Prolonged Administration of the Telomerase Vaccine GRNVAC1 Is Well Tolerated and Appears to Be Associated with Favorable Outcomes In High-Risk Acute Myeloid Leukemia (AML)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2190-2190 ◽  
Author(s):  
H. Jean Khoury ◽  
Robert H. Collins ◽  
William Blum ◽  
Lori Maness ◽  
Patrick Stiff ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Disease Free Survival ◽  
Catalytic Subunit ◽  
Patient Specific ◽  
Major Protein ◽  
Intermediate Risk ◽  
Prolonged Administration ◽  
Early Relapse ◽  
Risk Of Relapse

Abstract Abstract 2190 Background: Telomerase activity in leukemic blasts is frequently increased in high-risk AML patients, and the major protein catalytic subunit of telomerase (hTERT) includes immunogenic epitopes which can stimulate generation of hTERT-specific cytotoxic T cells. Methods: We evaluated the feasibility, safety, and immunologic effects of telomerase catalytic subunit (hTERT)-expressing autologous dendritic cells (DC) in adult AML patients. GRNVAC1 (VAC1) was produced at a central facility from patient-specific leukapheresis harvests. Immature DCs from monocyte-enriched PBMCs were electroporated with an mRNA construct encoding hTERT and a lysosomal targeting sequence (LAMP-1). Further culture with cytokines induced a mature DC phenotype. AML patients were eligible if in CR1 and with intermediate or high risk cytogenetics or in CR2. PBMCs were harvested after induction, and before or after completion of planned consolidation cycles. Patients in ongoing CR or early relapse (<20% marrow blasts) were vaccinated. Vials of VAC1 containing 1 × 107 cells were administered by intra-dermal injections weekly × 6, followed by 4 weeks off, then as boost vaccinations every other week × 6. In cases where additional vials were available, injections could then continue on a q28 day extended boost schedule. This abstract summarizes safety of administering VAC1 up through the extended boost schedule. Results: Between September 2007 and December 2009, 33 patients with a median age 61yrs (range, 30–75) were enrolled and leukapheresed. 21 patients received VAC1 vaccinations, 19 in CR (16 in CR1 and 3 in CR2) and 2 in early relapse. Eight of 16 in CR1 were at intermediate risk of relapse and 8 were at high risk of relapse. A median of 17 (6-32) vaccinations were administered to those 19 patients. VAC1 was well tolerated with no toxicities with the exception of one patient who developed ITP after 6 vaccinations. Local transient erythema at the site of injection was common in all patients. With a median follow-up of 10.5 months (range, 1.2–27.2) months, 4/19 relapsed and 7 continue to receive VAC1. The Kaplan-Meier estimate of disease free survival (DFS) at 12 months, measured from beginning with the first vaccination of VAC1, was 79% for the 19 CR patients (95% CI: 52%-91%), 75% (31%-93%) for the eight patients in the intermediate risk group, and 81% for the 11 patients in the high risk group. Median DFS was not reached. Conclusions: Prolonged administration of VAC1, up to 32 vaccinations (the maximum number administered so far), is well tolerated in patients with AML, and associated with favorable DFS, especially in high-risk patients. Disclosures: DiPersio: Genzyme: Honoraria.

Association of pathological response to neoadjuvant pembrolizumab with tumor PD-L1 expression and high disease-free survival (DFS) in patients with resectable, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6006-6006
Author(s):  
Trisha Michel Wise-Draper ◽  
Vinita Takiar ◽  
Michelle Lynn Mierzwa ◽  
Keith Casper ◽  
Sarah Palackdharry ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Disease Free Survival ◽  
Immune Checkpoint Blockade ◽  
Skin Wound ◽  
High Risk Group ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Positive Margins ◽  
Post Surgery

