scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

Current treatments, determinants of use, and survival for patients with hepatoma in the United States from 1998–2002

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4138-4138
Author(s):  
A. B. Siegel ◽  
R. McBride ◽  
D. Hershman ◽  
R. S. Brown ◽  
J. Emond ◽  
...  
Keyword(s):  
Tumor Size ◽  
Proportional Hazards ◽  
Case Series ◽  
Tumor Grade ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Data Set ◽  
Cox Proportional Hazards Models ◽  
Highly Correlated ◽  
The Impact

4138 Background: Multiple case series have described the use of current therapies for hepatocellular carcinoma (HCC), but recent estimates of treatment utilization in the general population and the impact of various treatments on survival are not known. Methods: We first identified 2898 adults diagnosed with HCC with known tumor size and stage in the Surveillance, Epidemiology, and End-Results Program (SEER), from 1998–2002. Treatment was categorized as transplant, resection, ablation, or none of these. We created a second data set of 1856 HCC patients who were potentially operable, as defined by SEER. We used these patients to construct Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: The median age of the larger cohort at HCC diagnosis was 62 (range:18–96). Approximately 42% were white, 32% Asian, 16% Hispanic, and 10% African American. Overall, 10% received a transplant, 18% resection, 8% ablation, and 65% none of these. Only 5% of African Americans with HCC received a transplant, versus 12% of whites, 10% of Hispanics, and 8% of Asians. Asians were most likely to receive resection (24%) and ablation (9%), and least likely to have non-surgical treatment (60%). Using the restricted cohort, improved survival in the multivariate analysis was seen with later year of diagnosis, younger age, female sex, Asian race, smaller tumor size, lower tumor grade, and localized disease. Treatment was highly correlated with survival. This was greatest in the transplanted group (1, 3, and 5-year survivals 93%, 79%, and 71%), followed by resection (70%, 45%, and 29%), and ablation (71%, 33%, and 18%). The non-surgical group had poor survival (33%, 9%, and 0%). Conclusions: Transplantation yields excellent survival on a population scale, similar to reported series, and resection gives relatively good outcomes as well. Asians are more likely to be resected and ablated than other groups. They also had better survival than other groups, perhaps due to underlying etiology of HCC (hepatitis B) and better preserved liver function. No significant financial relationships to disclose.

scholarly journals P109 Impact of ethnicity on colorectal cancer incidence in a cohort of colitis-associated dysplasia patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S201-S202
Author(s):  
M Kabir ◽  
K Curtius ◽  
P Kalia ◽  
I Al Bakir ◽  
C H R Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Racial Differences ◽  
Proportional Hazards ◽  
Hazard Analysis ◽  
Cox Proportional Hazards ◽  
Time Interval ◽  
Low Grade ◽  
Kaplan Meier ◽  
The Impact

Abstract Background Racial disparities in inflammatory bowel disease (IBD) phenotypic presentations and outcomes are recognised. However, there are conflicting data from Western population-based cohort studies as to whether racial differences in colitis-associated colorectal cancer (CRC) incidence exists. To our knowledge this is the first study to investigate the impact of ethnicity on the natural history of dysplasia in ulcerative colitis (UC). Methods We performed a retrospective multi-centre cohort study of adult patients with UC whose first low-grade dysplasia (LGD) diagnosis within the extent of colitis was made between 1 January 2001 and 30 December 2018. Only patients with at least one follow-up colonoscopy or colectomy by 30 August 2019 were included. The study end point was time to CRC or end of follow-up. Statistical differences between groups were evaluated using Mann-Whitney U tests and Chi-squared tests. Survival analyses were performed using Kaplan-Meier estimation and multivariate Cox proportional hazards models. Results 408 patients met the inclusion criteria (see Figure 1 for patient and clinical demographics). More patients from a Black or Asian (BAME) background progressed to CRC [13.4% vs. 6.4%; p=0.036] compared to their White Caucasian counterparts, despite having surveillance follow-up. Figure 2 displays Kaplan-Meier curves demonstrating the probability of remaining CRC-free after LGD diagnosis and categorised by ethnicity. BAME patients were more likely to have moderate-severe inflammatory activity on colonic biopsy within the 5 preceding years [42.0% vs. 28.9%; p=0.023], but no significant differences in medication use and a longer median time interval from LGD diagnosis to colectomy date [32 months vs. 11 months; p=0.021]. After adjusting for sex, age and UC duration at time of LGD diagnosis and presence of moderate-severe histological inflammation, being Black or Asian was a predictive factor for CRC progression on multivariate Cox proportional hazard analysis [HR 2.97 (95% CI 1.22 – 7.20); p = 0.016]. However, ethnicity was no longer predictive of CRC progression on sub-analysis of the 317 patients who did not have a colectomy during the follow-up period. Conclusion In this UK multi-centre cohort of UC surveillance patients diagnosed with LGD, delays in receiving cancer preventative colectomy may contribute to an increased CRC incidence in certain ethnic groups. Further work is required to elucidate whether these delays are related to institutional factors (e.g. inequity in the content of decision-making support given or access to healthcare) or cultural factors.

