsA total of 495 incident PD patients were included. The number of patients in group A was 109, group B was 279, and group C was 107. The median follow-up period was 23 months. Multivariate Cox regression analysis showed that group A had a significantly higher risk of all-cause mortality compared with group B (HR 4.13, 95% confidence interval [CI], 1.55 – 11.03, p = 0.005) after adjustment for age, gender, cause of ESRD, serum albumin level, diabetes mellitus, and cardiovascular disease. There was no significant difference in mortality between group C and group B (HR 1.50, 95% CI, 0.59 – 3.80, p = 0.398) after adjustment for clinical variables.ConclusionAn eGFR < 5 mL/min/1.73m2at the initiation of PD was a significant risk factor for death, while an eGFR >10 mL/min/1.73m2at the initiation of PD was not associated with improved survival compared with an eGFR of 5 – 10 mL/min/1.73m2at the initiation of PD.

The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21587-e21587
Author(s):  
Ting Ye ◽  
Jieying Zhang ◽  
Xinyi Liu ◽  
Mengmei Yang ◽  
Yuhan Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Cox Regression ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

scholarly journals Hemodialysis Adequacy and Its Impact on Long-Term Patient Survival in Demographically, Socially, and Culturally Homogeneous Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Reza Hekmat
Keyword(s):  
Cox Regression ◽  
Patient Survival ◽  
Underlying Disease ◽  
Chronic Hemodialysis ◽  
Historical Cohort ◽  
Cox Regression Analysis ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Iranian Patients

Background. Impact of hemodialysis adequacy on patient survival is extensively studied. The current study compares the survival of chronic hemodialyzed, undocumented, uninsured, Afghan immigrant patients with that of a group of insured Iranian patients matched for underlying disease, age, weight, level of education, marital status, income, and number of comorbid conditions. Methods. Eighty chronic hemodialysis patients (mean age 42.8 ± 10.5 years) entered this historical cohort study in Mashhad, Iran, between January 2012 and January 2015. Half of the patients were undocumented, uninsured, Afghan immigrants (Group A) matched with forty insured Iranian patients (Group B). To compare the survival rate of the two patient groups, Kaplan–Meir survival analysis test was used. Results. Group A patients were underdialyzed with a weekly Kt/V which was significantly less in comparison with that of Group B (1.63 ± 0.63 versus 2.54 ± 0.12, p value = 0.01). While Group A’s number of hemodialysis sessions per week was fewer than that of Group B (1.45 ± 0.56 versus 2.8 ± 0.41, p value = 0.04), the mean of Kt/V in each hemodialysis session was higher in them, in comparison with Group B (1.43 ± 0.25 versus 1.3 ± 0.07, p value = 0.045). In Group B and Group A patients, one-year survival was 70% versus 50%, two-year survival was 55% versus 30%, and three-year survival was 40% versus 20%, respectively (p values = 0.04, 0.02 and 0.04, respectively). In Cox regression analysis, hemodialysis adequacy and uninsurance were factors impacting patients’ survival (OR = 1.193 and 0.333, respectively). Conclusions. Undocumented, uninsured, inadequately hemodialyzed, Afghan patients had a significantly lower one-, two-, and three-year survival as opposed to their Iranian counterparts, probably due to lack of insurance.

scholarly journals P1166DOES PERITONEAL PROTEIN LOSS AFFECT CARDIOVASCULAR MORTALITY OF PERITONEAL DIALYSIS PATIENTS ?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marios Theodoridis ◽  
Stylianos Panagoutsos ◽  
Ioannis Neofytou ◽  
Konstantia Kantartzi ◽  
Efthimia Mourvati ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Peritoneal Dialysis ◽  
Cardiovascular Mortality ◽  
Cox Regression ◽  
Dialysis Patients ◽  
Protein Loss ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Group A ◽  
Group B