6006 Background: Patients with resected HNSCC, with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year DFS of 65% and 69%, respectively. Immune checkpoint blockade improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiotherapy (RT) synergizes with anti-PD-1. Therefore, we administered the PD-1 inhibitor pembrolizumab (pembro) pre- and post-surgery with adjuvant RT +/- cisplatin in patients with resectable, locoregionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093). Methods: Eligible patients received pembro (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembro (q3 wks x 6 doses) was administered with RT (60-66Gy) with or without weekly cisplatin (40mg/m2 X 6) for patients with high-risk and intermediate-risk features, respectively. The primary endpoint was 1-year DFS estimated by Kaplan Meier curves. Safety was evaluated by CTCAE v5.0. Pathological response (PR) to neoadjuvant pembro was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE), defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. PR was classified as no (NPR, < 20%), partial (PPR, ≥20% and < 90%) and major (MPR, ≥90%). Tumor PD-L1 immunohistochemistry was performed with 22c3 antibody and reported as combined positive score (CPS). Results: Ninety-two patients were enrolled. Seventy-six patients received adjuvant pembro and were evaluable for DFS. Patient characteristics included: median age 58 (range 27 – 80) years; 32% female; 88% oral cavity, 8% larynx, and 3% human papillomavirus negative oropharynx; 86% clinical T3/4 and 65% ≥2N; 49 (53%) high-risk (positive margins, 45%; ECE, 78%); 64% (44/69 available) had PD-L1 CPS ≥1. At a median follow-up of 20 months, 1-year DFS was 67% (95%CI 0.52-0.85) in the high-risk group and 93% (95%CI 0.84-1) in the intermediate-risk group. Among 80 patients evaluable for PR, TE scoring resulted in 48 NPR, 26 PPR and 6 MPR. Patients with PPR/MPR had significantly improved 1-year DFS when compared with those with NPR (100% versus 68%, p = 0.01; HR = 0.23). PD-L1 CPS ≥ 1 was not independently associated with 1-year DFS, but was highly associated with MPR/PPR (p = 0.0007). PPR/MPR in PD-L1 CPS < 1, ≥1 and ≥20, were estimated as 20, 55 and 90%, respectively. Grade ≥ 3 adverse events occurred in 62% patients with most common including dysphagia (15%), neutropenia (15%), skin/wound infections (10%), and mucositis (9%). Conclusions: PR to neoadjuvant pembro is associated with PD-L1 CPS≥1 and high DFS in patients with resectable, local-regionally advanced, HNSCC. Clinical trial information: NCT02641093.

Full Donor T Cell Chimerism Predicts Transplant Outcomes In High Risk AML But Not In Intermediate Risk AML After a T-Deplete Alemtuzumab Conditioned Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5545-5545
Author(s):  
Amy Gudger ◽  
Vidhya Murthy ◽  
Duncan J Murray ◽  
Ben Bailiff ◽  
Maria Mushkbar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
T Cell ◽  
High Risk ◽  
Risk Group ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Donor Chimerism ◽  
Number Of Patients

Abstract Reduced intensity conditioning (RIC) T-deplete regimens are now widely used as a platform to deliver a potentially curative T cell mediated graft-versus-leukaemia (GVL) effect in patients with haematological malignancies. T cell chimerism has been shown to correlate with the risk of both GVHD and disease relapse in T replete RIC AML allografts but it remains unclear whether such a correlation exists in patients undergoing an alemtuzumab based allograft for intermediate and high risk AML. We have therefore correlated T cell chimerism on D+60 and D+180 in 43 patients undergoing an alemtuzumab based RIC allograft for AML(high risk=20, intermediate risk=23) in CR1 with transplant outcomes. The conditioning used was Fludarabine 30mg/m2 for 5 days, Melphalan 140mg/m2 for 1 day and Alemtuzumab 30mg IV for 1 day for sibling transplants and 50mg IV over 2 days for unrelated donor transplants. The median age of the patients was 51 years (range 42-57 years) and median follow up was 45 months (range 6 – 108 months).18 patients received a graft from a sibling donor and 25 from an unrelated fully matched donor. The 3 year overall survival was 53% on the intermediate risk group and 40% on the high risk group. Overall 31% of patients relapsed in both groups. T cell full donor chimerism at D+60 and D+180 was significantly associated with better overall survival (52 months vs 18months p:0.04), 2 years disease free survival of (53% vs 32% p:0.03) and higher incidence (85%) of acute GvHD (p:0.01) and chronic GvHD(p:0.02) in the high risk AML group on both univariate and multivariate analysis. In the intermediate risk group though full donor chimerism was associated with improved disease survival on univariate analysis but this wasn’t confirmed on multivariate analysis and this was likely secondary to the small number of patients. In both univariate and multivariate analysis patients with full donor chimerism at 60 days were almost 80% more likely to have acute GVHD than patients with fully donor chimerism (p=0.04) and patients with full donor chimerism at D+180 were almost 85% more likely to achieve chronic GvHD(p:0.02). Preemptive DLI infusion for mixed chimerism post D+180 was given to patients without prior severe GvHD after stopping Ciclosporin and was associated with improved disease free survival and a trend for improved overall survival for both risk groups by potentially augmenting the GvL effect. The 2 year incidence of graft-versus-host disease post DLI was only 29%. Although conclusions of our study were limited by the small number of patients included, the high risk AML group of patients seems to benefit from acquisition of full donor T cell chimerism. In the intermediate risk group this effect was not demonstrated although probably a higher number of patients with molecular risk stratification is needed. Disclosures: No relevant conflicts of interest to declare.

