Prognostic value of BRAFV600 mutations in melanoma patients after resection of metastatic lymph nodes.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8540-8540
Author(s):  
Philippe Saiag ◽  
Stephanie Moreau ◽  
Philippe Aegerter ◽  
Daphne Bosset ◽  
Christine Longvert ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Primary Melanoma ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Rank Test ◽  
Braf Mutations

8540 Background: Prognosis of AJCC stage III melanoma is heterogeneous. BRAFV600 mutations are frequent in melanomas. BRAFV600-targeted therapy has dramatic, but often transitory, efficacy in stage IV patients (pts). We aimed to determine for the first time the prognostic value of BRAFV600 mutations and other known prognostic criteria in stage III pts with sufficient nodal invasion. Methods: We searched all pts with cutaneous melanoma who had radical lymphadenectomy in our institution between 1/1/00 and 15/6/10 and included those with a nodal deposit >2 mm. BRAFV600 mutations were detected by DNA sequencing and pyrosequencing in formalin-fixed nodal samples containing >60% melanoma cells. Samples were considered mutated when >15% of DNA was positive. Endpoints were overall survival (OS) and distant metastasis free survival (DMFS). 92 patients had to be included to demonstrate a doubling of OS in patients without (40 months (m)) and with BRAFV600 mutation (20 m). Log-rank test and multivariate Cox proportional hazards regression model were used. Results: 105 consecutive pts were included, with 72% prospectively followed-up pts. BRAFV600 mutations (E: 83%; K: 14% of pts) were detected in 40% of pts. Median follow-up was 19 m (range: 3-139). Death occurred in 83% and 60% of pts with and without BRAF mutations, respectively, with median OS of 1.4 and 2.8 years. Pts’ age, primary melanoma ulceration, number of invaded nodes, AJCC staging, and BRAF status influenced OS and DMFS in the univariate analysis. The multivariate analysis showed the major prognostic role of BRAF status and of the number of invaded nodes (table). Conclusions: Provided our findings are independently replicated, BRAFV600 status should be used to stage melanoma pts with nodal metastasis. Our results also help to plan adjuvant trials with BRAFV600-targeted therapy in such patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies. [Table: see text]

Prognostic factors for survival in patients with stage (stg) IV malignant melanoma (MM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9072-9072
Author(s):  
N. Seetharamu ◽  
H. Hamilton ◽  
T. Tu ◽  
P. Christos ◽  
I. Osman ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Univariate Analysis ◽  
Primary Melanoma ◽  
Stage Iv ◽  
Female Gender ◽  
Cox Proportional Hazards ◽  
Independent Effect ◽  
P Value ◽  
Related Factors ◽  
Ajcc Staging

9072 Background: Prognosis for survival in MM is not uniform with some pts being long-term survivors. Identifying this subset of pts may have implications on surveillance and treatment (tx). Unfortunately, prognostic data available for MM and the utility of AJCC staging in predicting survival is limited. We analyzed prospectively collected data from the NYUCI Interdisciplinary Melanoma Cooperative Group program (IMCG) to identify clinicopathological variables predictive of MM survival. Methods: We identified 185 pts enrolled in the IMCG with MM diagnosed and treated at NYUCI. Demographic, clinical, and tx-related factors were included in the analysis. Kaplan-Meier (KM) survival analysis was used to identify univariate predictors of post-stage IV survival and their independent effect was assessed in a multivariate Cox proportional hazards regression model. Results: Median age at diagnosis (dx) of metastatic MM was 64 years (22–92). Median overall survival: 13.8 months(m) (128 deaths and a median follow up of 18.6 m (4–141) for survivors). Factors identified on univariate analysis at p<0.20 were evaluated in the multivariate model ( table ). Co-morbidities, site and histology of primary melanoma, initial staging, prior loco-regional recurrences, and adjuvant tx of primary melanoma were not associated with MM survival. Univariate analysis also showed significant survival advantage (p value 0.0011) for patients with AJCC stages M1a and M1b (21.6 m and 17.2 m respectively) over those with AJCC stage M1c (9 m). Conclusions: This cohort study of MM identified female gender, nl serum LDH, nl albumin, and solitary organ involvement as independent survival predictors. Patients who received systemic therapy± local measures had survival benefit over those that had surgery and/or radiation alone suggesting a role for systemic treatment in MM. Patients with personal history of another malignancy (n=37) showed a trend towards improved survival. This novel observation needs to be validated and studied further. [Table: see text] No significant financial relationships to disclose.

