scholarly journals Evaluation of Early Treatment Response Utilizing the MAS-ALL18 Adapted Management Guideline in Four "Mexico in Alliance with St. Jude" (MAS) Member Hospitals

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1210-1210
Author(s):  
Hugo Romo ◽  
Pablo Gonzalez-Montalvo ◽  
Daniela Arce ◽  
Dinora Aguilar-Escobar ◽  
Nataly Mercado ◽  
...  
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Risk Group ◽  
Group Classification ◽  
Induction Phase ◽  
Collaborative Network ◽  
Management Guideline ◽  
Cytogenetic Testing ◽  
Risk Treatment ◽  
Group Stratification

Abstract Introduction: Acute lymphoblastic leukemia (ALL) represents approximately 50% of all childhood cancers in Latin America. Mexico is not the exception. The impact of ALL survival on overall childhood cancer survival is significant. According to government data, five-year survival is about 52%. Mexico in Alliance with St. Jude (MAS) is a multi-site, intersectoral collaboration. The collaborative network has explored and reported on factors associated with this suboptimal outcome and have identified challenges with ALL risk group classification as a leading cause. For example, as many as 82% of children diagnosed with ALL in Mexico receive high-risk treatment and the tendency for higher-risk group assignment often occurs in response to limited access to cytogenetic testing and minimal residual disease (MRD) testing. This leads to higher intensity treatment and may explain the high rate of treatment-related death (TRD) (12%) documented during the induction but also subsequently. In our previous case series, only 75% of patients were alive at the end of the first year of treatment. These findings, led MAS to develop a consensus-derived standardized diagnosis and treatment schema (MAS-ALL18), which takes into account clinical, cytogenetic, and MRD results. Diagnostic testing is performed in a centralized laboratory. Although centred on delivery of standard of care, this experience represents is the first prospective multi-site cooperative group effort in Mexico. We report on early treatment (first 90 days) clinical and implementation outcomes utilizing the MAS-ALL18 adapted management guideline (AMG) in four member hospitals of the MAS collaboration network. Results: From June 2019 to June 2020, 137 patients received treatment utilizing the MAS-ALL18 AMG in four publicly funded hospitals in Mexico. B-cell ALL represented 91.9% of the cases, 20.4% of patients were older than 9 years of age, 25.5% had a white blood cell count greater than 50,000 at diagnosis and 58.3% were male. Complete remission at the end of the induction was achieved in 90.6% of patients. TRD during the induction phase was 8%. MRD at Day 15 in 123 patients with B-cell ALL, 84.5% of them had MRD <1% and 7.3% had MRD ≥5%. MRD at Day 29 was assessed for the 10 patients diagnosed with T-cell ALL, 4 patients had MRD <0.01%, 2 had 0.02%, and 4 died during the induction phase. MRD was also assessed during consolidation (at Day 84) in 99 patients, 94.9% had MRD <0.01% and 5 patients MRD ≥0.01%, from which 3 had MRD at day 15 >1% and none registered an MRD result <0.5%. Utilizing the MAS-ALL18 risk group stratification, 50% of patients were assigned to a favorable risk group at the end of the consolidation. In 34 patients, the risk group was reclassified following the standardized algorithm; 30 reclassification events happened at the end of the induction and four at the end of the consolidation. Only two events were reassigned to a lower risk group, while the rest of the reclassifications were conducted to assign patients to a higher risk group due to unfavorable cytogenetics or an inadequate early response to treatment. High-risk treatment was ultimately assigned to 30% of patients using the MAS-ALL18 risk classification schema. Conclusion: It is feasible to implement a standardized multi-site adapted management guideline for ALL risk group stratification and treatment allocation in Mexico in the context of a collaborative network. TRD remains high during the induction phase, nevertheless, this number shows an improvement (8%) compared to the 2015 data report (12%). The ALL risk group classification is transitioning from a rigid scheme that placed 80% of patients in a high-risk group to a dynamic classification system that considers cytogenetic testing and MRD conducted in a centralized and externally validated laboratory that serves as reference for all the participating hospitals. The standardized MAS-ALL18 approach allowed us to classify 50% of patients in a favorable risk group during and at the end of the induction phase, which implies receiving a lower intensity treatment with a high probability of cure and a lower risk of TRD. The implementation of MAS-ALL18 risk classification scheme reduced the number of children requiring high-risk treatment in the participating hospitals. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis

TH Open ◽  
2020 ◽  
Vol 04 (01) ◽  
pp. e59-e65 ◽  
Author(s):  
Alex C. Spyropoulos ◽  
Concetta Lipardi ◽  
Jianfeng Xu ◽  
Colleen Peluso ◽  
Theodore E. Spiro ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Risk Score ◽  
Lower Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Cutoff Score ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
D Dimer

AbstractAn individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding. This retrospective analysis investigated whether the modified IMPROVE VTE model with an elevated D-dimer could identify a high VTE risk subgroup of patients for ET from a subpopulation of the MAGELLAN study, which was previously identified as having a lower risk of bleeding. We incorporated the modified IMPROVE VTE score using a cutoff score of 4 or more or 2 and 3 with an elevated D-dimer (>2 times the upper limit of normal) to the MAGELLAN subpopulation. In total, 56% of the patients met the high-risk criteria. In the placebo group, the total VTE event rate at Day 35 was 7.94% in the high-risk group and 2.83% for patients in the lower-risk group. A reduction in VTE was observed with rivaroxaban in the high-risk group (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.51–0.91, p = 0.008) and in the lower-risk group (RR: 0.69, 95% CI: 0.40 -1.20, p = 0.187). The modified IMPROVE VTE score with an elevated D-dimer identified a nearly threefold higher VTE risk subpopulation of patients where a significant benefit exists for ET using rivaroxaban.

An Automated and Quantitative Protein Expression-Based Classification System to Identify High Risk Multiple Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 735-735
Author(s):  
Alex Klimowicz ◽  
Paola Neri ◽  
Adnan Mansoor ◽  
Anthony Magliocco ◽  
Douglas A. Stewart ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Protein Expression ◽  
Classification System ◽  
Risk Group ◽  
Univariate Analysis ◽  
High Risk Group ◽  
Group Classification ◽  
Low Risk ◽  
High Expression

Abstract Background: Autologous stem cell transplantation (ASCT) has dramatically improved the survival of myeloma patients; however, this approach has significant toxicities and nearly 25% of MM patients progress within one year from their transplant. While gene expression profiling-based (GEP) molecular classification has permitted the identification of unresponsive high-risk patients, these approaches have proven too costly and complex to translate into clinical practice. Less expensive and more readily available methods are needed clinically to identify, at the time of diagnosis, MM patients who may benefit from more aggressive or experimental therapies. While protein-based tissue arrays offer such alternative, biases introduced by the “observer-dependent” scoring methods have limited their wide applicability. Methods: We have designed a simplified, fully automated and quantitative protein expression based-classification system that will allow us to accurately predict survival post ASCT in a cost effective and “observer-independent” manner. We constructed tissue microarrays using diagnostic bone marrow biopsies of 82 newly diagnosed MM patients uniformly treated with a dexamethasone based induction regimen and frontline ASCT. Using the HistoRx PM-2000 quantitative immunohistochemistry platform, coupled with the AQUA analysis software, we have examined the expression of the following proteins: FGFR3 which is associated with t(4;14), cyclin B2 and Ki-67 which are associated with cellular proliferation, TACI which is associated with maf deregulation, and phospho-Y705 STAT3 and p65NF-κB, which are associated with myeloma cell growth and survival. For FGFR3, patients were divided into FGFR3 positive and negative groups based on hierarchical clustering of their AQUA score. For all other proteins examined, based on AQUA scores, the top quartiles or quintiles of patients were classified as high expression groups. Based on the univariate analysis, patients were further classified as “High Risk” MM if they had been identified as high expressers of either TACI, p65NF-κB or FGFR3. The Kaplan-Meier method was used to estimate time to progression and overall survival. Multivariate analysis was performed using the Cox regression method. Results: 82 patients were included in this study. In univariate analysis, FGFR3 and p65NF-κB expression were associated with significantly shorter TTP (p=0.018 and p=0.009) but not OS (p=0.365 and p=0.104). TACI expression levels predicted for worse OS (p=0.039) but not TTP (p=0.384). High expression of Ki67 or phospho-Y705 STAT3 did not affect survival. Of the 82 cases, 67 were included in the multivariate analysis since they had AQUA scores available for all markers: 26 (38.8%) were considered as High Risk by their AQUA scores and had significantly shorter TTP (p=0.014) and OS (p=0.006) compared to the Low Risk group. The median TTP for the Low and High Risk groups was 2.9 years and 1.9 years, respectively. The 5-years estimates for OS were 60.6% for the High Risk group versus 83.5% for the Low Risk group. Multivariate analysis was performed using del13q and our risk group classification as variables. Both our risk group classification and del13q were independent predictors for TTP, having 2.4 and 2.3 greater risk of relapse, respectively. Our risk group classification was the only independent predictor of OS with the High Risk group having a 5.9 fold greater risk of death. Conclusions: We have found that the expression of FGFR3, TACI, and p65NF-κB, in an automated and fully quantitative tissue-based array, is a powerful predictor of survival post-ASCT in MM and eliminates the “observer-dependent” bias of scoring TMAs. A validation of this “High Risk” TMA based signature is currently underway in larger and independent cohorts. Figure Figure