Predictive Value of Gross Extranodal Extension for Differentiated Thyroid Carcinoma Persistence/Recurrence

2021 ◽  
pp. 019459982110231
Author(s):  
Ying Kou ◽  
Guohua Shen ◽  
Zhuzhong Cheng ◽  
Anren Kuang
Keyword(s):  
High Risk ◽  
Thyroid Carcinoma ◽  
Risk Group ◽  
Differentiated Thyroid Carcinoma ◽  
Individual Risk ◽  
Intermediate Risk ◽  
Entire Cohort ◽  
Gene Group ◽  
Extranodal Extension ◽  
Disease Persistence

Objective We systematically investigated the predictive value of gross extranodal extension (gENE) for differentiated thyroid carcinoma persistence/recurrence. Study Design Retrospective study. Setting A tertiary care hospital. Methods This study was divided into 2 groups according to gENE status: the gENE group and non-gENE group. We compared the disease persistence/recurrence rates of these 2 groups in the entire cohort and by individual risk group (intermediate/high risk), analyzed whether gENE was an independent risk factor for disease persistence/recurrence, and explored the impact of gENE-specific features on disease persistence/recurrence. Results There were 989 patients who satisfied the inclusion criteria: 57 patients in the gENE group and 932 in the non-gENE group. The disease persistence/recurrence rate of the gENE group was higher than that of the non-gENE group in the entire cohort and by individual risk group ( P < .05 for each). Unexpectedly, the outcomes of the gENE group with intermediate risk were similar to those of the non-gENE group with high risk ( P = .72). For the entire cohort, gENE was an independent predictor for disease persistence/recurrence (odds ratio, 2.89; 95% CI, 1.39-6.00; P = .005). Specific features of gENE ( P > .05 for each) were not related to disease persistence/recurrence. Conclusion Patients with gENE and intermediate risk might be regraded as high risk. Specific features of gENE have no impact on disease persistence/recurrence.

scholarly journals SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4540
Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Workers ◽  
Risk Group ◽  
Close Contact ◽  
Virus Transmission ◽  
High Risk Group ◽  
Low Risk ◽  
University Hospital ◽  
Intermediate Risk ◽  
Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

scholarly journals The Impact of Preoperative Risk on the Association between Hypotension and Mortality after Cardiac Surgery: An Observational Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2057
Author(s):  
Vanja Ristovic ◽  
Sophie de Roock ◽  
Thierry G. Mesana ◽  
Sean van Diepen ◽  
Louise Y. Sun
Keyword(s):  
Cardiac Surgery ◽  
Risk Factor ◽  
High Risk ◽  
Hospital Mortality ◽  
Risk Group ◽  
High Risk Group ◽  
Group Care ◽  
Intermediate Risk ◽  
Intraoperative Hypotension ◽  
The Impact

