Palbociclib exposure-response analyses in second-line treatment of hormone-receptor positive advanced breast cancer (ABC).

1053 Background: Palbociclib (PAL) is an oral inhibitor of cyclin-dependent kinases 4 and 6 approved for ABC. Exposure-response analyses for efficacy and safety endpoints were performed to evaluate the current PAL clinical dosing regimen (125 mg daily, 3 weeks on and 1 week off) and dose modification strategy in 2nd-line ABC. Methods: The present analyses used data from PALOMA3, a phase 3 study comparing the safety and efficacy of fulvestrant plus either PAL or placebo in 2nd-line ABC patients (PTs). A Bayesian pharmacokinetic (PK) analysis was conducted to estimate PAL PK parameters for individual PTs. Average concentration of PAL over the entire treatment (Cavg) was derived from average daily dose intensity divided by post hoc estimates of clearance for each PT. Time varying Cavg (Cavgt) was also derived to account for dose modifications up to each observation point. Kaplan-Meier method and the Cox proportional hazards model were employed to explore relationship between progression-free survival (PFS) and Cavg, Cavgt, as well as other prognostic factors. A semi-mechanistic PK-pharmacodynamic (PD) model was built to quantify the relationship between PAL concentration and absolute neutrophil count (ANC). Results: The median PFS for low and high PAL exposure groups divided according to Cavg were similar (9.47 and 10.9 months, respectively) and significantly higher than that of the control arm (4.57 months). While Cavgtwas found to be a significant predictor for PFS in univariate analysis (P-value < 0.05), this relationship was not significant in the multivariate analysis where other significant prognostic factors were also included. The PK-PD analysis for safety endpoint indicated higher PAL concentrations were associated with lower ANC, which is consistent with the fact that ANC profiles were well managed by dose modification strategies, i.e., dose interruption, delay and reduction. Conclusions: The analysis results suggested PTs were benefited similarly from fulvestrant plus PAL treatment with manageable safety profile, supporting a favorable benefit-risk profile of PAL under the current dosing regimen and dose modification strategy in 2nd-line ABC. Funding: Pfizer Inc. Clinical trial information: NCT01942135.

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Hepatocellular carcinoma presenting with lung metastasis: Clinical characteristics and prognostic factors

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15604 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15604-e15604

Author(s):

Y. Kojima ◽

H. Ueno ◽

T. Okusaka ◽

C. Morizane ◽

S. Kondo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Survival Time ◽

Lung Metastasis ◽

Proportional Hazards Model ◽

Lung Metastases ◽

Univariate Analysis ◽

Previous History ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model

e15604 Background: The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) has been limited, but sorafenib has changed the strategy treating for metastatic HCC. The lung is one of the most common metastatic sites for HCC. Therefore, we focused on clinical features and prognostic factors of HCC patients (pts) with lung metastasis in this study. Methods: Between January 2000 and April 2008, 1,117 HCC pts were admitted into our division. During this period, extrahepatic metastasis was detected in 286 pts, and the initial metastatic site was lung in 130 pts. The relationships between the characteristics of these pts at the time of lung metastasis detection and prognosis were examined. Results: There were 107 males and 23 females. Median age was 64 years. The Child-Pugh classification was A in 84 pts, B in 32 pts. HCV Ab was positive in 57 pts, HBs Ag was positive in 46 pts, and both were negative in 27 pts. The median survival time of all pts was 298 days. Univariate analysis revealed 12 of the 20 variables evaluated to be significantly associated with survival time: number of lung metastasis, presence of intrahepatic HCC, maximum size of intrahepatic HCC, presence of tumor thrombus, AFP, PIVKA II, albumin, prothrombin time, ALP, presence of ascites, Child-Pugh classification, and previous history of hepatic resection. Multivariate analysis using the Cox proportional hazards model demonstrated a lower number (≤5) of lung metastases (p<0.0001), the absence of intrahepatic HCC (p=0.0002), and the absence of ascites (p=0.0339) to be independent favorable prognostic factors. Conclusions: These results may provide useful reference data for determining treatment strategies and planning further clinical trials involving HCC patients with lung metastasis. No significant financial relationships to disclose.