scholarly journals ANALYSIS OF INDUCTION PHASE GLUCOCORTICOID USE ON ADRENAL SUPPRESSION IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2017 ◽  
Vol 52 (1) ◽  
pp. 7
Author(s):  
Octaviana Simbolon ◽  
Yulistiani Yulistiani ◽  
I DG Ugrasena ◽  
Mariyatul Qibtiyah
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
High Risk Group ◽  
Adrenal Suppression ◽  
Induction Phase ◽  
Childhood All ◽  
Cortisol Levels ◽  
Standard Risk

Glucocorticoids play an important role in the treatment of acute lymphoblastic leukemia (ALL). However, supraphysiological doses may cause suppression of the adrenal. Adrenal suppression resulting in reduced cortisol response may cause an inadequate host defence against infections, which remains a cause of morbidity and mortality in children with ALL. The occurrence of adrenal suppression before and after glucocorticoid therapy for childhood ALL is unclear. The aim of this study is to analysis the effect of glucocorticoid on cortisol levels during induction phase chemotherapy in children with acute lymphoblastic leukemia. A cross-sectional, observational prospective study was conducted to determine the effect of glucocorticoid on cortisol levels in children with acute lymphoblastic leukemia. Patients who met inclusion criteria were given dexamethasone or prednisone therapy for 49 days according to the 2013 Indonesian Chemotherapy ALL Protocol. Cortisol levels were measured on days 0, 14, 28, 42 and 56 of induction phase chemotherapy. There were 24 children, among 31 children recruited, who suffered from acute lymphoblastic leukemia. Before treatment, the means of cortisol levels were 228.95 ng/ml in standard risk group (prednisone) and 199.67 ng/ml in high risk group (dexamethasone). In standard risk group, the adrenal suppression occurs at about day 56. There was a significant decrement of cortisol levels in high risk group in days 14, 28, 42 against days 0 of induction phase (p=0.001). Both groups displayed different peak cortisol levels after 6 week of induction phase (p=0.028). Dexamethasone resulted in lower cortisol levels than prednisone during induction phase chemotherapy in children with acute lymphoblastic leukemia.

scholarly journals TP6.2.17 How good is Edinburgh Dysphagia Score in identifying patients with oesophageal cancer?

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Khurram Khan ◽  
Rongkagorn Chuntamongkol ◽  
Catherine McCollum ◽  
Matthew Forshaw
Keyword(s):  
High Risk ◽  
Oesophageal Cancer ◽  
Lower Risk ◽  
Risk Group ◽  
Scoring Systems ◽  
Acid Reflux ◽  
Duration Of Symptoms ◽  
Dysphagia Score ◽  
Risk Patients ◽  
Secondary Care Setting

Abstract Aims Due to limited resources and increase in the referral for endoscopy, various scoring systems have been developed in an attempt to identify high risk patients of having oesophageal cancer. The aim of this study was to analyze the utility of Edinburgh Dysphagia Score (EDS) in patients who have presented with oesophageal cancer. Methods A retrospective cohort study of all newly diagnosed oesophageal cancers with dysphagia in a single regional MDT was performed between October 2019 and September 2020. Electronic records were interrogated and EDS calculated. EDS contained six parameters: age, sex, weight loss, duration of symptoms, localization of dysphagia and acid reflux. Patients divided into lower-risk group (EDS <3.5) and higher-risk group (EDS ≥ 3.5). Results Of the 349 patients, 182 (52.1%) had dysphagia at presentation. 149 (81.9%) were referred from the primary care. There were 127 (69.8%) male and the mean age was 69.1 ± 11.0 years. 135 (74.2%) patients had adenocarcinoma, 51 (28.0%) were T4 disease and 58 (31.9%) were metastatic. The median EDS was 7 (IQR 6-8). 178 (97.8%) patients had higher-risk EDS and 4 (2.2%) patients lower-risk EDS. Conclusions This study suggests that EDS can positively identify patients who are high risk of having oesophageal cancer in majority of patients. This simple scoring system can be used to vet the referrals in order to reduce the pressure in the secondary care setting to effectively use the available resources.