scholarly journals Clinical Outcomes of Patients with Combined Idiopathic Pulmonary Fibrosis and Emphysema in the IPF-PRO Registry

Lung ◽  
2022 ◽  
Author(s):  
Hyun J. Kim ◽  
Laurie D. Snyder ◽  
Megan L. Neely ◽  
Anne S. Hellkamp ◽  
David L. Hotchkin ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Baseline Variable ◽  
Former Smokers ◽  
The Impact ◽  
Baseline Covariates

Abstract Purpose To assess the impact of concomitant emphysema on outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods The IPF-PRO Registry is a US registry of patients with IPF. The presence of combined pulmonary fibrosis and emphysema (CPFE) at enrollment was determined by investigators’ review of an HRCT scan. Associations between emphysema and clinical outcomes were analyzed using Cox proportional hazards models. Results Of 934 patients, 119 (12.7%) had CPFE. Compared with patients with IPF alone, patients with CPFE were older (median 72 vs 70 years); higher proportions were current/former smokers (88.2% vs 63.7%), used oxygen with activity (49.6% vs 31.9%) or at rest (30.8% vs 18.4%), had congestive heart failure (13.6% vs 4.8%) and had prior respiratory hospitalization (25.0% vs 16.7%); they had higher FVC (median 71.8 vs 69.4% predicted) and lower DLco (median 35.3 vs 43.6% predicted). In patients with CPFE and IPF alone, respectively, at 1 year, rates of death or lung transplant were 17.5% (95% CI: 11.7, 25.8) and 11.2% (9.2, 13.6) and rates of hospitalization were 21.6% (14.6, 29.6) and 20.6% (17.9, 23.5). There were no significant associations between emphysema and any outcome after adjustment for baseline variables. No baseline variable predicted outcomes better in IPF alone than in CPFE. Conclusion Approximately 13% of patients in the IPF-PRO Registry had CPFE. Physiologic characteristics and comorbidities of patients with CPFE differed from those of patients with IPF alone, but the presence of emphysema did not drive outcomes after adjustment for baseline covariates. Trial registration ClinicalTrials.gov, NCT01915511; registered August 5, 2013.

More II It than Meets the Eye: Outcomes After Single-Fraction Stereotactic Radiosurgery in a Case Series of Low-Grade Arteriovenous Malformations

2019 ◽  
Author(s):  
Christopher S Graffeo ◽  
Michael J Link ◽  
Scott L Stafford ◽  
Yolanda I Garces ◽  
Robert L Foote ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Proportional Hazards ◽  
Case Series ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
Single Fraction ◽  
Kaplan Meier ◽  
Radiation Induced ◽  
Martin Grade