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Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer

Cancers ◽

10.3390/cancers13225629 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5629

Author(s):

Yusuke Sugino ◽

Takeshi Sasaki ◽

Manabu Kato ◽

Satoru Masui ◽

Kouhei Nishikawa ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Univariate Analysis ◽

Psoas Muscle ◽

Hounsfield Unit ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cross Sectional

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

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Randomized Open-Labeled Academic Trial Comparing Standard AZA Therapy with Combination of G-CSF with AZA in High Risk MDS Patients - Interim Analysis

Blood ◽

10.1182/blood-2019-124274 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1729-1729

Author(s):

Anna Jonasova ◽

Lubomir Minarik ◽

Vojtech Kulvait ◽

Michal Pesta ◽

Adel Schaffartzikova ◽

...

Keyword(s):

Flow Cytometry ◽

Mixed Model ◽

Proportional Hazards Model ◽

Patient Survival ◽

Conflicts Of Interest ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

P Value ◽

Pre Treatment ◽

Time Varying Covariates

Introduction: Myelodysplastic syndrome (MDS) is characterized by differentiation blockade, cytopenias with commontransfusion dependency and immune defects. Upon progression the myeloblasts accumulate and the patients become vulnerable to severe infection complications. Based on the Prague Charles University General Hospital registry (N=164, median age 73), the AZA therapy in higher-risk MDS patients results in median OS 13.8 Mo with ORR 48.5%. We also noted from our retrospective data that AZA-treated patients with higher G-CSF consumption had significantly reduced occurrence of Grade 4 neutropenias and longer OS (19 vs 16 Mo, p value 0.039). Rationale: To improve poor clinical outcomes we initiated a randomized open labeled academic trial that compares standard AZA therapy (A) with novel AZA-based therapy combination involving use of G-CSF added prior AZA (GA). Both AZA and also decitabine were preclinically shown to induce myeloid differentiation upon G-CSF preincubation. G-CSF binds its receptor in granulocytic precursors and neutrophils to stimulate their survival, proliferation, and differentiation via myeloid master regulator transcription factor and leukemia-suppressor PU.1. We also have previously shown that AZA increases PU.1. expression. Study design & Methods: GA/MDS-2013 (EudraCT No 2013-001639-38). Expected for enrollment are 134 patients, currently enrolled 53 patients (GA arm N=29, A arm N=24) with median age 74 years, M:F ratio 32:21 (GA 16:16, A 13:8),median IPSS-R 6, median follow up 11.2 Mo, median cycles of therapy 6. Diagnosis included:MDS (EB1, EB 2) with IPSS int-2/high (75%), MDS/AML<30% MB (22.5%), and CMML II (2.5%). Transplant candidates were excluded. Randomization is 2:1 for GA vs A arm. Primary endpoints: OS, PFS, time to AML transformation, ORR, infections & QoL. Secondary endpoints: biomarkers. Therapy schedule: 75mg/m2 of AZA 5-2-2, in GA: G-CSF s.c. injected 48 hrs before dose 1 and dose 6. G-CSF is measured in patient sera (prior therapy), myeloid surface markers are determined by flow cytometry (day -2, day 1, and day 9 of cycle 1). Genomic libraries from whole bone marrow are prepared by NEBNext Direct Kit involving 33 gene panel, sequencing runs are performed on Illumina platform. Statistics involved longitudinal multivariate data analysis including the joint models for the OS and response. Results: The presented data include 2.5 years since the beginning of the trial. Median survival for GA arm was 11 vs 6 Mo in the A arm. ORR (CR, CRm, PR, HI) was 56% in GA arm vs 33% in the A arm. Transformation to AML for both arms was comparable. The stratified longitudinal Cox proportional hazards model containing time-varying covariates together with the ordinal multilevel logistic mixed model were utilized. From this joint fitted model, a negative coefficient for the G-AZA treatment (significant p-value 0.0442) can be noticed in the case of the Cox Proportional Hazard part of the model. This means that G-AZA treatment improves patient survival. The estimated odds for the GA arm that responded to the therapy with remission rather than progression is 12.4x higher than for the A arm, controlling for the remaining patients' characteristics (p-value 0.0016).Both the GA and A arms are comparably tolerated. Data on serious infections and neutropenia gr4 were not yet available. The levels of G-CSF in sera prior the study in both arms (GA vs A) were comparable. Flow cytometry revealed G-CSF mediated upregulation of FCgRI (CD64) in the GA but not in the A arm. Multivariate analysis indicates the following: mutated genes: DNMT3A (p-value 0.0157), EZH2 (p-value 0.0091), TP53 (borderline p-value 0.0510), & CSF3R (p-value 0.0057) shorten the overall survival. The significant negative effects on response was noted for mutated EZH2 (p-value 0.0208) and CSF3R (p-value 0.0424) genes. Conclusions: The current results supported by different methods and statistics indicates a beneficial effect of G-CSF pre-treatment to standard AZA therapy in higher risk MDS patients. G-CSF pre-treatment to AZA increases OS and ORR. In addition, we identified biomarkers that are negatively associated with patient survival and response including EZH2, DNMT3A, TP53, & CSF3R. Grant Support: Ministry of Health, #16-27790A. Institutional resources: Progres Q49 & Q26, UNCE/MED/016, LQ1604, SVV 260374/2017, RVO-64165. Disclosures No relevant conflicts of interest to declare.

