Development of a prognostic risk model for small cell lung cancer: Identification of high-, intermediate-, and low-risk cohorts based on clinical-genomic data.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8554-8554
Author(s):  
Fatemeh Ardeshir-Larijani ◽  
Gary Wildey ◽  
Pingfu Fu ◽  
Afshin Dowlati
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Model ◽  
Cox Regression ◽  
Cox Model ◽  
Prognostic Index ◽  
Low Risk ◽  
Intermediate Risk ◽  
Entire Cohort ◽  
Clinical Genomic

8554 Background: Although many clinical prognostic factors for SCLC outcome have been described, there are no models that incorporate the combination of clinical and genomic details into a risk model defining high and low risk patients. Methods: From a total of 791 SCLC patients seen between 2013-2018, 91 were evaluated by exome sequencing. Using the univariate Cox regression model, 19 genes were prognostic for survival and included RET, ERBB4 MAP3K1, ABL1, CCND1, TSC1, PRKCI, FGFR3, JAK3, ZNF217, BRCA1, GPR124, LRP1B, GNAS, TAF1, FGF3, STAT3, CD79A and FLT. LASSO, elastic-net Cox and traditional Cox model with stepwise selection along with traditional clinical factors (age and stage) were further used to build the final model. The final risk groups were defined based upon the prognostic index from multivariable Cox model involving age, stage (extensive/limited) and 6 genes ( MAP3K1, ABL1, CCND1, PRKCI, BRCA1, GNAS). Results: The overall survival (OS) for the entire cohort was 11.2 (95% CI: 9 – 13.4) months and the median age was 65 (range: 39 - 90) years. Eighty percent (N = 74) of evaluated patients had extensive stage (ES) disease. The HR for death of age and stage (ES/LS) was 1.06 (CI: 1.03-1.08, p < 0.0001) and 4.33 (CI: 2.23-8.41, p < 0.0001) respectively. ABL1 demonstrated the highest HR of 10.14 (2.81-36.6, p = 0.0004) followed by PRKCI (HR: 5.05, CI: 1.43-17.8 , p < 0.012), CCND1 (HR: 4.52, CI: 1.23-16.57, p < 0.023), MAP3K1 (HR: 3.38, CI: 1.37- 8.33, p = 0.008) and GNAS (HR: 2.21, CI: 1.11-4.43, p < 0.025). Interestingly, BRACA1 mutation was protective as patients with BRACA1 mutation had significantly better overall survival (HR: 0.3, CI: 0.1- 0.85, p < 0.023). Our model categorized patients into three groups of low risk ( N= 31), intermediate risk ( N= 30) and high risk ( N= 30) with significantly different survival outcomes ( p < 0.0001). Those with low risk had the median OS of 27.4 (95% CI: 16.8-55.5) months, intermediate risk with median OS of 10.8 (95% CI: 7 – 14.7) months and high risk with median OS of 5.4 (95% CI: 3.9- 9) months. Conclusions: This clinical-genomic risk group stratification represents a useful model to estimate SCLC survival outcome and may have value in future clinical trials.

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.

scholarly journals Treatment Outcome and a Practical 10-Point Prognostic Index in Adult Patients with Non-M3 Acute Myeloid Leukemia: A Retrospective, Multicenter Study in Malaysia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2606-2606
Author(s):  
Tze Shin Leong ◽  
Sen Mui Tan ◽  
Lee Ping Chew ◽  
Tee Chuan Ong ◽  
Siew Lian Chong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Outcome ◽  
High Risk ◽  
Relapse Rate ◽  
Survival Benefit ◽  
Risk Group ◽  
Prognostic Index ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk

Background: Literature on Acute Myeloid Leukemia (AML) survival and prognostic factors were often derived from strict trial studies from developed country. A simple yet practical prognosis index has not been developed and tested in resource limited setting such as Malaysia. We described the treatment outcome and designed a 10 point prognostic index to predict survival of adult AML (non-M3) in real clinical practice in Malaysia. Methods: Data were retrospectively collected and analyzed from all adults with AML diagnosed and treated from 2007 to 2017 in three main hematology centers in Malaysia, Ampang Hospital, Sarawak General Hospital and Miri General Hospital. Treatment pattern and survival outcome were described. Multivariable analysis using Cox regression statistics were performed to identify significant prognostic variables affecting overall survival. Each variable were assigned points based on hazard ratios. A sum of the points led to a maximum score of 10. Patients were then categorized into low (0 point), intermediate (1 to 3 points) or high-risk group (4 points or above). Results: Demographics and treatment outcome of patients are shown in Table 1 & 2. There were 1277 adult patients, diagnosed with AML where 86.5% (n= 1106) of them were non M3 AML. Out of these, 908 patients (82.2%) received intensive chemotherapy treatment. Median age of diagnosis was 45 years. The remission post induction rate was 64.3% with induction death, refractory and relapse rate of 8.8%, 20.0% and 27.7% respectively. Median overall survival (OS) and Event Free Survival (EFS) time was 15 months and 12 months. The 3-year OS and EFS was 32.9% and 28.5% respectively. At the time of analysis, 66.1% of patients were dead (n=600) with disease progression being the main cause of death (n=416, 45.8%). Three year overall OS for patients who underwent allogeneic stem cell transplant (n=301, 33.1%) versus patients without transplantation were 53.7 % versus 22.0 % (HR 2.597, p <0.001). Cumulative incidence of relapsed and non-relapse mortality for transplant patients, shown in Figure 1 were 27.5% and 22.1%. Multivariate analysis in Table 3 showed that age 60 years old and above, male gender, white cell count more than 100 x 109 /L ,relapsed less than 12 months of treatment, refractory state after induction and high risk genetic group (based on EuropeanLeukemiaNet/Medical Research Council risk stratification by genetics) are prognostic factors associated with worse OS and EFS. The information was used to develop a 10 point prognostic index based on calculation described in Table 3. Overall survival decreased with each additional index point. When stratified according to risk group, the 3 year OS for low risk, intermediate risk and high risk group was 53.3%, 34.3% and 4.9% respectively. This is shown in Table 4 & Figure 2. Relapse rate was also lower in the low-risk group (8.8%), compared to intermediate-risk group (19.2%) and high-risk group (35.2%). Comparing transplant and non transplant cohort shown in Figure 3, there was no survival benefit in the low-risk group (58.6% vs 49.2%, p=0.122) but significant survival benefit in both intermediate-risk group (56.6% vs 23%, p<0.001) and adverse-risk group (13% vs 7%, p=0.002). Discussion/Conclusion: This is one of few survival studies that involved patients of different ethic groups in Asia (Malay, Chinese, Indian and native Borneo Sarawakians). Our results are comparable to data from large population based database such as US SEER and EURO CARE. This is the first prognostic index incorporating genetics, baseline characteristics and dynamic response, eg. refractory and/or relapsed post induction in non M3 AML. The results reaffirmed the importance of these factors in determining the clinical outcome and prognosis of patients with AML. When stratified using our 10 point prognostic index, our cohort of patients who is in low risk group has lower relapse rate and did not have significant survival benefit from allogeneic transplant compare to stratification using only the ELN/MRC genetic classification.(Table 5 & 6). In resource limited setting, measurable residual disease (MRD) monitoring and advanced genetic testing are difficult financially. This prognostic scoring index is an economical and practical alternative to guide physicians on treatment after induction therapy. However, it still needs to be validated by a larger cohort of patients in a prospective study. Disclosures No relevant conflicts of interest to declare.

Outcome of Patients (pts) with Low and Intermediate-1 Risk Myelodysplastic Syndrome (MDS) After Hypomethylating Agent (HMA) Failure.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2824-2824
Author(s):  
Elias J. Jabbour ◽  
Naval G. Daver ◽  
Tina (Xiao Qin) Dong ◽  
Tapan M. Kadia ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Overall Survival ◽  
Growth Factors ◽  
High Risk ◽  
Lower Risk ◽  
Risk Model ◽  
Survival Rates ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Disease ◽  
Overall Survival Rates

