scholarly journals Genetic Profiling Augments Prognostic Value of the EUTOS Long-Term Survival Score for Disease-Specific Mortality in Imatinib-Treated Asian Chronic Myeloid Leukaemia Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3077-3077 ◽  
Author(s):  
Hein Than ◽  
Weng Kit Lye ◽  
Chiu Hong Seow ◽  
Colin Nicholas Sng ◽  
John Carson Allen ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Deletion Polymorphism ◽  
Term Survival ◽  
Long Term Survival ◽  
Genetic Profiling

Abstract Introduction: Long-term survival rates among patients with chronic-phase chronic myeloid leukaemia (CP-CML) have remarkably improved since the introduction of imatinib, a BCR-ABL1 tyrosine-kinase inhibitor (TKI), as the standard first-line therapy. Several prognostic scores have been employed to predict clinical response and survival of CP-CML patients treated with TKIs. The EUTOS long-term survival (ELTS) score was recently introduced and shown to predict the probability of CML-specific death in long-term surviving patients on imatinib therapy, more effectively than the existing scores. The ELTS score was calculated by a formula that included age at diagnosis, spleen size below costal margin, platelet count and blast percentage in peripheral blood as prognostic factors. In our study, we evaluated the ELTS score in predicting the probabilities of CML-specific death, long-term overall survival (OS) and progression-free survival (PFS) rates in Asian CML patients treated with imatinib. As genetic differences, particularly the BCL-2 like 11 (BIM) deletion polymorphism, have been shown to confer intrinsic resistance to imatinib in East-Asian patients, we also explored the role of BIM deletion polymorphism profiling as a prognostic biomarker for CML-specific death among different risk groups stratified by the ELTS score. Methods: A retrospective analysis was performed on CP-CML patients treated with first-line imatinib within one year of diagnosis in Singapore General Hospital from June 2001 to November 2014. The ELTS score was obtained with online calculator at www.leukemia-net.org. Low-risk group was defined as a score ≤1.568, intermediate-risk group as a score >1.568 but ≤2.2185, and high-risk group as a score >2.2185. Progression was defined as transformation to accelerated or blast phase or death from any cause. OS and PFS were calculated with the Kaplan-Meier method and compared by the log-rank test. Cumulative incidence probabilities of CML-specific death were compared by the Gray test. Findings: 134 patients were included for analysis. 63% were Chinese, 17% were Malays, 8% were Indians and 12% were of mixed ethnic origin. Median age at diagnosis was 45 years and 60% were male. Median follow-up was 7.7 years (range: 0.4 to 13.2 years). 17 deaths out of 134 patients (13%) were recorded, of which 11 were CML-specific (65%). 54% of patients were categorised as low-risk, 36% as intermediate-risk and 10% as high-risk by the ELTS score. The cumulative incidence probabilities of CML-specific death at 10 years were 43% in high-risk (hazard ratio (HR): 11.76, 95% confidence interval (CI): (2.32, 59.71), p=0.003) and 9% in intermediate-risk (HR: 2.24, 95% CI: (0.37, 13.49), p=0.38) compared to 3% in low-risk groups.10-year OS probabilities were 50%, 82% and 93% in high-, intermediate- and low-risk ELTS groups respectively (p=0.001). 10-year PFS probabilities were 50%, 84% and 89% in high-, intermediate- and low-risk ELTS groups respectively (p=0.004). Among 103 East-Asian patients with low- and intermediate-risk ELTS sub-groups, 15% harboured BIM deletion polymorphism. The probability of CML-specific death at 10 years in this subset was 16% with BIM deletion polymorphism, but 4% without polymorphism (HR 4.30, 95% CI: (0.76, 24.35), p=0.099). 10-year OS probabilities in the subset were 75% and 89% in patients with and without BIM deletion polymorphism respectively (p=0.014). Conclusions: The ELTS score was able to predict the probability of CML-specific death and identify high-risk patients in our multi-racial Asian CML patients treated with imatinib. Genetic profiling using BIM deletion polymorphism provided further stratification by identifying a subset of inferior long-term survivors with high probability of CML-specific death among otherwise non high-risk patients. Disclosures Chuah: Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Chiltern: Honoraria.

scholarly journals The Impact of Surgery on Long-Term Survival of Patients with Primary Gastric Diffuse Large B-Cell Lymphoma: A SEER Population-Based Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ju-Li Lin ◽  
Jian-Xian Lin ◽  
Ping Li ◽  
Jian-Wei Xie ◽  
Jia-bin Wang ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Intermediate Risk ◽  
Term Survival ◽  
Long Term Survival ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

Background. The aim of this retrospective study was to compare the long-term survival of patients receiving conservative with surgical treatment to analyze the prognostic factors and the impact of surgery on oncological outcomes of patients with primary gastric diffuse large B-cell lymphoma. Methods. A total of 2647 patients diagnosed with primary gastric diffuse large B-cell lymphoma from 1998 to 2014 were extracted from SEER database. Propensity matching was performed to compare the clinicopathological characteristics of the two groups. Based on the recursive partitioning analysis, the patients were divided into three risk subgroups: low risk, intermediate risk, and high risk. Results. After propensity score matching, patient characteristics did not differ significantly between the two groups. The 5-year cancer-specific survival rates of the surgical group and the conservative treatment group were, respectively, 60% and 59.2% (P=0.952) before propensity matching and 64.2% and 58.6% (P=0.046) after propensity matching. According to the multivariate analysis, age, tumor stage, and chemotherapy and surgery were independent risk factors for long-term survival. The 5-year cancer-specific survival rates differed significantly between the low-risk, intermediate-risk, and high-risk patients (76.2% vs. 57.4% vs. 25.5%, respectively, P<0.001). The 5-year cancer-specific survival rate of the surgical group was significantly higher than that of the conservative treatment group in the low-risk patients. However, it did not differ significantly in the intermediate-risk and high-risk patients (P>0.05). Conclusions. A prognostic model was constructed based on the independent risk factors of age, tumor stage, and chemotherapy. The prognostic model indicated that low-risk patients (age<75 years, stage I/II, with/without chemotherapy) undergoing surgical treatment may benefit from long-term survival, while intermediate- and high-risk patients (age≥75 years, stage I/II, with/without chemotherapy or III/IV patients, with/without chemotherapy) gain no significant benefit from surgery.