Mutation analysis of PALB2 in high-risk and lower-risk patients negative for BRCA1 and BRCA2 mutations.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 30-30
Author(s):  
Shelly Cummings ◽  
Jenny Peterson ◽  
Elisha Hughes ◽  
Rajesh R. Kaldate ◽  
Sonia Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Cancer Patients ◽  
Lower Risk ◽  
Risk Group ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Palb2 Mutation

30 Background: PALB2 has been identified as a breast cancer susceptibility gene conferring ~ 2-4 fold increased risk of breast cancer. A number of studies have estimated the PALB2 mutation prevalence to range from 0.5% - 2.9% in populations of breast cancer patients. We performed an analysis to determine the PALB2 mutation prevalence in a large U.S. referral testing population. Methods: DNA samples were anonymized from two subsets of patients: 955 early onset breast cancer patients with severe family history, and 524 patients with later onset of breast cancer and/or less severe family history. All patients were negative for deleterious sequence mutations or large rearrangements in BRCA1 and BRCA2. Results: We identified 10 disease associated PALB2 mutations in the high risk group of 955 patients and 2 deleterious PALB2 mutations in the lower risk group of 524 patients. Identified PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice site mutation. The mutation prevalence for the high risk population was 1.05% (95% C.I., 0.5 -1.92) whereas that for the lower risk population was 0.38% (95% C.I., 0.05-1.37). The observed rate of PALB2 variants of unknown significance (VUS) identified in this study was ~5% (78 VUS were in 75 of the 1479 patients that were tested). Our variant classification program which successfully decreased the VUS rate in BRCA1 and BRCA2 is similarly expected to enhance mutation classification on an on-going basis for PALB2 genetic testing. Conclusions: Genetic testing for PALB2 may be indicated as a reflex test for breast cancer patients who test negative for BRCA1 and BRCA2.

In CLL with Complex Aberrant Karyotype Distinct Entities Can Be Deciphered by Molecular Genetic and Cytogenetic Parameters

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3138-3138 ◽  
Author(s):  
Frank Dicker ◽  
Susanne Schnittger ◽  
Torsten Haferlach ◽  
Wolfgang Kern ◽  
Claudia Haferlach
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Tp53 Mutation ◽  
Risk Group ◽  
Molecular Genetic ◽  
Tp53 Gene ◽  
High Risk Group ◽  
Complex Karyotype ◽  
Tp53 Mutations ◽  
The Poor