Abstract Abstract 2824 Background: HMA are standard of care in pts with high-risk MDS and commonly used in pts with lower risk. Pts with high-risk disease post HMA failure have a poor prognosis with a median survival of 4 months (Jabbour et al. Cancer. 2010;116:3830–4). The prognosis of patients with low and intermediate-1 risk MDS after HMA failure is not known. Aims: To assess survival in patients with low and intermediate-1 risk disease at the time of HMA failure that might benefit from specific strategies or investigational agents. Methods: Data from 699 patients with MDS (n=397) and chronic myelomonocytic leukemia (n=302) treated with HMA at one institution between 2000 and 2011 were reviewed. 126 (18%) of them were of low and intermediate-1 risk disease by IPSS score. Results: A total of 30 (24%) patients with MDS (n=26) and CMML (n=4) who had failed HMA therapy and remained of low and intermediate-1 risk disease were analyzed. These included 6 patients with low- and 24 intermediate-1 risk disease. Eleven patients had secondary disease. At the start of HMA, 22 patients were low-risk and 8 were intermediate-1 risk disease. Seventeen patients had a diploid cytogenetic analysis. Seven and 23 patients received azacitidine and decitabine, respectively. These patients had discontinued HMA because of primary resistance in all patients. The characteristics of the study group are shown in Table 1. Upon HMA failure, 24 (80%) were low-risk disease and 6 (20%) intermediate-1-risk disease. A total of five (17%) patients transformed subsequently into acute myeloid leukemia. After a median of 18 months from HMA failure, 12 (40%) patients remained alive. The median overall survival was 22 months with estimated 1- and 2-year overall survival rates of 65% and 45%, respectively. Considering overall survival from the start of HMA therapy, the median survival was 29.5 months with estimated 1- and 2-year overall survival rates of 80% and 60%, respectively. The 30 patients with HMA failure were subsequently assessed by the lower-risk MDACC risk model (Garcia-Manero et al. Leukemia. 2008;22:538–43): 8 (27%) had low-risk, 8 (27%) intermediate-risk, and 14 (46%) high-risk disease. Their 1-year survival rates were 66%, 73%, and 86%, respectively. Considering survival from the time of the initiation of HMA therapy, the estimated 1-year survival rates were 60%, 70%, and 100%, respectively, for patients with high-risk, intermediate-risk, and low-risk disease according to the MDACC risk model. After HMA failure, 11 (37%) patients received salvage investigational therapy, of whom 3 responded with 2 achieving hematologic improvement for a median of 12 months (range, 5–19) and one patient achieving a complete remission for 14 months that was lost thereafter, 1 (3%) received immunotherapy, 1 (3%) received growth factors only, and 17 (57%) elected not to receive any further treatment. No response was observed in the 2 patients who received subsequent immunotherapy or growth factors. Conclusion: The outcome of patients with low and intermediate-1 risk MDS after HMA failure is poor and appears to be predictable. Disclosures: Ravandi: Genzyme/Sanofi: Honoraria. Faderl:Genzyme: Advisory Board Other, Research Funding.

scholarly journals Chinese External Validation of the Cochrane Haematological Malignancies Group Prognostic Index for Chronic Lymphocytic Leukemia Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5280-5280
Author(s):  
Shu Chao Qin ◽  
Wei Xu ◽  
Yi Xia ◽  
Chun Qiao ◽  
Lei Fan ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Prognostic Index ◽  
Risk Groups ◽  
Low Risk ◽  
Clinical Staging ◽  
Intermediate Risk ◽  
Haematological Malignancies ◽  
Risk Scoring ◽  
Very High