scholarly journals Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rachel Howard ◽  
Peter A. Kanetsky ◽  
Kathleen M. Egan
Keyword(s):  
Prognostic Value ◽  
Clinical Characteristics ◽  
Proportional Hazards ◽  
Area Under The Curve ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Neutrophil To Lymphocyte Ratio ◽  
Cancer Center ◽  
Lymphocyte Ratio ◽  
Patient Subgroups

AbstractIn cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple “high-risk” demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.

Validation of CA-125 concentration nadir within the normal range following primary treatment as a predictor of survival for epithelial ovarian cancer (EOC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16007-16007
Author(s):  
A. Prat ◽  
J. Del Campo ◽  
S. Peralta ◽  
S. Cedres ◽  
A. Perez ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Model ◽  
Primary Treatment ◽  
Cox Proportional Hazards ◽  
University Hospital ◽  
Stage Iii ◽  
Ca 125 ◽  
Rank Test ◽  
Normal Range

16007 Background: Recent studies suggest that the CA-125 nadir within the normal range after surgery and chemotherapy treatment is a predictor of survival (Crawford, ASCO 2004; Crawford, Ann Oncol 2005) and relapse (Markman, J Clin Oncol 2006). In order to validate these previous findings, we have conducted a retrospective analysis of patients (pts) treated in our institution for EOC. Methods: Between March 1, 1997, and October 30, 2005, all pts treated for EOC at Vall d'Hebron University Hospital were identified from the tumor registry database and screened retrospectively for their standard prognostic factors (age at diagnosis (=65 vs. >65), stage (III-IV vs. IC-II), and suboptimal vs. optimal cytorreduction). Inclusion criteria: an elevated CA-125 at time of diagnosis (>35 U/mL); primary treatment (PT) that consisted in surgery and intravenous carboplatin/paclitaxel for a maximum of 6–9 cycles; complete clinical and radiological response to initial treatment with normalization of CA-125 (=35 U/mL); and disease status at the time of last follow-up. Standard Kaplan-Meier methods were used to plot the progression-free survival (PFS) of members of each of the nadir groups. The relative contribution of the different potential correlates of prognosis was assessed by the Cox proportional hazards method. Results: 123 pts were identified: 64 Group A (=10 U/mL), 42 Group B (11–20 U/mL), 17 Group C (21–35 U/mL). Median age: 56. Stage IC 25%, II 13%, III 52%, IV 10%. Median follow-up 39.2 months (m). Median PFS was 69.7 m, 27.7 m, and 15.8 m for A, B and C, respectively (p< .0001, log-rank test). The Cox model showed a highly-significant impact on PFS in relation to CA-125 nadir levels, residual tumor after surgery and stage. Hazard ratios (HR) for PFS (95% CI) of B vs. A, C vs. B, and C vs. A were 1.98 (p= .034), 2.35 (p= .02), and 4.67 (p< .001), respectively. HR for PFS (95% CI) of suboptimal vs. optimal cytorreduction and stage III-IV vs. IC-II were 1.84 (p= .058) and 3.2 (p= .002), respectively. Conclusions: The CA-125 nadir in the normal range following PT for EOC is a reproducible predictor of PFS in stage IC-IV. Prospective studies of maintenance-consolidation therapies or different approaches in selected pts based on CA-125 nadir seem warranted. No significant financial relationships to disclose.

scholarly journals Association of antibiotic exposure with survival and toxicity in patients with melanoma receiving immunotherapy