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A novel nomogram to predict the overall survival in esthesinoeroblastoma

10.21203/rs.3.rs-22163/v2 ◽

2020 ◽

Author(s):

Lijie Jiang ◽

Tengjiao Lin ◽

Yu Zhang ◽

Wenxiang Gao ◽

Jie Deng ◽

...

Keyword(s):

Overall Survival ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Validation Cohort ◽

Risk Groups ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer Center ◽

P Value ◽

Training Cohort

Abstract Background Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p- value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.

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The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma

Urologia Internationalis ◽

10.1159/000511650 ◽

2020 ◽

pp. 1-7

Author(s):

Volkan İzol ◽

Mutlu Deger ◽

Ender Ozden ◽

Deniz Bolat ◽

Burak Argun ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Univariate Analysis ◽

Upper Urinary Tract ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Recurrence Time ◽

Tumor Biopsy ◽

Group 2 ◽

Group 1

Objective: The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). Materials and Methods: Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. Results: After exclusion, a total of 194 patients were analyzed: Group 1 n = 95 (49.0%) and Group 2 n = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12–250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3–144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (p = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (p =0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (p< 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65–5.41; p < 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74–7.16; p < 0.001) was found to be an independent prognostic factor for IRFS. Conclusion: Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.

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Impact of hemoglobin level on the outcome of advanced non-small-cell lung cancer (NSCLC) treated with cisplatin and gemcitabine

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17010 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17010-17010

Author(s):

O. Juan Vidal ◽

V. Alberola ◽

J. Muñoz ◽

R. De Las Peñas ◽

C. Camps ◽

...