Abstract Objection: Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disease characterized by highly clinical and biological heterogeneity. A number of biomarkers have been identified in predicting the overall survival (OS) over the last decades besides the traditional clinical staging. Recently, an international prognostic index (IPI) combing clinical staging and biomarkers was developed by the investigators of the Cochrane Haematological Malignancies Group. Due to genetic differences between Caucasic and Chinese CLL patients, our study was to validate the guiding function of IPI on Chinese CLL cases. Method: We performed a validation of the IPI proposed by the Cochrane Haematological Malignancies Group to stratify Chinese CLL patients prognostically in 225 CLL cases registered at our center. The five parameters (age, TP53 abnormalities, IGHV mutation status, b2-microglobulin and Binet stage) involved in the IPI were collected by clinical data, serum test, PCR and fluorescence in situ hybridization (FISH). Chi-square test, survival analysis, log-rank test and cox hazard regression analysis were utilized in the validation. Result: In the 225 Chinese CLL cases analysed in the validation, all five parameters involved in the IPI were associated with overall survival (OS) independently. The multivariate analysis demonstrated that age above 65 years old (HR 2.22; [1.15-4.30]; P=0.018), b2-microglobulin over 3.5 mg/L (HR 2.46; [1.22-4.94]; P=0.001), Binet staging B/C (HR 3.40; [1.02-11.33]; P=0.046), TP53 abnormalities (HR 2.72; [1.50-4.94]; P=0.012) and IGHV unmutation (HR 5.19; [2.51-10.77]; P<0.001) were OS related risk factors respectively. Then a total point score was calculated for each patient according to the grading system proposed by the Cochrane Haematological Malignancies Group investigators. There were 60 (26.7%) patients at low-risk (scoring 0-1), 57 (25.3%) patients at intermediate-risk (scoring 2-3), 65(28.9%) patients at high-risk (scoring 4-6) and 43 (19.1%) patients at very high-risk (scoring 7-10). The IPI allowed different prediction of time to treatment (TTT) in all groups (Fig. 1). The estimated median TTT were: 102 months for low-risk, 12 months for intermediate-risk and 1 month for high-risk group. However, the low-risk and intermediate-risk groups showed similar overall survival (P=0.424). Beyond that, significant difference was found between the intermediate, high and very high-risk groups. We combined the low-risk and the intermediate-risk groups into one to accommodate to the Chinese CLL cases. 117 (52%) patients were at low & intermediate-risk (scoring 0-3), thus leading to the significantly different prognostic value between groups (Fig. 1) . The estimated median survival times were: not reached for low&intermediate-risk, 63 months for high-risk and 128 months for very high-risk group. Conclusion: Our results basically validated the IPI proposed by the Cochrane Haematological Malignancies Group to prognostically stratify CLL patients in China, which confirmed the value of the novel prognostic index externally. However, a slight adaption was made to accommodate the Chinese cases better via the combination of the low-risk and intermediate-risk groups. We considered that a universally recognized prognostic model would be utilized to predict the disease progression and guide the treatment when initially diagnosed. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

2020 ◽  
Author(s):  
Yi Ding ◽  
Tian Li ◽  
Min Li ◽  
Tuersong Tayier ◽  
MeiLin Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Model ◽  
Risk Group ◽  
Clinical Information ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Positive Regulation ◽  
Risk Patients ◽  
Cox Analysis

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

A Validated Risk Model for Prediction of Early Readmission in Patients with Hepatic Encephalopathy

2018 ◽  
Vol 17 (5) ◽  
pp. 0-10
Author(s):  
Andrew J. Kruger ◽  
Fasika Aberra ◽  
Sylvester M. Black ◽  
Alice Hinton ◽  
James Hanje ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Hepatic Encephalopathy ◽  
High Risk ◽  
Risk Model ◽  
Cox Regression ◽  
Low Risk ◽  
Assessment Model ◽  
Risk Assessment Model ◽  
Early Readmission ◽  
The Impact

Introduction and aim. Hepatic encephalopathy (HE) is a common complication in cirrhotics and is associated with an increased healthcare burden. Our aim was to study independent predictors of 30-day readmission and develop a readmission risk model in patients with HE. Secondary aims included studying readmission rates, cost, and the impact of readmission on mortality. Material and methods. We utilized the 2013 Nationwide Readmission Database (NRD) for hospitalized patients with HE. A risk assessment model based on index hospitalization variables for predicting 30-day readmission was developed using multivariate logistic regression and validated with the 2014 NRD. Patients were stratified into Low Risk and High Risk groups. Cox regression models were fit to identify predictors of calendar-year mortality. Results. Of 24,473 cirrhosis patients hospitalized with HE, 32.4% were readmitted within 30-days. Predictors of readmission included presence of ascites (OR: 1.19; 95% CI: 1.06-1.33), receiving paracentesis (OR: 1.43; 95% CI: 1.26-1.62) and acute kidney injury (OR: 1.11; 95% CI: 1.00-1.22). Our validated model stratified patients into Low Risk and High Risk of 30-day readmissions (29% and 40%, respectively). The cost of the first readmission was higher than index admission in the 30-day readmission cohort ($14,198 vs. $10,386; p-value < 0.001). Thirty-day readmission was the strongest predictor of calendar-year mortality (HR: 4.03; 95% CI: 3.49-4.65). Conclusions. Nearly one-third of patients with HE were readmitted within 30-days, and early readmission adversely impacted healthcare utilization and calendar-year mortality. With our proposed simple risk assessment model, patients at high risk for early readmissions can be identified to potentially avert poor outcomes.