Abstract BACKGROUND Surgical resection is typically cited as the optimal treatment of patients with Spetzler-Martin Grade I-II arteriovenous malformation (AVM). OBJECTIVE To report our experience with single-fraction stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I-II AVM. METHODS A prospectively maintained registry was reviewed for patients with nonsyndromic Spetzler-Martin Grade I-II AVM having SRS from 1990 to 2011. Patients with <24 mo of follow-up or prior radiotherapy/SRS were excluded, resulting in a study population of 173 patients. Actuarial analysis was performed using the Kaplan-Meier method, and Cox proportional hazards modeling was performed with excellent outcomes (obliteration without new deficits) as the dependent variable. RESULTS Median post-SRS follow-up was 68 mo (range, 24-275). AVM obliteration was achieved in 132 (76%) after initial SRS. Eleven additional patients achieved obliteration after repeat SRS for an overall obliteration rate of 83%. The rate of obliteration was 60% at 4 yr and 78% at 8 yr. Post-SRS hemorrhage occurred in 7 patients (4%), resulting in 3 minor deficits (2%) and 1 death (<1%). Radiation-induced complications occurred in 5 patients (3%), resulting in minor deficits only. One hundred and thirty-seven patients (79%) had excellent outcomes at last follow-up. CONCLUSION SRS is a safe and effective treatment for patients with Spetzler-Martin Grade I-II AVM. Selection bias is likely a contributing factor to explain the superior outcomes generally noted in reported series of microsurgery for patients with low grade AVM.

Efficacy of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and baseline (BL) comorbidities (CM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5023-5023 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Stephane Oudard ◽  
Boris A. Hadaschik ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Proportional Hazards Models ◽  
Castration Resistant ◽  
Cox Proportional Hazards Models ◽  
The Impact ◽  
Clinical Trial Information

5023 Background: The addition of APA to ongoing ADT in pts with nmCRPC significantly prolonged metastasis-free survival (MFS), time to symptomatic progression (SymProg), and second progression-free survival (PFS2) in SPARTAN. We assessed the impact of APA on these end points in pts with or without BL CM. Methods: Using Cox proportional hazards models, treatment effect of APA was evaluated in SPARTAN pts with CM at BL, stratifying by the presence of BL diabetes/hyperglycemia (D/H), cardiovascular disease (CVD), hypertension (HTN), and renal insufficiency (RI). Results: Of 1207 SPARTAN pts, 1062 (88%) had ≥ 1 BL CM, including 703/806 (87%) APA pts and 359/401 (90%) PBO pts. A total of 226 (19%), 398 (33%), 798 (66%), and 774 (64%) pts had D/H, CVD, HTN, and RI, respectively; 323 (27%), 412 (34%), 259 (21%), and 68 (6%) pts had 1, 2, 3, and 4 CM, respectively. Incidence of CM was balanced between arms. Pts with CM were older than pts with no CM (median age, 75 vs 69 yrs, APA; 74 vs 69 yrs, PBO). MFS, SymProg, and PFS2 benefit with APA was significant in all CM subgroups, except PFS2 for pts with D/H (Table) and regardless of the number of CM. The incidence of any treatment-emergent AE was balanced between pts with and without CM. AEs with APA were not affected by any CM. Clinical trial information: NCT01946204. Conclusions: The benefit of APA + ongoing ADT in pts with nmCRPC was maintained in pts with D/H, CVD, HTN, and RI. The safety profile of APA was not affected by any CM.[Table: see text]

Impact of systemic corticosteroids for cutaneous immune-related adverse events on survival outcomes in patients with advanced cancer: A retrospective cohort study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14523-e14523
Author(s):  
Jaewon Yoon ◽  
Leah L. Thompson ◽  
Nira A. Krasnow ◽  
Michael Chang ◽  
Edward Li ◽  
...  
Keyword(s):  
Adverse Events ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Survival Outcomes ◽  
Infection Rates ◽  
Medical Reason ◽  
Systemic Corticosteroids ◽  
Impact On Survival ◽  
The Impact