Keyword(s):

Lung Cancer ◽

Advanced Nsclc ◽

Proportional Hazards Model ◽

Negative Impact ◽

Univariate Analysis ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Stage Iiib ◽

Phase Iii ◽

Number Of Cycles

17010 Background: Negative impact of anemia on survival has been described in NSCLC patients (pts) treated with radiotherapy (RT) or concurrent radiochemotherapy, but scarcely data exist in NSCLC treated with chemotherapy (CT). PURPOUSE: To evaluate the prognosis value of baseline hemoglobin (Hb) among pts with advanced NSCLC treated with cisplatin and gemcitabine. Methods: 433 pts included in two trials conducted by the Spanish Lung Cancer Group (176 pts from the arm A of a randomized phase III trial comparing 3 regimens of CT and 257 pts from a phase II trial) were included in this analysis. No significant differences in baseline characteristics, response and survival (median 8.73 and 9.87 months, p=0.46) were observed between pts of the two trials. The baseline Hb and other potential risk factors for survival were analyzed with Cox Proportional Hazards model in an univariate an multivariate analysis. Results: Stage IIIB with positive pleural effusion (25%), stage IV (75%). 85% had ECOG PS 0–1. Median age: 60 years (range 31–82). 89% male. Histology: 41% adenocarcinoma, 39% squamous cell, 6.5% large cell, 14.5% NSCLC not otherwise specified. Median number of cycles received was 4 (range 1–8). Mean Hb level prior CT was 13.2 g/dl (range 8 to 19.6 g/dl). Response rate was 41% and median survival was 9.57 months (95% CI: 8.57–11–57). No statistically differences in survival were observed by stage (IIIB vs IV), age and gender. In the univariate analysis, number of cycles received (≤3 vs. >3 cycles), ECOG (2 vs 0–1), response (SD+PD vs CR+PR), baseline Hb (≤11 vs >11 gr/dl); minimum Hb during the CT (<10 vs ≥10) and second line CT (No vs Yes) emerged as prognostic factors for survival and were introduced in the multivariate model (see Table ). Conclusions: Hb level at the initiation of CT is an independent prognostic factor of survival this homogenous group of advanced NSCLC treated with cisplatin and gemcitabine. Baseline Hb should be considered as prognosis factor for survival in addition to ECOG. [Table: see text] No significant financial relationships to disclose.

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Frequency of use and outcome of surgical resection in the management of malignant mesothelioma in a community-based population: Results in 5,937 patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7510 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7510-7510

Author(s):

R. M. Flores ◽

E. Riedel ◽

J. S. Donington ◽

L. Krug ◽

K. Rosenzweig ◽

...

Keyword(s):

Surgical Resection ◽

Median Survival ◽

Malignant Pleural Mesothelioma ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Univariate Analysis ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Pleural Mesothelioma ◽

Tertiary Referral

7510 Background: Multimodality therapy of mesothelioma patients treated at specialized tertiary hospitals report surgical resection rates of 42% (Flores RM et al. Prognostic Factors in the Treatment of Malignant Pleural Mesothelioma at a Large Tertiary Referral Center. J Thorac Oncol 2007;2(10):957–965.). Treatment strategies in the community are less well defined and surgical expertise is not readily available. We undertook this study to evaluate the rate of surgical resection and its association with survival in a non-tertiary based population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched from 1990 - 2004. Variables analyzed included age, sex, race, year of diagnosis, laterality, vital status, stage, surgery, and reasons for no surgery. The association of resection on overall survival was estimated by the Kaplan-Meier method and examined in a Cox proportional hazards model adjusting for covariates. Results: Pathologically proven malignant pleural mesothelioma was identified in 5,937 patients: 1,166 women, 4,771 men; median age was 70 years. Surgical resection rate was 11% (n=636). Univariate analysis demonstrated a median survival of 13 months with surgical resection and a median survival of 7 months in the non-resected group (p<0.0001). Multivariate analysis demonstrated improved survival for surgically resected patients (HR 0.7, p<0.0001), controlling for age, gender, and stage. Conclusions: Surgical resection was associated with improved survival when controlling for age, stage, and gender. However, the rate of surgical resection was much lower in the community when compared to tertiary referral centers. Treatment efforts should be focused on a multidisciplinary approach which includes surgical evaluation. No significant financial relationships to disclose.