2020 ◽  
Author(s):  
Jahan J Mohiuddin ◽  
Brian Chu ◽  
Andrea Facciabene ◽  
Kendra Poirier ◽  
Xingmei Wang ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Statistical Tests ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Antibiotic Exposure ◽  
Immune Mediated ◽  
Stage Iv Disease ◽  
Antibiotic Group

Abstract BACKGROUND Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. METHODS Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was pre-specified. The primary outcome was overall survival (OS) and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous (IV) steroids. All statistical tests were two-sided. RESULTS There were 568 patients in our database, of which 114 received antibiotics prior to ICI. 35.9% of patients had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.27-2.57, p&lt;.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR 2.78, 95% CI 1.31-5.87, p=.007). When limited to only patients who received adjuvant ICI (N = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR 4.84, 95% CI 1.09-21.50, p=.04). The antibiotic group had a greater incidence of colitis (HR 2.14, 95% CI 1.02-4.52, p=.046). CONCLUSION Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.

Trends in treatment and survival for advanced pancreatic cancer: Progress or progression?

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 421-421
Author(s):  
Mariam F. Eskander ◽  
Gyulnara G. Kasumova ◽  
Chun Li ◽  
Sing Chau Ng ◽  
Rebecca A. Miksad ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Tumor Location ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Cox Proportional Hazards Models

421 Background: There are increasing therapeutic options for patients with advanced pancreatic cancer but it is unknown whether the overall prognosis of unresectable patients is improving. Here, we examine trends in treatment and survival in Stage III/IV pancreatic cancer. Methods: National Cancer DataBase 1998-2012 queried for unresected pancreatic adenocarcinoma patients from Commission on Cancer hospitals with Stage III and IV disease. Trends in stage at diagnosis and type of chemotherapy (single vs. multi-agent) assessed via Cochran Armitage trend tests. Timing of treatment compared by Kruskal-Wallis. Kaplan-Meier analysis and Cox proportional hazards models used to assess the association between 2-year time intervals (1998-2011) and survival. Results: 34,163 unresected patients with Stage III and 100,396 with stage IV identified. Rates of chemotherapy increased over time for stage III (p<0.0001) and stage IV (p<0.0001). Among patients who received systemic therapy, rates of multiagent chemotherapy have increased for both stage III (p<0.0001) and IV (p<0.0001). Time from diagnosis to treatment did not change (p=0.5121). Overall survival differed by year group for stage III (5.2 mos in 1998-1999 vs. 9.0 mos 2010-2011, log-rank p<0.0001) and stage IV (3.1 vs. 3.6 mos; log-rank p<0.0001). Among patients who received chemotherapy, overall survival also differed (Stage III, 7.6 vs. 11.4 mos, log-rank p<0.0001; Stage IV, 5.0 vs. 6.0 mos, log-rank p<0.0001). After stratification by clinical stage, type of chemotherapy, tumor location, and facility type, year remained a significant predictor of survival (p<0.0001). Conclusions: Survival of patients with Stage III and IV pancreatic cancer has significantly improved over the last fifteen years. This improvement in survival is not fully explained by changes in chemotherapy. [Table: see text]

Comprehensive genomic and transcriptomic profiling (CGTP) to predict pembrolizumab (P) benefit in patients (pts) with advanced solid tumors (STs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2609-2609
Author(s):  
Dan Rhodes ◽  
Daniel H Hovelson ◽  
Malek M. Safa ◽  
Mark E. Burkard ◽  
Eddy Shih-Hsin Yang ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Predictive Biomarkers ◽  
Initial Therapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Observational Trial ◽  
Highly Correlated