e14523 Background: Cutaneous immune-related adverse events (cirAE) may disrupt immune-checkpoint inhibitor (ICI) therapy. Current guidelines recommend systemic corticosteroids (SCS) for moderate to severe cirAE, but SCS-associated complications and their impact on survival remain poorly understood. We therefore investigated the impact of SCS exposures on infectious complications and survival outcomes among patients with cirAE. Methods: We retrospectively reviewed the medical records of patients who initiated anti-programmed death-1/ligand-1 (PD-1/PDL-1) and/or anti-cytotoxic-T-lymphocyte-4 (CTLA-4) ICI therapy between 1/1/16-3/8/19 with confirmed cirAE, obtaining oncologic history, clinical features, SCS exposures, infection rates, and survival outcomes. SCS exposures were categorized by indication (cirAE, other immune-related adverse event, other medical reason) and dosage in prednisone equivalents (low, ≤7.5mg/day for ≥2 months; moderate, > 7.5mg/day for ≥2 months; high, ≥1mg/kg/day for ≥1 week). Infection rates were compared among patients treated with SCS for initial cirAE and those with no SCS exposures for any indication. Cox proportional hazards (CPH) models adjusted for age, sex, and covariates with P <0.05 were used to assess relationships between SCS for first cirAE episode, progression-free survival (PFS) and overall survival (OS). Results: 358 patients developed cirAE (median age 64 years, 40.5% female, 41.9% melanoma). 50 (14.0%) patients received SCS for initial cirAE, 192 (53.6%) received SCS for another indication, and 116 (32.4%) had no SCS exposures. Patients who received SCS for initial cirAE had higher median rash severity (Common Terminology Criteria for Adverse Events grade 3 vs. 1, P< 0.001) and were more likely to be hospitalized for cirAE management (20.0% vs. 1.9%, P< 0.001) than those who did not receive SCS. SCS delivery for initial cirAE was predominantly at low doses (n = 42, 84.0%). Infection rates were higher in patients who received SCS for initial cirAE than those with no SCS exposures for any indication (34.0% vs. 19.8%). Most infections in both groups required systemic therapy (88.2% vs. 95.7%). In multivariate models adjusted for age, sex, and SCS exposures by indication and dosage, patients who received SCS for initial cirAE and those who did not had similar PFS (HR 0.7, CI 0.4-1.3, P= 0.287) and OS (HR 3.0, CI 0.3-35.3, P =0.380). Conclusions: We observed higher rates of infection than previously reported among both patients who did and did not receive SCS for initial cirAE. Despite the theoretical risk of SCS impeding the anti-tumor response, we found no relationship between SCS for initial cirAE and PFS/OS. Collectively, these findings suggest that with appropriate management, low-dose SCS may be safely administered for cirAE without significant impact on survival outcomes.

scholarly journals Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1040
Author(s):  
Valérie Gounant ◽  
Michael Duruisseaux ◽  
Ghassen Soussi ◽  
Sylvie Van Hulst ◽  
Olivier Bylicki ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Cox Proportional Hazards ◽  
Poor Performance Status ◽  
Low Grade ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models

Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

Clinical and pathological risk factors for worse stage and mortality of eyelid and periocular squamous cell carcinoma

2021 ◽  
pp. bjophthalmol-2020-317546
Author(s):  
Yingxiu Luo ◽  
Huifang Chen ◽  
Shengfang Ge ◽  
Yamin Rao ◽  
Jie Yu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Squamous Cell ◽  
Distant Metastasis ◽  
Regression Models ◽  
Proportional Hazards ◽  
Case Series ◽  
Cox Proportional Hazards ◽  
Retrospective Case ◽  
T Stage ◽  
Disease Specific