Abstract Background and Aims Peritoneal protein loss (PPL) through peritoneal effluent has been a well-recognized detrimental result of peritoneal dialysis (PD). The amount of protein lost will depend on dialysis time, protein size, its serum concentration and other factors including patients’ clinical status. Peritoneal protein loss may be a manifestation of endothelial dysfunction, as with another type of capillary protein leakage, microalbuminuria, a recognized endothelial dysfunction marker. The aim of this study was to retrospectively evaluate the influence of PPL on cardiovascular mortality of peritoneal dialysis patients Method This is a single center retrospective study of 84 PD patients (m=54, f=30) with mean age of 65.2±17 years, mean PD duration of 43.2±24.9 months conducted for the time period from 2006 to 2019 (13 years). The patients were divided into two groups according to the amount of protein excreted during the modified Peritoneal Equilibration Test (PET) procedure using PD solution of 3.86% DW, 2 Lt infusion volume for total time of 4 hours. The total amount of proteins excreted was calculate from PET by multiplying the concentration of proteins at the end of the test with the total volume of PD fluid at the same time. Group A excreted a total amount of proteins &lt; 1.55 gr (median value) at the end of PET test and Group B &gt; 1.55 gr. The cumulative all-cause and cardiovascular survival of the PD patients was calculated by Kaplan Meier while the possible effect of any parameter in survival rates was evaluated by using Cox Regression analysis Results There was not any statistically significant difference between the two groups according to PD duration, age, dialysis adequacy targets, Residual Renal Function(RRF), BMI, ultrafiltration volume during PET and their transport status. The cumulative all-cause survival using Kaplan-Meier analysis revealed no statistically significant deference between the two groups (Log Rank p=0.55) even though mortality risk was adjusted for several factors (Cox Regression). When cardiovascular survival, using Cox Regression analysis, was adjusted for age, sex, Diabetes, PD modality, dialysis Kt/V and RRF we found that Group A (with protein excretion &lt; 1.55 gr) had statistically significant better cardiovascular survival (p=0.029) compared to Group B. We confirm these results while trying to find among the total of our patients the possible risk factors for cardiovascular mortality. Using Cox Regression analysis, the amount of protein excreted during PET procedure and the type of PD solutions (high or low in GDPs) used were statistically significant (p=0.019 and p=0.04 respectively) independent risk factors for cardiovascular survival in our patients. Conclusion These results indicate that protein loss during peritoneal dialysis procedure has negative impact on cardiovascular mortality and survival of PD patients. Additionally, the use of PD solutions with low Glucose Degradation Products (GDPs) and AGEs may improve PD patient’s cardiovascular survival. Randomized interventional studies are encouraged to address the pathological concern of PPL in the future, namely its effects on cardiovascular conditions or its role as marker and effort to reduce PPL using ACE inhibitors or vit D should be considered only if it diminishes cardiovascular morbidity or mortality.

Prognostic factors in patients (pts) with mediastinal nonseminomatous germ cell tumors (MNGCT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Anatoly Bulanov ◽  
Mikhail Fedyanin ◽  
Alexey Tryakin ◽  
Ilya Pokataev ◽  
Tatiana Zakharova ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Mediastinal Tumor ◽  
Cox Regression ◽  
Objective Response ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Good Prognosis ◽  
Cox Regression Analysis ◽  
Prognostic Group

e15585 Background: According to IGCCCG, pts with MNGCT belong to poor prognostic group. But, there are no independent prognostic factors which could determine prognosis in this group of pts. We retrospectively studied prognostic factors in pts with MNGCT. Methods: We analyzed data on 61 pts with MNGCT, who were treated in our department during 1986-2011. Median age was 23 years (range: 18-44). Median follow-up time was 52 months (range 4-180). Biopsy was performed in 35/61 (57.4%) pts before treatment. At the beginning of therapy median AFP was 3,360 IU/ml (range: 1-300,000), HCG – 4.5 mIU/ml (range: 0.1 to 326210), LDH – 791 U/l (range: 249-4,475). Conventional induction chemotherapy (CT): classical BEP regimen – 23 (37.8%) pts, T-BEP – 17 (27.8%) pts, CPOB – 17 (27.8%) pts, accelerated (two-weekly) BEP – 4 (6.6%) pts. After CT, residual tumor was resected in 28 (45.9%) pts. Multivariate Cox regression analysis was performed to determine independent factors, which influenced on overall survival (OS). Results: Marker-negative objective response was revealed in 40/61 (65.6%). Progression disease during induction CT was detected in 21 (34.4%) pts. 5-years OS was 44% for all pts. Multivariate analysis revealed the following independent negative prognostic factors: age ≥ 24 (р=0.08, HR 1.9, 95%CI 0.92-4.1), size of the primary mediastinal tumor ≥ 19 cm (р= 0.03, HR 5.8, 96%CI 1.85-18.67). Median OS hasn’t been reached and 3-year OS was 62% in pts with good prognosis (age < 24 years and/or size of mediastinal tumor < 19 cm) vs. 15 months and 30% in pts with poor prognosis (р=0.02, HR 0.42, 95%CI 0.19-0.87) respectively. Conclusions: Age ≥ 24 and size of the primary mediastinal tumor ≥ 19 cm are independent negative prognostic factors in pts with MNGCT. These factors could be used as strata in clinical trials. However, this tendency has to be confirmed in large series of pts.