Abstract Metaphase cytogenetics have recently defined important prognostic subgroups in CLL. In addition to the poor prognosis FISH markers del(17p) and del(11q), the presence of translocations and a complex aberrant karyotype, defined by chromosome banding analyses, have been associated with shorter overall survival in a retrospective analysis. Thus far, a complex aberrant karyotype is defined by a number of three or more chromosomal aberrations, therefore, we aimed at characterizing an unselected CLL cohort of 92 patients with complex aberrant karyotype in more detail with molecular genetic, cytogenetic, and immunophenotypic parameters. Median age at diagnosis was 62.5 years (range: 33.4–83.3 years), the male/female ratio was 2.8. An unmutated IgVH status (<= 2% mutations) was detected in 51 (60.7%) of 84 analyzed samples. A positive CD38 expression (>= 30% CD38 positive cells) was detected in 55 (64%) of 86 samples and TP53 gene mutations by denaturing high performance liquid chromatography of exons 4–9 of TP53 in 29 (36.7%) of 79 samples. As the main approach for prognostication in CLL uses FISH for del(17p), del(11q), +12, del(13q) sole and normal, we related our cohort with complex aberrant karyotype into these different FISH categories. The poor prognosis markers del(17p) and del(11q) were detected with frequencies of 39.1% (n=36) and 22.8% (n=21), respectively, accounting for almost two third of all samples (n=57, 61.9%). An overlap between del(17p) and del(11q) was detected in 5 of the 36 del(17p) cases. The intermediate risk FISH marker +12 and low risk FISH markers del(13q) as sole abnormality and “normal karyotype” appeared with an incidence of 8.7% (n=8), 21.7% (n=20) and 7.6% (n=7), respectively. The high incidence of del(11q) and del(17p) in complex karyotype seems likely, as genes implicated in sensing DNA damage and in regulating apoptosis, ATM and TP53, are candidate genes in these deleted regions. As TP53 mutations have been suggested as independent poor prognostic markers, we also added TP53 gene mutation analysis to the FISH stratification. Del(17p) was associated with TP53 mutation in 26 (86.7%) of 30 analyzed cases, whereas the three residual TP53 mutations were associated with del(11q) (n=1) and del(13q) as sole abnormality (n=2). Therefore, we chose to merge samples with high risk features within the complex karyotype into one group (n=59), i.e., samples with del(17p), del(11q) or TP53 mutation, and compared these samples to the remaining samples (n=33). Effectively, the high risk group compared to the other cohort was significantly associated with an unmutated IgVH (p=0.02, Fisher’s exact test) and with an increased, median amount of cytogenetic aberrations (4.9 vs. 3.7 aberrations, p=0.005, t-test). However, no significant difference between the two groups regarding a CD38 positive status was detected (p=0.257). The prognostic impact of high risk features (del(17p), del(11q) and TP53 mutation) within the group defined above vs the lower risk group was analyzed with log-rank statistics with respect to time from diagnosis of CLL to initial treatment (TTT). 34 patients from the high risk group and 18 patients from the low risk group were available for analysis. The high risk features within the complex karyotype were significantly associated with a higher risk of early treatment in log-rank statistics with a median TTT of 12.2 month in the higher risk group compared to 70.1 month in the lower risk group (p=0.005). In conclusion, based on poor risk cytogenetic and molecular genetic features within the group of CLL with complex aberrant karyotype, we characterized patients with a higher risk of early treatment initiation. This group includes samples with del(17p), del(11q) and TP53 mutations.

Association of CD33 Expression Level with Disease Risk-Group Classification and Induction Response In Pediatric AML: A Report From the Children's Oncology Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2732-2732
Author(s):  
Jessica A. Pollard ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Phoenix A. Ho ◽  
Rhonda Ries ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Risk ◽  
Risk Group ◽  
Group Classification ◽  
Low Risk ◽  
Intermediate Risk ◽  
Oncology Group ◽  
High Risk Disease ◽  
Pediatric Aml ◽  
Cebpa Mutations