2609 Background: P is approved in many ST types, however predictive biomarkers and the proportion of pts who benefit vary widely. Biomarkers beyond PD-L1 immunohistochemistry and comprehensive genomic profiling (CGP) based tumor mutation burden (TMB) may improve benefit prediction. We determined if treatment data and CGTP collected in an ongoing observational trial (NCT03061305) could predict pan-ST P benefit. Methods: Eligible advanced ST pts had QC-passing TMB and expression data from multiplex PCR based tissue CGTP on FFPE tissue (StrataNGS and an investigational test) and documented P treatment > 1 month. Real-world time to next treatment (TTNT) was defined as time in months from therapy start to new therapy start (after stopping initial therapy) or death. TMB and gene expression biomarker association with P TTNT was evaluated. Backward stepwise regression was performed to fit a multivariate Cox proportional hazards model; pts were assigned to four score groups (IRS 1-4) based on overlapping TTNT curves from 8 equal bins. P TTNT were compared between IRS groups by log-rank test. A chemotherapy (C) comparator cohort was established from C TTNT for pts in this cohort. Results were stratified by ST type, P mono vs. C combo, and TMB status. Results: 610 pts (254 [41.6%] NSCLC; 356 [58.4%] from 23 other ST types) with CGTP and P treatment were identified; P TTNT was highly correlated to overall survival (n=146; Pearsons r2=0.75). By univariate analysis of TMB and 9 expression biomarkers, TMB, two independent PD-L1 expression amplicons, and PD-L2 expression were significantly associated with P TTNT (all p ≤ 0.002). The most significant multivariate model included 5 variables, with 1) increasing TMB, PD-L1, and PD-L2, and 2) decreasing TOP2A (proliferation) and GZMA as P TTNT predictors. Median P TTNT, but not C TTNT (345 courses from 254 pts), differed significantly by IRS group (Table). Median P TTNT by IRS group did not significantly differ by non-small cell lung vs. other ST type or P mono vs. C combo (both p > 0.05); excluding TMB-high patients, median P TTNT was still significantly longer in IRS groups 3/4 vs. 1/2 (p = 5.0e-4). Across 19,623 total evaluable pts in NCT03061305, 12.2% were in IRS groups 3/4 and outside of P approved ST types/TMB-low. Conclusions: CGTP in an observational trial cohort demonstrated that TMB, PD-L1 and PD-L2 independently predicted pan-ST P benefit as assessed by OS-validated TTNT. A multivariate CGTP signature predicted P benefit relative to C across ST types. If further validated, such a signature may enable improved P benefit prediction. P versus C TTNT by IRS group. Clinical trial information: NCT03061305. [Table: see text]

Prognostic Value of the Albumin-to-Alkaline Phosphatase Ratio before Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Liping Yang ◽  
Jing Gao ◽  
Yan Zhou ◽  
Zhenchao Tao ◽  
Jian He ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Nasopharyngeal Carcinoma ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Optimal Cutoff ◽  
Free Survival

Introduction: The aim of this study was to evaluate the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) in patients with nonmetastatic nasopharyngeal carcinoma (NPC). Methods: Patients with nonmetastatic NPC who underwent chemoradiotherapy (CRT) were retrospectively analyzed. The AAPR was calculated using the last value of albumin to alkaline phosphatase that was measured within 1 week before CRT. The optimal cutoff value for the AAPR value was determined by an X-tile plot. Propensity score matching (PSM) was performed to balance the differences of the baseline characteristics. The Kaplan-Meier method and log-rank test were used to calculate the survival. A Cox proportional hazards regression model was conducted for the multivariate analysis. Results: Totally, 87 patients with nonmetastatic NPC who underwent CRT were included in the analysis. The optimal cutoff level for the AAPR was 0.46. The group with an AAPR ≤0.46 was more likely to have poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (p = 0.023, p = 0.031 and p = 0.027, for OS, PFS, and DMFS, respectively). In Cox proportional hazards analysis, high AAPR was a better prognostic predictor. Conclusion: AAPR may be a reliable prognostic index for nonmetastatic NPC patients.