CARD: Overall survival (OS) analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel versus abiraterone or enzalutamide.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5569-5569
Author(s):  
Bertrand F. Tombal ◽  
Daniel Castellano ◽  
Gero Kramer ◽  
Jean-Christophe Eymard ◽  
Johann S. De Bono ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Previously Treated ◽  
Alternative Art ◽  
Daily Prednisone ◽  
The Impact

5569 Background: The CARD trial (NCT02485691) compared cabazitaxel vs. an androgen receptor targeted agent (ART; abiraterone/enzalutamide) in mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), in any order. These post hoc analyses assessed OS from various time points and the impact of prognostic factors. Methods: Patients with mCRPC previously treated with docetaxel and progressing ≤ 12 months on prior abiraterone/enzalutamide were randomized 1:1 to cabazitaxel (25 mg/m2 IV Q3W + daily prednisone + prophylactic G-CSF) vs. abiraterone (1000 mg PO + daily prednisone) or enzalutamide (160 mg PO). OS was calculated from date of diagnosis of metastatic disease, date of mCRPC, and start of 1st, 2nd or 3rd life-extending therapy (LET). A stratified multivariate Cox regression analysis assessed the impact of 14 prognostic factors on OS using a stepwise model selection approach with a significance level of 0.10 for entry into the model and 0.05 for removal. Results: In the CARD study (N = 255), median OS was longer with cabazitaxel vs. abiraterone/enzalutamide (13.6 vs 11.0 months; HR 0.64, 95% CI 0.46–0.89; p = 0.008). OS was numerically improved for cabazitaxel vs. abiraterone/enzalutamide when assessed from the time of diagnosis of metastatic disease or mCRPC, or from start of 1st or 2nd LET (Table). In the multivariate analysis, low hemoglobin, high baseline neutrophil to lymphocyte ratio, and high PSA values at baseline were associated with worse OS. In presence of these factors, the OS benefit observed with cabazitaxel versus abiraterone/enzalutamide remained significant (HR 0.63, 95% CI 0.42–0.94, p = 0.022). Conclusions: Cabazitaxel numerically improved OS vs. abiraterone/enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), whatever the time point considered. The robustness of this OS benefit was confirmed by stratified multivariate analysis. Sanofi funded. Clinical trial information: NCT02485691 . [Table: see text]

Enhanced efficacy of anti-VEGFR2/taxane therapy after progression on immune checkpoint inhibition (ICI) in patients (pts) with metastatic gastroesophageal adenocarcinoma (mGEA).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 362-362
Author(s):  
Lionel Aurelien Kankeu Fonkoua ◽  
Sakti Chakrabarti ◽  
Mohamad Bassam Sonbol ◽  
Pashtoon Murtaza Kasi ◽  
Jason Scott Starr ◽  
...  
Keyword(s):  
Cox Regression ◽  
Objective Response ◽  
Chi Square ◽  
Primary Resistance ◽  
Phase 2 Trial ◽  
Fold Reduction ◽  
Group A ◽  
Gastroesophageal Adenocarcinoma ◽  
Group B ◽  
Ecog Ps

362 Background: Most pts with mGEA do not respond to ICI or ramucirumab/paclitaxel (RAM/TAX). Emerging data suggest that ICI may potentiate subsequent therapy (Tx). In KN059 we unexpectedly observed durable responses in 2 pts on RAM/TAX after ICI (PMID 29674442). We examined if ICI impacts efficacy of subsequent RAM/TAX in a larger cohort and explored alterations in the tumor microenvironment. Methods: All pts with mGEA at Mayo Clinic (MN, AZ, FL) who received RAM/TAX (2014-19) were included. We compared best objective response rate (ORR: complete [CR] or partial response [PR]) per RECIST1.1 and overall survival (OS) in pts who received RAM/TAX with (Group A) vs without (Group B) immediately preceding PD-1 blockade. Chi square and multivariate logistic and Cox regression were used. We adjusted for total lines of Tx received and the line of Tx in which RAM/TAX was given, to control for potential differences in the biology of heavily treated pts or those receiving RAM/TAX as 2nd vs 3rd line Tx. We also adjusted for age and ECOG PS. Results: In total 87 pts met inclusion criteria. In the 19 pts (Group A) who received RAM/TAX (usually as 3rd line Tx) after progression on ICI, there was a 77% relative risk reduction of death after initiation of RAM/TAX compared to the 68 pts (Group B) who received RAM/TAX (usually as 2nd line) without preceding ICI (median OS 15.0 vs 7.6 mo; HR 0.23; P < .001). The ORR was also significantly higher (58% vs 18%; P < .001) including the CR rate (16% vs 1%; P = .006). Two CRs in Group A are ongoing (10 - 34 mo). Of note, 95% of Group A pts did not respond to ICI, and all had irRECIST progression on ICI. Immunofluorescent analysis from a responder showed 65-fold reduction (post vs pre-Tx) in intratumoral density of immunosuppressive FOXP3+ Tregs, with preserved density of antitumor CD8+ T cells. Conclusions: Higher than expected efficacy was observed on RAM/TAX when immediately preceded by ICI, suggesting ICI may enhance efficacy of subsequent anti-VEGFR/taxane therapy. This serial immunotherapy combination may be a novel option for pts with primary resistance to ICI and will be tested prospectively in a new randomized phase 2 trial (NCT04069273).