Abstract Abstract 2732 Our previous analysis of diagnostic AML bone marrow (BM) samples from a subset of patients enrolled on Children's Oncology Group (COG) AAML03P1, a pilot study in which conventional chemotherapy was used in combination with the CD33 targeted therapeutic gemtuzumab ozogamicin (GO), demonstrated that CD33 expression is highly variable in pediatric AML and that low or absent CD33 expression was not associated with inferior clinical response. Moreover, patients with the highest CD33 expression did not have superior outcomes. Low CD33 expression was associated with low risk disease [core binding factor (CBF) AML e.g. t(8;21), inv(16) or t(16;16), CEBPA mutated AML, NPM1 mutated AML] whereas the highest CD33 expression levels were seen in patients with high-risk disease [FLT3/ITD+ disease with allelic ratio >0.4, high risk cytogenetics e.g. -7, -5, -5q]. These findings refute previous adult AML data in which CD33 expression is directly correlated with response to single agent GO and suggest, within AAML03P1, that clinical response is linked to underlying disease biology. In this larger analysis, we prospectively evaluated CD33 expression levels of AML blasts isolated from 676 pediatric diagnostic BM samples (238/340 and 438/968 patients enrolled on COG AAML03P1 and COG AAML0531 respectively) to determine whether this association persists in a larger cohort. CD33 expression, as defined by mean fluorescent intensity (MFI) of the blast population, varied over 2-log fold, and a median MFI of 128 was observed (range 3–1550.07). The study population was divided into quartiles (Q) based on CD33 expression (n= 169 patients per quartile). Median MFI was 37.49 (range 3–62) for Q1, 90 (range 62.21–128) for Q2, 171 (range 128–245) for Q3 and 349 (range 245.52–1550.07) for Q4. Samples were also screened for disease-relevant molecular mutations: 89/650 (14%) were FLT3/ITD positive; 69/587 (12%) were positive for NPM1 mutations; and 35/585 (6%) positive for CEBPA mutations. FLT3/ITD prevalence significantly increased with increasing CD33 quartile (Q1 7%, Q2 10%, Q3 17%, Q4 20%; p<0.001), whereas no definitive trend in prevalence was observed for NPM1 (Q1 7%, Q2 14%, Q3 15%, Q4 12%; p=0.158) or CEBPA mutations (Q1 6%, Q2 8%, Q3 6%, Q4 4%; p=0.307). Cytogenetic data was available for 613 (91%) samples; 177 (29%) CBF AML samples were identified and their prevalence declined with increasing quartile (Q1 51%, Q2 40%, Q3 20%, Q4 6%; p<0.001). There was no apparent association between CD33 expression and high-risk cytogenetics; however, analysis was limited by the small number of patients (9/613, 1.4%) with such mutations. For risk-group classification, complete cytogenetic and molecular data were available for 535 (79%) samples: 204/535 (38%) were classified as low-risk and 64/535 (12%) were defined as high-risk. There was an inverse association between CD33 expression and prevalence of low-risk AML (Q1 59%, Q2 50%, Q3 27%, Q4 17%; p<0.001). In contrast, the prevalence of high-risk disease increased with each quartile (Q1 5%, Q2 8%, Q3 17%, Q4 18%; p<0.001). We observed a higher median CD33 MFI with high-risk disease (median MFI 195.315; range 12–720) than with low-risk (median MFI 80.5; range 5–1550.07) or intermediate-risk (i.e., neither low- nor high-risk) disease (median MFI 163.06; range 7–1351) (p<0.001). Response from end of induction I (CR) was also determined for our patient cohort. Rates of CR were similar across CD33-expression quartiles (Q1 78%, Q2 75%, Q3 75%, Q4 72%; p=0.581). Moreover, CR rates for each risk group did not vary across quartiles (low-risk: Q1 84%, Q2 85%, Q3 88%, Q4 82%; p=0.917; intermediate-risk: Q1 77%, Q2 65%, Q3 72%, Q4 71%; p=0.594; high-risk: Q1 57%, Q2 67%, Q3 60%, Q4 72%; p=0.801). This large scale analysis supports our earlier finding that CD33 expression in pediatric AML is heterogeneous and associated with conventional risk-group criteria. As outcome data matures from COG AAML0531, the phase III counterpart of AAML03P1 in which patients are randomized to GO treatment, we will determine whether the addition of GO improves survival of patients with low versus high CD33 expression and whether this finding translates into enhanced outcomes for associated disease-risk groups. Disclosures: Franklin: Amgen : Employment, Equity Ownership.

Use of biopsy detail to identify subgroup risk in high-risk patients with prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 169-169
Author(s):  
Natasha C. Townsend ◽  
Mark K. Buyyounouski ◽  
Karen J. Ruth ◽  
Alexander Kutikov ◽  
Rosalia Viterbo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Lower Risk ◽  
Risk Group ◽  
Recursive Partitioning ◽  
Univariate Analysis ◽  
Weighted Average ◽  
Biochemical Failure ◽  
Gleason Pattern ◽  
3D Crt