A Critical Analysis of Prognostic Factors in Patients with HTLV-1 Adult T-Cell Leukemia/Lymphoma: A Multicenter Clinicopathologic Experience and New Prognostic Score.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1784-1784
Author(s):  
Adrienne A. Phillips ◽  
Iuliana Shapira ◽  
Robert D. Willum ◽  
Jasotha Sanmugarajah ◽  
William B. Solomon ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Median Survival ◽  
Risk Group ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Prognostic Index ◽  
Low Risk ◽  
Intermediate Risk ◽  
A Performance

Abstract Purpose: Adult T-Cell Leukemia/Lymphoma (ATLL) is a rare aggressive Human T-cell Lymphotropic Virus Type-I (HTLV-I) associated peripheral T-cell neoplasm with 4 recognized clinicopathologic subtypes: acute, lymphomatous, chronic, and smoldering. Since the initial description of these variants, several studies have sought to identify additional prognostic factors. We assessed prognostic models already in use for aggressive non-Hodgkin lymphomas to develop a novel risk stratification scheme. Methods: Data regarding patients with ATLL were collected from 3 medical centers between 8/92 and 5/07. Descriptive statistics were used to assess categorical and continuous variables. Overall survival (OS) was defined as time from diagnosis to death. Survival curves for OS were estimated using the Kaplan-Meier method. Univariate associations between individual clinical factors and OS were evaluated using the log-rank test for categorical variables and the Cox model for continuous variables. Maximum logrank analysis was used to select the optimal cut-off for calcium. In order to develop a simple risk model and allow for interactions of factors independently associated with OS, we used recursive partitioning analysis. Results: 89 patients with ATLL were identified; 37 males (41.6%) and 52 females (58.4%) and median age 50 years (range 22 to 82). The acute subtype of ATLL predominated (68.5%), followed by lymphomatous (20.2%), chronic (6.8%) and smoldering (4.5%). Median OS for all sub-types was 24 weeks (range 0.9 to 315). According to the International Prognostic Index (IPI), 8 patients (9.1%) were classified as low risk, 11 patients (12.5 %) as low intermediate risk, 13 patients (14.8 %) as high intermediate risk, and 56 patients (63.6 %) as high risk, 1 patient could not be evaluated due to missing data. Median OS by IPI risk group was 271, 65, 31 and 16 weeks, respectively (p&lt;0.01). The Prognostic Index for PTCL-U (PIT) could be determined in 68 patients; 10 patients (14.7 %) had a score of 0–1 (group 1), 19 patients (27.9 %) had a score of 2 (group 2), 31 patients (45.6 %) had a score of 3 (group 3), and 8 patients (11.8 %) had a score of 4 (group 4). Median OS by PIT risk group was 61.1, 28, 24, and 11.3 weeks respectively (p&lt;0.01). A new risk model was developed using the variables of the IPI and PIT. In addition, calcium level at diagnosis was also included as it had independent prognostic value. Recursive partitioning of OS based on these variables gave a tree with 5 nodes, which fell into three risk categories: low risk patients with Stage I–II disease and a performance status &lt;2; the medium risk group composed of two sets of patients: those with Stage III–IV disease with an ECOG performance status &lt; 2 or those with an ECOG performance status ≥ 2 with calcium ≤ 11 mg/dL and age ≤ 60; and the high risk group (also comprising 2 sets of patients): those with a performance status ≥ 2 with calcium ≤ 11 mg/dL and age &gt; 60 or those with a performance status ≥ 2 and calcium &gt; 11 mg/dL. There were 10 patients (11.2%) in the low risk (median survival= 156.6 weeks), 31 (34.8%) in the intermediate risk (median survival = 45.4 weeks), and 48 (53.9%) in the high risk (median survival= 13 weeks) categories (p&lt;0.01). Conclusion: This retrospective series confirms a poor outcome for North American patients with HTLV-1 related ATLL. Although the IPI and PIT identified subsets of patients, these models had liabilities. We propose a new prognostic model based on recursive partitioning analysis that successfully identifies three prognostic categories based on performance status, stage, age and calcium level at diagnosis in a more robust and distinct fashion. Table 1. Comparison of Prognostic Scores and Kaplan Meier Survival Estimates (%) of patients with ATLL International Prognostic Index (IPI) (n = 88) Prognostic Index for PTCL-U (PIT) (n = 68) ATLL Prognostic Score (APS) (n= 89) Time (wks) Low n= 8 Low-Intermed n= 11 High-Intermed n= 13 High n= 56 Group 1 n= 10 Group 2 n= 19 Group 3 N= 31 Group 4 n= 8 Low n= 10 Intermed n= 31 High n= 48 13 8 (100%) 10 (100%) 9 (75.5%) 31 (53.1%) 10 (100%) 13 (68.4%) 19 (66.3%) 3 (25.0%) 9 (100%) 27 (87.1%) 23 (46.4%) 26 8 (100%) 9 (90.0%) 6 (56.6%) 17 (31.1%) 10 (100%) 9 (51.3%) 13 (45.4%) 0 (0%) 9 (100%) 23 (77.0%) 9 (19.9%) 52 6 (75.0%) 6 (60.0%) 3 (28.3%) 9 (17.6%) 5 (50%) 5 (28.5%) 8 (30.7%) 0 (0%) 8 (88.9%) 13 (46.0%) 4 (8.8%) 78 5 (75.0%) 4 (40.0%) 2 (18.9%) 2 (4.0%) 4 (40%) 3 (17.1%) 2 (7.7%) 0 (0%) 7 (88.9%) 7 (24.8%) 0 (0%) 104 3 (56.2%) 3 (30.0%) 2 (18.9%) 2 (2.0%) 2 (30%) 3 (17.1%) 2 (3.8%) 0 (0%) 4 (61.0%) 6 (17.7%) 0 (0%) Median OS (wks) 271 65 31 16 61.1 28 24 11.3 156.6 45.4 13