Background: Despite steady improvements in cardiac surgery-related outcomes, our understanding of the physiologic mechanisms leading to perioperative mortality remains incomplete. Intraoperative hypotension is an important risk factor for mortality after noncardiac surgery but remains relatively unexplored in the context of cardiac surgery. We examined whether the association between intraoperative hypotension and in-hospital mortality varied by patient and procedure characteristics, as defined by the validated Cardiac Anesthesia Risk Evaluation (CARE) mortality risk score. Methods: We conducted a retrospective cohort study of consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass (CPB) from November 2009–March 2015. Those who underwent off-pump, thoracic aorta, transplant and ventricular assist device procedures were excluded. The primary outcome was in-hospital mortality. Hypotension was categorized by mean arterial pressure (MAP) of <55 and between 55–64 mmHg before, during and after CPB. The relationship between hypotension and death was modeled using multivariable logistic regression in the intermediate and high-risk groups. Results: Among 6627 included patients, 131 (2%) died in-hospital. In-hospital mortality in patients with CARE scores of 1, 2, 3, 4 and 5 was 0 (0%), 7 (0.3%), 35 (1.3%), 41 (4.6%) and 48 (13.6%), respectively. In the intermediate-risk group (CARE = 3–4), MAP < 65 mmHg post-CPB was associated with increased odds of death in a dose-dependent fashion (adjusted OR 1.30, 95% CI 1.13–1.49, per 10 min exposure to MAP < 55 mmHg, p = 0.002; adjusted OR 1.18 [1.07–1.30] per 10 min exposure to MAP 55–64 mmHg, p = 0.001). We did not observe an association between hypotension and mortality in the high-risk group (CARE = 5). Conclusions: Post-CPB hypotension is a potentially modifiable risk factor for mortality in intermediate-risk patients. Our findings provide impetus for clinical trials to determine if hemodynamic goal-directed therapies could improve survival in these patients.

809 Phase 2 trial of neoadjuvant and adjuvant PD-1 checkpoint blockade in local-regionally advanced, resectable HNSCC indicates pathological response is associated with high disease-free survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A859-A860
Author(s):  
Trisha Wise-Draper ◽  
Shuchi Gulati ◽  
Vinita Takiar ◽  
Sarah Palackdharry ◽  
Francis Worden ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Free Survival ◽  
Disease Free

BackgroundPatients with newly diagnosed, resected, head and neck squamous cell carcinoma (HNSCC) with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year disease free survival (DFS) of 65% and 69%, respectively.1 PD-1/PD-L1 immune checkpoint blockade has improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiation upregulates PD-L1.2 Therefore, we hypothesized that pre and post-operative administration of the PD-1 inhibitor pembrolizumab would improve 1-year DFS for patients with resectable, loco-regionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093).MethodsEligible patients received pembrolizumab (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembrolizumab (q3 wks x 6 doses) was administered with weekly cisplatin (40mg/m2 X 6) and radiation (60-66Gy) for those with high-risk features and radiation alone for patients with intermediate-risk features. The primary endpoint was DFS, which was compared by log-rank test to historical controls (RTOG 9501). Evidence of pathological response to neoadjuvant pembrolizumab was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE) defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. Response was classified as none (NPR, <20%), partial (PPR, ≥20% and <90%) and major (MPR, ≥90%) pathological response. Gene expression analysis in paired tumor specimens was evaluated by Nanostring.ResultsSixty-six of 84 enrolled patients had received adjuvant pembrolizumab and therefore were evaluable for DFS at the time of interim analysis. Patient characteristics included: median age 59 (range of 27 – 76) years; 30% female; 85% oral cavity, 11% larynx, and 2% human papillomavirus negative oropharynx; 85% clinical T3/4 and 68% ≥2N; 41(51%) high-risk (positive margins, 49%; ECE, 80%). At a median follow-up of 16 months, 1-year DFS was 66% (95%CI 0.48-0.84) in the high-risk group (p=1) and 91% (95%CI 0.79-1) in the intermediate-risk group (versus 69% in RTOG 9501, p=0.05) (figure 1). Among 70 patients evaluable for pathological response, TE was scored as NPR in 40, PPR in 27, and MPR in 3 patients. Patients with pathological response that were also evaluable for DFS (PPR + MPR) had significantly improved 1-year DFS when compared with those with NPR (100% versus 57%, p=0.0033; HR = 0.18 [95%CI 0.05-0.64]) (figure 2). PPR/MPR was associated with robust macrophage infiltration via Nanostring.Abstract 809 Figure 1Disease Free Survival by Pathological RiskPatients were stratified by pathological risk and DFS was measuredAbstract 809 Figure 2Disease Free Survival by Pathological ResponsePaired patient tissue was assessed for treatment effect (TE) and patients with greater than or equal to 20% TE were considered to have developed pathological response. Patients were stratified into responders and non-responders and DFS was determined.ConclusionsNeoadjuvant and adjuvant pembrolizumab led to high DFS in intermediate-risk, but not high-risk, resected HNSCC patients. Pathological response to neoadjuvant pembrolizumab was associated with high 1-year DFS.AcknowledgementsWe’d like to acknowledge the UCCC clinical trials office for their hard work on this study as well as our patients. We’d also like to acknowledge Merck & Co, Inc as they partially funded the clinical trial.Trial RegistrationNCT02641093Ethics ApprovalThis study was approved by the University of Cincinnati IRB with approval number 2015-6798ReferencesCooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350(19):1937-1944. doi:10.1056/NEJMoa032646Oweida A, Lennon S, Calame D, et al. Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. Oncoimmunology2017;6(10):e1356153. Published 2017 Aug 3. doi:10.1080/2162402X.2017.1356153