Expression Of CD25 Antigen On CD34+ Cells Is An Independent Predictor Of Survival In Late Stage MDS Patients Treated With Azacitidine

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1508-1508
Author(s):  
Ioannis Kotsianidis ◽  
Paraskevi Miltiades ◽  
Eleftheria Lamprianidou ◽  
Theodoros Vassilakopoulos ◽  
Sotirios G Papageorgiou ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
De Novo ◽  
Univariate Analysis ◽  
Rank Test ◽  
Color Flow ◽  
Cd25 Expression ◽  
Transfusion Requirements ◽  
Blast Count

Abstract Expression of CD25 on blasts of AML patients has been shown to hold independent prognostic value for both survival and response to induction therapy. Patients with MDS-related AML have generally higher CD25 expression from de novo AML patients, but though there is paucity of a serviceable biomarker of outcome in MDS patients treated with azacytidine, the prognostic value of CD25 has not yet been investigated. Bone marrow samples of 61 patients with intermediate-2/high risk IPSS, high/very high WPSS and low blast count AML were obtained before and 15 days (D15) after the initiation of treatment. All patients received azacytidine in a non clinical trial setting at an initial dose of 75mg/m2 SC for 7 days on 28-day cycles. CD25 expression was assessed by 4-color flow cytometry on total CD34+ blasts, committed progenitors (Lin-CD38+CD34+) and leukemic stem cells (LSC, Lin-CD38-CD34+). Positivity was defined as a CD25 expression of ≥ 20%. Statistical comparisons were done by ÷2, one-way ANOVA and paired or unpaired t-test as appropriate, and survival with Kaplan-Meier analysis and log-rank test. Overall survival (OS) was defined as the time from azacytidine initiation to death from any cause and event-free survival (EFS) as the time from diagnosis to disease progression, relapse or death. Multivariate survival analysis was based on Cox’s proportional hazards model using a backward stepwise selection procedure with entry and removal criteria of p=0.05 and p=0.10, respectively. As shown in table 1 the cohorts of CD25- and CD25+ patients were well balanced for most known predictive factors and characteristics, except sex. Compared to CD25+ patients the CD25- ones have significantly longer OS (16.2 vs 8.8 months, respectively, p=0.04) and EFS (12.8 vs 6.66 months, p=0.04) in univariate analysis. Multivariate analysis confirmed the independent predictive power of CD25 for OS and EFS (p=0.006 and p=0.009, respectively), whereas heavy transfusion requirements (p=0.003 and p=0.002) and age>75 (p=0.02 and p=0.02) were also independent predictors. The average expression of CD25 in CD34+ blasts of all patients was 21.6%±24%. Compared to committed progenitors, LSCs displayed higher expression (19.4%±23.7% vs 24.1%±28.2%, respectively, p=0.027). Interestingly, on D15 CD25 was downregulated in LSCs (p=0.03) but remained stable in committed progenitors (p=0.8, n=18), indicating a particular sensitivity of the CD25+ subset of LSCs in azacytidine.Table 1Patient characteristics. N/A: not applicable/not available.CD25- (n=36)CD25+ (n=25)p-valueAge72,5 (53,4-83.5)72,9 (52-81.7)0.2 >6531(86%)17(68%) <655(14%)8(32%)Sex0.027 Male20(55%)21(84%) Female16(45%)4(16%)WHO classification0.28 RCMD2(5%)0(0%) RAEB-I0(0%)1(4%) RAEB-II17(47%)13(52%) CMML-II6(16%)7(28%) Low blast count - sAML11(30%)4(16%)Baseline blood counts Hemoglobin (g/dl)8,6(6.1-10.6)8,8(6.8-11.5)0.78 ANC(x 109/L)1,1(0.04-13.4)2,8(0.08-23)0.07 Platelets (x 109/L)66(9-383)50(11-181)0.42IPSS0.6 Intermediate-217(47%)9(36%) High8 (22%)6(24%) N/A11(31%)10(40%)WPSS0.22 High15(42%)8(32%) Very high6(16%)7(28%) N/A15(42%)10(40%)IPSS-R0.8 Intermediate3(8%)1(4%) High14(39%)8(32%) Very high17(48%)12(48%) N/A2(5%)6(24%)IPSS-R Cytogenetic risk0.72 Good18(50%)10(40%) Intermediate8(22%)6(24%) Poor5(14%)6(24%) Very poor4(11%)2(8%) N/A1(3%)1(4%)PB blasts0.5 Present19(53%)13(52%) Absent14(39%)11(44%) N/A3(8%)1(4%)BM blasts0.2 >15%18(50%)9(36%) ≤15%18(50%)16(54%)Transfusions ≥ 4 per month0.48 Yes23(4%)17(4%) No13(4%)8(4%)Response0.4 CR & PR12(33%)4(16%) Hematologic improvement5(14%)4(16%) Stable disease8(22%)5(20%) Failure11(31%)12(48%)Figure 1(A) OS and EFS according to CD25 positivity status. (B) OS and EFS according to transfusion requirements.Figure 1. (A) OS and EFS according to CD25 positivity status. (B) OS and EFS according to transfusion requirements. Collectively, our findings reveal an independent prognostic role for CD25 in MDS patients treated with azacytidine. In addition, the differential expression and epigenetic modulation of CD25 in the LSC compartment support the investigation of therapeutic strategies using monoclonal antibody targeting combined with epigenetic agents. Disclosures: Kotsianidis: Genesis Hellas: Honoraria, Research Funding. Spanoudakis:Genesis Hellas: Honoraria. Tsatalas:Genesis Hellas: Honoraria.