169 Background: High Risk (HR) prostate cancer (CaP) patients (pts) are a heterogeneous group. A recursive partitioning analysis (RPA) was performed to determine if tissue involvement could identify patients at risk for biochemical failure (BF). Methods: Between 1992-2009, 608 HR CaP pts with complete prostate biopsy detail data (% overall tissue involvement (%TI), GP45 (weighted average of %TI for Gleason Pattern 4 or 5), Gleason Score (GS)) underwent RT with/out ADT. Primary endpoint was freedom from biochemical failure (FFBF). RPA based on time to BF was used to determine cutpoints for each prognostic variable. Multivariable (MVA) RPAs were used to assess interactions of significant variables (p<0.05) from univariate analysis (UVA). Results: Median follow up for PSA measurement was 45 months (3-193 mo). UVA RPA revealed significant cutpoints for FFBF for Tstage (higher risk of BF(HRBF) for T2c,T3b,T3c,T4,Tx vs lower risk of BF(LRBF) for T1,T2a,T2b,T3a, (p<0.001)); GS(HRBF 3+4/5, 4+5 vs LRBF 2-6, 2+3/4, 5+3/4/5 (p=0.011); iPSA (LRBF ≤37 vs HRBF >37 ng/ml (p<0.001)); dose (HRBF ≤74.9 vs LRBF >74.9 Gy); RT type(LRBF IMRT vs HRBF 3D-CRT, p=0.032), %TI (LRBF ≤53% vs HRBF >53% (p<0.001)); GP45 (LRBF ≤33% vs HRBF >33%(p<0.001)). Overall, FFBF at 5 yr was 79.2% (95%CI 75.0-82.8). For MVA RPA, splits are same as UVA unless noted. MVA RPA excluding GP45 and %TI showed 5 groups (5 yr FFBF 45.9%, 66.8%, 74.2%, 84.2% and 89.5%; N 16, 195, 69, 20 and 308, respectively). Tstage, iPSA, GS and RT type had significant interactions, with highest risk group including PSA >44ng/ml, low Tstage and 3D-CRT, and lowest risk group including PSA ≤44 ng/ml, lower risk Tstage, and lower risk GS. Including %TI in the RPA, significant interactions were between %TI (2 splits), iPSA and GS (5 yr FFBF 50.0%, 62.5%, 71.9%, 80.4% and 92.7%; N 80, 24, 65, 233, and 206, respectively). Highest risk group included pts with %TI >53%; lowest risk included pts with %TI <17%, iPSA <40 ng/mL, and GS lower risk. Using GP45 instead of %TI, 3 groups were found: high GP45; low GP45 and iPSA ≥40; low GP45 and iPSA<40 ng/ml, (5 yr FFBF 58.9%, 67.7% and 85.5%; N 103, 63 and 442, respectively). Conclusions: Pts with > 53% TI, > 33% GP45 and iPSA > 40 ng/ml are at highest risk of failure, and should be considered for most aggressive treatment.

scholarly journals The Impact of Comorbidities on Clinical Outcome of Patients with Myelodysplastic Syndromes: A Real-Life Survey

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4668-4668
Author(s):  
Enrico Balleari ◽  
Chiara Salvetti ◽  
Andrea Bacigalupo ◽  
Gianluca Forni ◽  
Marco Gobbi ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Lower Risk ◽  
Risk Group ◽  
Real Life ◽  
High Risk Group ◽  
Low Risk ◽  
Survival Analyses ◽  
Intermediate Group ◽  
Comorbidity Index

Abstract Introduction: Myelodysplastic syndromes (MDS) are a highly heterogeneous group of clonal disorders, with very different prognosis in given individuals, overall survival (OS) ranging from more than 10 years (y) for the more indolent conditions to only few months (m) for the forms approaching AML; beside of the well-established disease-related prognostic systems (classical IPSS or its revised form [IPSS-R], the prognostic implication of comorbidities is emerging as a relevant patient-related factor influencing clinical outcome. Aim of our study was to evaluate the clinical impact of comorbidities in a series of MDS patients whatever treated in a “real-life” setting. Methods: this retrospective cohort study involved the MDS patients consecutively registered between Jan 2011 and Dec 2013 into the Registro Ligure delle Mielodisplasie database, a regional registry established within the framework of the Italian Network of regional MDS registries. Data of 318 patients (pts) with available complete assessment of comorbidities at diagnosis were included into the study. The clinical characteristics and comorbidities were all considered into the analysis. Comorbidities were evaluated according to both hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and MDS-specific comorbidity index (MDS-CI). All survival analyses were made from the date of diagnosis to last follow-up, death, or progression to AML. Unless specified, survival analyses were Cox models using continuous variables accounting for interactions. Results: Our cohort mainly consisted of older (median age 75y (range 40-98) “lower-risk” MDS pts: according to IPSS stratification, 151 (54.7%) pts were classified as low-risk, 86 (31.2%) as intermediate-1, 32 (11.6%) as intermediate-2 and 7 (2.5%) were in the high-risk group. One or more comorbidity of any grade of severity was seen in 177 (55.7%) pts at diagnosis. The more common comorbidity was cardiac (26.5%). At least a single comorbidity was present in 61.2% of pts older than 75y and in 50.6% of younger pts (p=0.07). Cardiovascular disorders were more frequent among older (32.9% for >75y vs 15.1% for ≤ 75y, p<0.001), and among males (28.7% vs 17.1% for females, p=0.02). According to HCT-CI risk stratification, 141pts (44.3%) were in the low-risk group, 94 (29.6%) in the intermediate-risk group, and 83 (26.1%) in the high-risk group, while according to MDS-CI, 197 (61.9%) pts had a low-risk score, 99 (31.1%) were intermediate, and 22 (6.9%) were in the high-risk group. MDS-CI score was higher among males (43.8% vs 30.7% for females, p=0.02). It was also higher among subjects >75 y (48% vs. 28.9% for < 75 y (p=0.001). A lower comorbidity score impacted on the clinical choice for active forms of therapy, while pts with an higher burden of comorbidities were preferentially treated with supportive care, even if difference did not reach significance (p=0.07). Overall survival and risk of non-leukemic death (NLD) were analyzed (median f.u. 26.9 m (range 1-220). HCT-CI did not significantly correlated with OS nor NLD (p= 0.1 and p= 0.07, respectively), while MDS-CI was found to be of prognostic significance both for OS (mean 136.6 (95%CI 116-157) m for the low-risk group, 81.3 (95%CI 61-102) m for the intermediate group and 48.1 (95%CI 30-66) m for the high-risk group, p=0.001) and for NLD (mean 159.6 (95%CI 139-180) m for the low-risk group, 96.5 (95%CI 72-121) m for the intermediate group and 49 (95%CI 31-67) m for the high-risk group (p<0.001). The correlation was significant (p<0.001) in IPSS or IPSS-R “lower-risk” (low and intermediate-1 risk or very-low, low and intermediate groups, respectively) but not in IPSS nor IPSS-R “higher-risk” (intermediate-2 and high or high and very-high groups, respectively) pts. In multivariate analysis, the prognostic impact of MDS-CI remained independent of baseline IPSS (p=0.01) or IPSS-R (p=0.03). Conclusions: a comprehensive evaluation of comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporate to current prognostic scores in order to better define clinical management of these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals P-OGC67 Gastric GISTs: Can presentation, Location and Radiological Features predict behaviour? – Experience in a UK cohort