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Disparities in receipt of radiotherapy and survival by age, sex, and race among patients with nonmetastatic squamous cell carcinoma of the anus.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.721 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 721-721

Author(s):

Doug Baughman ◽

Krishna Bilas Ghimire ◽

Binay Kumar Shah

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Survival Rates ◽

Relative Survival ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

P Value ◽

Hazards Model ◽

To Receive

721 Background: Combination chemoradiotherapy is the standard of care for treatment of non-metastatic squamous cell carcinoma of the anus (SCCA). This population-based study evaluated disparities in receipt of radiotherapy (RT) and its effect on survival in patients with localized and regional SCCA in the United States. Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 database was used to identify patients with localized and regional SCCA diagnosed between 1998 and 2008. We used univariate and multivariate logistic regression to model the relationships between receipt of RT and age, sex, marital status, stage, and race. Relative survival rates were calculated and compared using two sample z-tests. A Cox proportional hazards model was used to find adjusted hazard ratios (HR). Results: A total of 3,971 patients with localized or regional SCCA as the only primary malignancy were included in the study, of which 3,278 (82.6%) received RT. After adjusting for covariates, those 65 years and older (adjusted OR 0.82, p=0.029) were less likely to receive RT. Females were more likely to receive RT compared to males (adjusted OR 1.54, p<0.001). We found no difference in receipt of RT by race. Comparisons of 1- and 5-year relative survival rates showed lower survival for blacks (p-value <0.01 at 1-year and <0.0001 at 5-years), those 65 years and older, and males. A 1-year survival disparity was found for those not receiving RT (p-value <0.0001 at 1-year), but no difference was observed at 5-years. A Cox proportional hazards model adjusting for all covariates showed greater hazard for blacks (adjusted HR 1.36, p=0.001), those not receiving RT (adjusted HR 1.23, p=0.03), patients 65 years or older, and males. Conclusions: This population based study identified older patients as less likely to receive RT and females as more likely to receive RT. Survival analysis identified blacks, males, older patients, and those not receiving RT as having lower rates of survival.

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Narrowing of the Racial Disparities Gap in Survival of Patients with Mycosis Fungoides: A Longitudinal Analysis of the SEER Database (1988 to 2011)

Blood ◽

10.1182/blood-2021-151820 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1392-1392

Author(s):

Noha Soror ◽

Hamid D. Ismail ◽

Catherine Chung ◽

Basem M. William

Keyword(s):