BackgroundThe clinical and pathological risk factors for worse T stage and prognosis in eyelid and periocular squamous cell carcinomas (SCCs) remain unclear. P63 was reported to predict a worse prognosis in other SCCs; however, this correlation was not validated in eyelid and periocular SCCs.MethodsWe reported on a retrospective case series of 85 consecutive patients with eyelid and periocular SCCs from 1995 to 2019. Cox proportional hazards regression models and logistic regression models were applied for risk factor analysis.ResultsThirty-nine (45.8%) patients were diagnosed with T4 SCCs. Four (5.1%) patients developed nodal metastasis, and five (6.4%) patients developed distant metastasis during the follow-up. 2-year and 5-year disease-specific survival rates were 95.3% and 86.4%, respectively. Poorly or moderately differentiated eyelid and periocular SCCs were associated with worse T stage (p=0.001; p=0.008). Poor differentiation was associated with a higher risk of recurrence (p=0.024). Disease-specific death was more common in patients with T4 stage SCCs (p=0.038, HR=9.05). P63 expression was more common in patients with T3c or worse stage (p=0.008, OR=3.77). P63 expression alone was associated with worse differentiation (p=0.029), higher risk of perineural invasion (p=0.042, OR=4.61) and metastasis (p=0.009, HR=3.99). P63 expression (p=0.012, HR=7.80), coexpression of P63 and Ki67 (p=0.007, HR=9.21) and distant metastasis (p=0.001, HR=11.23) were associated with disease-specific death.ConclusionPatients presented with more aggressive orbital invasion features and a higher rate of distant metastasis in this cohort. P63 and coexpression of Ki67 predicted a worse stage, differentiation and prognosis, including metastasis and death due to disease.

Impact of chemoradiotherapy on PD1/PDL1 expression and clinical outcomes in gastroesophageal cancers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4031-4031
Author(s):  
Arsen Osipov ◽  
Quanlin Li ◽  
Shant Thomassian ◽  
Lakshmanan Annamalai ◽  
Jennifer Holmes Yearley ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Cox Proportional Hazards ◽  
Gastrointestinal Malignancies ◽  
Expression Levels ◽  
Gastric Cancer Patients ◽  
The Impact

4031 Background: Expression of the immune modulating proteins, programmed death receptor-1 (PD1) and its ligand (PDL1), in gastrointestinal malignancies is associated with poor prognosis. PD1/PDL1 expression levels have also been identified as predictors of response to checkpoint inhibition. Minimal data is available on how expression of PD1 and PDL1 is influenced by chemoradiotherapy (CRT). In this study, we investigated the relationship between PDL1/PD1 expression, CRT, and clinical outcomes in gastroesophageal (GE) cancer. Methods: With IRB approval, we identified 28 patients with gastric cardia or GE junction tumors who underwent neoadjuvant standard CRT followed by surgical resection. Pre-CRT biopsies and post-CRT surgical specimens were analyzed using quantitative immunohistochemistry for the expression of PDL1 and PD1. Samples were categorized as trace-low (TL) or moderate-high (MH) expressors of PDL1 and PD1. The impact of these and other clinical and pathologic variables on overall survival (OS) was assessed using multivariate cox proportional hazards modeling. Co-expression of PDL1 and PD1 in matched samples was determined by regression analysis. Results: Following CRT, PDL1 and PD1 expression increased in 54% and 32% of patients, respectively. On multivariate analysis, patients with MH expression of PD1 after CRT irrespective of pre-CRT expression levels had a significant decrease in OS compared to those with TL expression (median survival 23.1 vs 74.1 months; HR,3.31; CI,1.05-10.35; p = 0.039). In patients with gastric confined tumors, an increase in PD1 expression from TL to MH after CRT was associated with significantly lower OS rates (p = 0.003). Regression analysis of PD1 to PDL1 was significant (p < 0.01) both before and after CRT, with a correlation coefficient of 0.34 in pre-CRT and 0.49 in post-CRT specimens. Conclusions: Elevated expression of PD1 is associated with poor OS in patients with GE cancer. Neoadjuvant CRT upregulates both PDL1 and PD1. In gastric cancer patients, this led to significantly worse survival. These data identify potential mechanisms of resistance and suggest a role for checkpoint inhibitors in combination with CRT.

scholarly journals Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 254 ◽  
Author(s):  
Caroline Derrick ◽  
P. Brandon Bookstaver ◽  
Zhiqiang K. Lu ◽  
Christopher M. Bland ◽  
S. Travis King ◽  
...  
Keyword(s):  
Cohort Study ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Bloodstream Infections ◽  
Cox Proportional Hazards ◽  
Third Generation ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Definitive Therapy ◽  
The Impact

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51–1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

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