scholarly journals Proactive Infliximab Monitoring Following Reactive Testing is Associated With Better Clinical Outcomes Than Reactive Testing Alone in Patients With Inflammatory Bowel Disease

2018 ◽  
Vol 12 (7) ◽  
pp. 804-810 ◽  
Author(s):  
Konstantinos Papamichael ◽  
Ravy K Vajravelu ◽  
Byron P Vaughn ◽  
Mark T Osterman ◽  
Adam S Cheifetz
Keyword(s):  
Inflammatory Bowel Disease ◽  
Treatment Failure ◽  
Bowel Disease ◽  
Cox Regression ◽  
Drug Discontinuation ◽  
Cox Regression Analysis ◽  
Loss Of Response ◽  
Group A ◽  
Inflammatory Bowel ◽  
Group B

Abstract Background and Aims Reactive testing has emerged as the new standard of care for managing loss of response to infliximab in inflammatory bowel disease [IBD]. Recent data suggest that proactive infliximab monitoring is associated with better therapeutic outcomes in IBD. Nevertheless, there are no data regarding the clinical utility of proactive infliximab monitoring after first reactive testing. We aimed to evaluate long-term outcomes of proactive infliximab monitoring following reactive testing compared with reactive testing alone in patients with IBD. Methods This was a retrospective multicenter cohort study of consecutive IBD patients on infliximab maintenance therapy receiving a first reactive testing between September 2006 and January 2015. Patients were divided into two groups; Group A [proactive infliximab monitoring after reactive testing] and Group B [reactive testing alone]. Patients were followed through December 2015. Time-to-event analysis for treatment failure and IBD-related surgery and hospitalization was performed. Treatment failure was defined as drug discontinuation due to either loss of response or serious adverse event. Results The study population consisted of 102 [n = 70, 69% with CD] patients [Group A, n = 33 and Group B, n = 69] who were followed for (median, interquartile range [IQR]) 2.7 [1.4–3.8] years. Multiple Cox regression analysis identified proactive following reactive TDM as independently associated with less treatment failure (hazard ratio [HR] 0.15; 95% confidence interval [CI] 0.05–0.51; p = 0.002) and fewer IBD-related hospitalizations [HR: 0.18; 95% CI 0.05–0.99; p = 0.007]. Conclusions This study showed that proactive infliximab monitoring following reactive testing was associated with greater drug persistence and fewer IBD-related hospitalizations than reactive testing alone.

scholarly journals Krebs von den Lungen 6 levels in COVID-19 ICU Patients are Associated with Mortality

2021 ◽  
Author(s):  
Giuliana Scarpati ◽  
Daniela Baldassarre ◽  
Graziella Lacava ◽  
Filomena Oliva ◽  
Gabriele Pascale ◽  
...  
Keyword(s):  
Cox Regression ◽  
Icu Patients ◽  
Cox Regression Analysis ◽  
Alveolar Epithelial ◽  
Type Ii Pneumocytes ◽  
Group A ◽  
Predictive Role ◽  
Fraction Of Inspired Oxygen ◽  
Group B

Rationale Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Elevated circulating levels of KL-6 may denote disorder of the alveolar epithelial lining. Objective Aim of this study was to verify if KL-6 values may help to risk stratify and triage severe COVID-19 patients. Methods We performed a retrospective prognostic study on 110 COVID-19 ICU patients, evaluating the predictive role of KL-6 for mortality. Measurements and Main Results The study sample was divided in two groups related according to the median KL-6 value [Group A (KL-6 lower than the log-transformed median (6.73)) and Group B (KL-6 higher than the log-transformed median)]. In both linear and logistic multivariate analyses, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) was significantly and inversely related to KL-6. Death rate was higher in group B than in group A (80.3 versus 45.9%) (p<0.001), Accordingly, the Cox regression analysis showed a significant prognostic role of KL-6 on mortality in the whole sample as well as in the subgroup with SOFA lower than its median value. Conclusions At ICU admission, KL-6 serum level was significantly lower in the survivors group. Our findings shown that, in severe COVID19 patients, elevated KL-6 was strongly associated with mortality in ICU.

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