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Hannah Gerretsen ◽  
Gincy George ◽  
Beth Russell ◽  
James Gossage ◽  
Mark Kelly ◽  
...  
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Risk Group ◽  
Risk Groups ◽  
Endoscopic Biopsy ◽  
Low Risk ◽  
Cross Sectional ◽  
Gastric Gists ◽  
Tertiary Centre ◽  
Histological Confirmation

Abstract Background Gastrointestinal stromal tumours (GISTs) most commonly arise in the stomach, vary significantly in behaviour and can be difficult to risk stratify accurately pre-operatively. They are increasingly being identified incidentally during endoscopies or cross-sectional imaging. They have malignant potential and but vary from very low to high-risk. Pre-operatively, histological diagnosis can be achieved by performing endoscopic ultrasound (EUS) guided fine-needle aspirate or biopsy, but samples often contain insufficient material. This study aims to assess other features help identify aggressiveness of GISTs pre-operatively to help guide management decisions. Methods This is a retrospective cohort study analysing patients treated surgically for GIST from 2011-2020 at a UK tertiary centre. Exclusion criteria were non-gastric GISTs and patients who received a different diagnosis post-operatively. Hospital electronic patient record and e-noting systems were used to collect data. Risk groups were stratified according to the NCCN risk classification for GIST. ‘Very low risk’ and ‘low risk’ groups were combined in the analysis to form the ‘lower risk’ group; ‘moderate risk’ and ‘high risk’ categories combined to form the ‘higher risk’ group. Statistical analyses were conducted using STATA version 15. Results 171 patients were included in total. OGD diagnosed gist on histology if ulcerated in 14.7% of cases. EUS biopsy was performed in 39% of cases pre-operatively – 84.6% of these were diagnostic. There was a higher proportion of higher risk GISTs in the GOJ/cardia region than lower risk GISTs (16.2% versus 6.7%), though this did not reach statistically significance (p = 0.32). A greater proportion of higher risk tumours were irregular in outline (p=.26),  heterogenous (p = 0.003) and necrotic (p = 0.001) than lower risk tumours. In addition, higher risk tumours were significantly more likely to be exophytic than lower risk tumours, which were significantly more endophytic (p = 0.05). A ROC curve including all the variables had an AUC of 0.8971. Conclusions This is the largest analysis of gastric GISTs in a UK population. This study found that a higher proportion of higher risk tumours were irregular, heterogenous and necrotic than lower risk tumours. In this study, a greater proportion of higher risk tumours arose in the GOJ/cardia. In keeping with muscularis origin, endoscopic biopsy was found to be a poor diagnostic tool unless ulcerated. EUS and FNA biopsies had a much higher rate of histological confirmation. This knowledge might help facilitate a more individualised approach with non-operative surveillance in lower risk tumours or expedited surgery in higher risk lesions.

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