Value of clinical treatment score post-5 years (CTS5) for late relapse risk assessment in patients with early-stage HER2+ breast cancer (BC) in the north central cancer treatment group (NCCTG) N9831 (Alliance) trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 529-529
Author(s):  
Tanmayi Pai ◽  
Angelica Gil ◽  
Yaohua Ma ◽  
Zhuo Li ◽  
Pooja Advani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Tumor Size ◽  
Cox Regression ◽  
Early Stage ◽  
Low Risk ◽  
Late Relapse ◽  
Intermediate Risk ◽  
Relapse Risk ◽  
Significant Difference

529 Background: Multiple prognostic models exist to predict late relapse risk in early stage hormone receptor-positive (HR+) breast cancer (BC). The CTS5 is one such model that has been validated in HR+ HER2-negative BC. The value of this model in HR+ HER2+ has not been established. Here, we assessed CTS5 in patients (pts) with early stage HER2+ BC treated in the NCCTG N9831 (Alliance) trial. Methods: Pts with stage I-III HER2+ HR+ BC who survived ≥ 5 years were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. Results: From 3,130 pts, 1,204 pts met the criteria and were included. Median age was 49 (22-79) years and median tumor size was 2.4 (0.1-12) cm. 63.6% had grade 3 tumors, 33.6% grade 2, and 2.8% grade 1. Median follow up was 10.89 (5.01-15.32) years. Based on CTS5, 821 (68.2%) pts were classified as high risk, 289 (24%) as intermediate risk, and 94 (7.8%) as low risk. Overall, using univariate Cox regression analysis, there was no statistically significant difference in recurrence free survival (RFS) among pts with intermediate vs. low (HR 0.47 95%CI 0.18-1.22, p = 0.12) and high vs. low (HR1.23 95%CI0.57-2.67, p = 0.6) with the C index of 0.58. Among pts who received concurrent trastuzumab (H) with HR+ BC, there was also no statistical difference in RFS between high vs. low (HR 0.68 95%CI0.24-1.97, p = 0.48) with the C index of 0.55. Paradoxically, pts with intermediate risk had better RFS than low risk (HR 0.18 95%CI0.03-0.97, p = 0.05). As a continuous variable, there is also no significant improvement in RFS per 1 unit increase in CTS5 score (HR 1.19 95%CI 0.73-1.96, p = 0.49) with the C index of 0.54. After 5 years, 7.06% (n = 30/425) of HR+ pts treated with concurrent H recurred. Conclusions: The CTS5 model is not prognostic in pts with early stage HR+ HER2+ BC receiving adjuvant H. While most HR+ HER2+ pts are classified as high risk by CTS5, the recurrence between years 5-10 was low in pts who received adjuvant H. This study highlights the need to develop a new predictive model for risk of late relapse in this specific group of pts to enable clinicians to determine which pts would benefit from extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, Genentech. https://acknowledgments.alliancefound.org Clinical trial information: NCT00005970 .