Clinical behavior of stage IVC squamous cell carcinoma of the head and neck.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17511-e17511
Author(s):  
Vanessa Wookey ◽  
Adams Kusi Appiah ◽  
Avyakta Kallam ◽  
Vinicius Ernani ◽  
Lynette Smith ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Proportional Hazards ◽  
Private Insurance ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test

e17511 Background: Squamous cell carcinoma of the head and neck (HNSCC) with distant metastasis at diagnosis (stage IVC) is rare, and outcomes are often lumped together with those of patients who relapse following initial treatment. We evaluated prognostic factors in patients presenting with stage IVC HNSCC. Methods: Data was extracted from the National Cancer Database to determine prevalence, overall survival (OS), and prognostic factors of stage IVC HNSCC (oral cavity, gum, lip, oropharynx, tongue, tonsil and hypopharynx) in adults, using SAS software for analysis. OS curves were estimated using the Kaplan-Meier method and differences were compared using a log-rank test. Significant parameters in the univariate Cox proportional hazards regression model analyses were included in the multivariate model, and hazard ratios, p-values and 95% confidence intervals were presented. Results: Of 226,302 patients with HNSCC, 5458 had distant metastases at diagnosis (2.40%); 5238 had complete data and were included in further analyses. Median survival of the entire cohort was 9.07 months, and one-year survival was 41%. Age > 70 years, Black race and higher Charlson-Deyo comorbidity score were associated with worse OS, while HPV positive status, tonsil and tongue (not including base) primary, private insurance and receipt of any treatment were associated with improved OS on univariate analysis. In multivariate analysis, HPV positive tumors were associated with improved OS compared to HPV negative tumors (HR 0.63, 95% CI 0.48-0.82; p= 0.001), even after adjusting for site of tumor origin. Only patients with a Charlson-Deyo score of ≥2 had worse OS compared to those without comorbidities. Hypopharynx, lip, tonsil and base of tongue primaries had significantly worse OS compared to gum and other mouth. Except for radiation alone and radiation with surgery, treatment demonstrated significant improvement in OS compared to no treatment, a combination of chemotherapy, radiation and surgery provided the largest survival benefit (HR 0.23, 95% CI 0.20-0.28). Conclusions: HPV positivity seems to predict for better prognosis, regardless of site of origin. Patients with metastatic HNSCC should be offered multimodality therapy in order to improve outcomes.

scholarly journals Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm

2016 ◽  
Vol 124 (1) ◽  
pp. 163-174 ◽  
Author(s):  
Zachary A. Seymour ◽  
Penny K. Sneed ◽  
Nalin Gupta ◽  
Michael T. Lawton ◽  
Annette M. Molinaro ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Radiation Dose ◽  
Arteriovenous Malformations ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Log Rank Test ◽  
Complete Obliteration ◽  
Treatment Volume

OBJECT Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004–2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages. METHODS All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed. RESULTS Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9–68 years). The median modified radiosurgery-based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose ≥ 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97–16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant). CONCLUSIONS VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to ≤ 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure.

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