scholarly journals Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592092821
Author(s):  
Li-Ting Liu ◽  
Yu-Jing Liang ◽  
Shan-Shan Guo ◽  
Hao-Yuan Mo ◽  
Ling Guo ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Risk Group ◽  
Risk Groups ◽  
Rank Test ◽  
Intermediate Risk ◽  
Free Survival ◽  
Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

Efficacy and tolerability of adjuvant therapy in ≥70-year-old patients with T3N0M0 colorectal cancer: An observational study

2019 ◽  
Vol 26 (3) ◽  
pp. 619-631
Author(s):  
Abdullah Sakin ◽  
Nurgul Yasar ◽  
Suleyman Sahin ◽  
Serdar Arici ◽  
Saban Secmeler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Risk Group ◽  
Disease Free Survival ◽  
Old Patients ◽  
Free Survival ◽  
Disease Free

Background This study aimed to retrospectively investigate the efficacy and tolerability of adjuvant chemotherapy in ≥70-year-old patients with stage IIA (T3N0M0) colorectal cancer. Methods Lymphovascular invasion, perineural invasion, margin positivity, dissected lymph node count of <12, and presence of perforation/obstruction were accepted as risk factors. Those patients with at least one risk factor were regarded as having high risk. Results The study included 168 patients, among which 95 (56.5%) were male and 73 (43.5%) were female. The median age of patients was 73 years (range: 70–94). One hundred one (60.1%) patients were identified to have high risk. Eighty-one (87%) patients received 5-flourouracil+leucovorin and 12 (13%) patients received capecitabine regimens as adjuvant chemotherapy. The patients receiving capecitabine regimen had significantly higher rates of dose reduction at initiation and during the treatment. Among low-risk group, there was no statistically significant difference between patients with and without adjuvant chemotherapy in terms of disease-free survival or overall survival (p = 0.528 and p = 0.217, respectively). In high-risk group, patients receiving adjuvant chemotherapy significantly differed from those not receiving adjuvant chemotherapy in terms of median disease-free survival and overall survival (p = 0.009 and p < 0.001, respectively). While the grade, lymph node status, and adjuvant chemotherapy were identified as the most significant independent factors for disease-free survival, the most significant factors for overall survival were the age, Eastern Cooperative Oncology Group performance status, adjuvant chemotherapy, and recurrence. Conclusion The findings of our study showed improved disease-free survival and overall survival in high-risk ≥70-year-old patients who received adjuvant chemotherapy due to T3N0M0 colorectal cancer. We believe that 5-flourouracil+leucovorin or capecitabine regimens should be recommended for these older high-risk patients who could receive adjuvant chemotherapy regardless of age.

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