Racial Disparities ◽

Research Funding ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

P Value ◽

Time Period ◽

Black Patients ◽

Over Time

Abstract I ntroduction: Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphomas. Prior Studies have identified Black race as a risk factor for earlier age at diagnosis, more advanced stages at time of diagnosis and poor prognosis in patients with MF. Data examining differences in racial disparities outcomes over time are limited. Objective: This retrospective analysis aims to examine if the racial disparities in survival outcomes of MF patients have improved over time. Subjects and Methods: Using the United States Surveillance, Epidemiology and End Results (SEER) 1988-2011 public use database, we examined survival patterns for patients with MF (with the code of 9700) between 1988 and 2011. Cases were divided into three cohorts based on the year of diagnosis; "1988 - 1995", "1996 - 2003", and "2004 - 2011". Univariable and multivariable analysis were conducted to assess for factors significantly associated with the overall survival. The nonparametric estimates of the survival distribution function, Kaplan and Meier survival curves, and Cox proportional hazards model were used to investigate the factors affecting the survival time. Results: From 1988 to 2011, a total of 2896 cases of MF were identified with a median follow-up of 60 months. The difference in the survival time between the years of diagnosis 1988-1995 and 2004-2011 is significant (p-value=0.05). The parameter estimate of the Cox proportional hazards model for the "1988-1995" and the "2004-2011" period as a reference is also significant (p-value = 0.024) and the hazard ratio (HR) is 1.407, which means that patients diagnosed in 1988-1995 were 1.4 times likely to die from the disease compared to the patients diagnosed in 2004-2011 (i.e. patients in 1988-1995 were more likely to not survive than in 2004-2011) (Table 1 and 2). There is no significant difference in the survival of the patients between "1996-2003" and "2004-2011" (p-value 0.998), Cox model estimate is not significant (p-value = 0.178), and the HR is 0.94 (Table 1 and 2). For the time period 1988-1995, the survival of Black patients was inferior to White (p= 0.0339), Asians (p=0.001), and other races (p=0.0011); Figure 2 and Table 3. For the time period 1996-2003, there was no difference in survival across races (p-value=0.7599); Figure 3 and Table 3. For the time period of 2004-2011, survival of Black patients was similar to White (p-value=1) but again inferior to Asian (p-value=0.05) and other races (p-value=0.09); Figure 4 and Table 3. Across the entire time period of 1998-2011, the survival of Black patients was inferior to White (Chi-square=6.59 and p-value=0.0084); Figure 5. The survival gap between Black and White patients seems to be obliterated in subsequent; "1996 - 2003" and "2004 - 2011" vs 1988-1995 (Figures 3 and 4) due to improvements in survival of Black patients over time (Figure 6) while the survival of White patients remained rather steady over time (Figure 7). Conclusions: Our study demonstrated that Black race was significantly correlated with poorer survival in patients with MF. The etiology of this poorer prognosis can be related to access to medical care, socioeconomic disparities, or possibly difference in disease biology and immune response. Despite the persistent pattern of lower survival across all time periods, the gap in survival between White and Black races seems to be narrowing overtime. Figure 1 Figure 1. Disclosures William: Dova Pharmaceuticals: Research Funding; Incyte: Research Funding; Kyowa Kirin: Consultancy; Merck: Research Funding; Guidepoint Global: Consultancy.

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Prognosis of Stage IIB early gastric cancer has a unique and dismal property putatively requiring post operative adjuvant chemothrapy

International Surgery ◽

10.9738/intsurg-d-15-00177.1 ◽

2017 ◽

Author(s):

Hideki Ushiku ◽

Keishi Yamashita ◽

Akira Ema ◽

Natsuya Katada ◽

Kei Hosoda ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factors ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer Prognosis ◽

Node Metastasis ◽

Dismal Prognosis

Abstract Background Pathological T1 (pT1) gastric cancer showed excellent prognosis, however lymph node metastasis sometimes reflects patients with dismal prognosis. In this study, we investigated prognosis of pT1 gastric cancer with lymph node metastasis to identify prognostic factors. Patients and Methods Among 1,442 gastric cancer patients between 2002 and 2010, 73 (5%) of pT1 with lymph node metastasis were identified. Univariate prognostic factors were applied to multivariate Cox proportional hazards model. Results (1) Among the 1,442 patients, pT1 was composed of 333 patients with pT1a and 423 patients with pT1b, which included 9 (2.7%) and 64 cases (15.1%) with lymph node metastasis, respectively. (2) Ten (13.7%) patients of the 73 patients with lymph node metastasis showed tumor relapse.　　Univariate negative prognostic factors were tumor size (p=0.03), intraoperative bleeding (p=0.03), and perioperative transfusion (POT)(p=0.001), as well as 14th JGCA Stage (p<0.0001), and multivariate analysis identified 14th JGCA Stage (p=0.0004) and POT (p=0.03) as independent prognostic factors. (3) pT1 gastric cancer representing pN3 (Stage IIB) was rare (n=4) and unique entity from a prognostic point of view, exhibiting dismal prognosis (0% at 5 years). We thereafter identified 17 such cases from 5,204 gastric cancer including the earliest cases. Prognosis of such 17 patients was very unique, in that recurrences occurred even 5 years after curative operation, and the frequent recurrent sites were bone. Conclusion pT1 gastric cancer prognosis is robustly affected by pN3 and POT, and Stage IIB disease showed unique prognosis requiring special attention even after 5 years of operation.

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