scholarly journals Serbian lymphoma study group: Demografic characteristics of 257 patients with follicular lymphoma

2015 ◽  
Vol 72 (6) ◽  
pp. 483-488
Author(s):  
Olivera Simonovic ◽  
Lana Macukanovic-Golubovic ◽  
Bosko Andjelic ◽  
Darko Antic ◽  
Biljana Mihaljevic
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Treatment Decision ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Prognostic Groups

Background/Aim. Follicular lymphoma (FL) is a B-cell tumor usually with indolent clinical course, yet in some cases the course of the disease can be very aggressive. The aim of the re-search was to determine distribution of patients into prognostic groups based on the International Prognostic Index (IPI) and Folicular Lymphoma International Prognostic Index (FLIPI) criteria, as well as to determine the importance of classifying patients into the prognostic groups, since this could potentially have the influence on selection of the treatment modality. Methods. The retrospective study was performed on 257 patients with follicular lymphoma diagnosed between January 2000 and April 2011. Results. Based on the IPI score, 153 (59.53%) patients had low risk, 57 (22.18%) low intermediate risk, 15 (5.84%) high intermediate risk, 9 (3.50%) high risk, whereas the classification of 23 patients diagnosed with FL remained with unknown risk according to the IPI. Based on the FLIPI prognostic index, 113 (43.97%) patients had low risk, 70 (27.24%) intermediate risk and 51 (19.84%) high risk, whereas the classification of 23 (8.95%) patients remained unknown. On the basis of the FLIPI 2 prognostic index, 48 (18.68%) patients had low risk, 145 (56.42%) intermediate risk and 41 (15.95%) high risk. The classification into prognostic groups for 23 (8.95%) patients remained unknown. According to the IPI, FLIPI and FLIPI 2 there were the patients that required treatment in all the risk groups. Conclusion. The FLIPI and FLIPI 2 effectively identify patients at high risk, thus helping in treatment decision for each single patient.

scholarly journals Comprehensive analysis of the significance of ferroptosis-related genes in the prognosis and immunotherapy of oral squamous cell carcinoma

2020 ◽  
Author(s):  
Junhao Yin ◽  
Xiaoli Zeng ◽  
Zexin Ai ◽  
Miao Yu ◽  
Yang'ou Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Oral Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
Regression Analyses

Abstract Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease that emerged as a major international health concern, associated with poor prognosis and the absence of specific biomarkers. Studies have shown that the ferroptosis-related genes (FRGs) can be used as tumor prognostic markers. However, FRGs’ prognostic value in OSCC needs further exploration. Our aim was to construct a novel FRG signature for overall survival (OS) prediction in OSCC patients and explore its role in immunotherapy.Methods: In our study, gene expression profile and clinical data of OSCC patients were collected from a public domain. FRGs were available from the FerrDb database. We performed univariate and multivariate Cox regression analyses to construct a multigene signature. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) methods were utilized to test the effectiveness of the FRG signature. A differential gene expression analysis was performed by the limma R package, followed by functional enrichment analyses. CIBERSORT was applied to analyze the tumor microenvironment (TME). Finally, the expression of human leukocyte antigen (HLA) and immune checkpoint molecules were analyzed to confirm the sensitivity of immunotherapy.Results: A total of 103 FRGs, expressed in OSCC (FRGs-OSCC), were identified from the two datasets by the Venn analysis. The Cox regression analysis identified 5 FRGs-OSCC that were associated with overall survival (all P < 0.01). The FRGs-OSCC risk model was established to classify patients into high risk and low risk groups. Compared with the low risk group, the survival time of the high-risk group was significantly reduced (P < 0.001). According to the multivariate Cox regression analyses, the risk score acted as an independent predictor for OS (HR > 1, P < 0.001). The accuracy of the FRGs-OSCC risk predictive model was confirmed by ROC curve analysis. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed significant enrichment of immune-related pathways, and a difference in tumor microenvironment between the two groups. The low risk group had the characteristics of higher expression of HLA and immune checkpoints (IDO1, LAG3, PDCD1 and TIGHT), a lower tumor purity and a higher infiltration of immune cells, indicating a more sensitive response to immunotherapy.Conclusions: The novel FRGs-OSCC risk score system can be used to predict OSCC prognosis. Ferroptosis targeting may be a therapeutic option for OSCC.

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