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 A novel hyperinflammation clinical risk tool, HI5-NEWS2, predicts mortality following early dexamethasone use in an observational cohort of hospitalised COVID-19 patients.

2021 ◽  
Author(s):  
Michael R Ardern-Jones ◽  
Hang T.T. Phan ◽  
Florina Borca ◽  
Matthew Stammers ◽  
James Batchelor ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Dexamethasone Treatment ◽  
Dexamethasone Therapy ◽  
Risk Patients ◽  
Anti Inflammatory

Background The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. Methods Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. Findings Of 1265 patients, high risk of HI (high HI5-NEWS2) (n=367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n= 455, 36.0%). An intermediate risk group (n= 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p=0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p=0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p=0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p =0.31). Interpretation The HI5-NEWS2 measured at COVID-19 diagnosis, strongly predicts mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention. Funding No external funding.

scholarly journals The Impact of EUTOS Long-Term Survival (ELTS) Score on Predicting Progression and Survival Among Turkish Patients with Chronic Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4600-4600
Author(s):  
Mert Bektaş ◽  
Tuğrul Elverdi ◽  
Ayşe Salihoğlu ◽  
Muhlis Cem Ar ◽  
Şeniz Öngören ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Roc Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Term Survival ◽  
Hazard Ratios ◽  
Sokal Score

Abstract Introduction and Objectives: For patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP), four baseline prognostic scores are commonly used including the Sokal score and the most recently introduced EUTOS long-term survival (ELTS) score. The ELTS score was shown to be superior to the Sokal score for predicting survival. The aim of the study is to evaluate the value of ELTS score on predicting disease progression and survival in Turkish pts with CML-CP. Material and Method: Demographic, laboratory and clinical features, disease responses to tyrosine kinase inhibitor (TKI) therapy and survival of CML-CP pts, who received upfront imatinib (IM) between 2003 and 2018 were analyzed retrospectively. Treatment responses were reevaluated according to European LeukemiaNet 2013 recommendations. Risk groups analysis, discrimination and hazard ratios (HRs) were evaluated with Cox regression and Kaplan-Meier survival analysis. Receiver operating characteristic (ROC) analysis was performed to examine the effects of scores on predicting overall survival (OS) and progression-free survival (PFS). Results: A total of 185 pts were included, of which 103 (55.7%) were male and median age was 47 years (range, 16 - 81 years) (Table 1). The percentages of pts with low-, intermediate-, and high-risk ELTS scores were 60.5%, 25.9%, and 13.5%, respectively. For the Sokal score, these percentages were 37.3%, 40.5%, and 22.2% respectively. For Sokal high-risk pts, only 46.3% were classified as high-risk according to the ELTS score. Similarly, 44% of pts with intermediate Sokal risk had low-risk ELTS score (Fig. 1). Seventy-seven pts (41.6%) had at least one comorbidity, and the most common comorbidities were hypertension (21.6%), diabetes mellitus (13%), and ischemic heart disease (12.4%) (Table 1). The median durations of IM therapy and follow-up were 2728 (range, 14 - 6320 days) and 3473 (range, 71 - 6320 days) days, respectively. Complete hematologic and early molecular (BCR-ABL1 IS &lt;10% at 3 months) responses at 3 months were 95.6% and 75.9%, respectively. Complete cytogenetic and major molecular response rates at 6 and 12 months were 72.3% and 86.1% and 45.4% and 54%, respectively. Thirty-five pts (18.9%) switched to second-generation TKI therapy and 6 pts (3.2%) progressed to advanced-phase disease during the follow-up (Table 1). For PFS, with reference to the low-risk Sokal score, the HR of high-risk groups was 9.301 (95% CI: 1.086-79.656, p=0.042) (Fig. 2A). Similarly, with reference to the low-risk ELTS score, the HR of intermediate- and high-risk groups were 4.744 (95% CI: 0.43-52.314, p=0.204) and 14.642 (95% CI: 1.523-140.791, p=0.020) (Fig. 2B). Regarding OS, with reference to the low-risk Sokal score, the HR of the intermediate- and high-risk groups were 1.835 (95% CI: 0.564-5.964, p=0.313) and 6.412 (95% CI: 2.11-19.489, p=0.001), respectively (Fig. 2C). With reference to the low-risk ELTS score, the HR of the intermediate- and high-risk groups were, 3.263 (95% CI: 1.242-8.576, p=0.016) and 7.258 (95% CI: 2.762-19.074, p&lt;0.001) respectively (Fig. 2D). In the ROC analysis, the ELTS score was superior than the Sokal risk score for both predicting PFS (AUC=0.820 vs. AUC=0.818) and OS (AUC=0.762 vs. AUC=0.744). During the follow-up, 27 (14.6%) pts died, of which 6 died due to CML progression and causes of death were unrelated to CML in 21. Conclusion: In our study, we showed that the ELTS score could successfully predict high-risk pts compatible with the literature. With higher hazard ratios and better risk group stratifications, the ELTS score outperformed the Sokal score. The ELTS score can help clinicians to better discriminate poor prognostic pts and can promote optimal treatment strategies for these pts with potentially worse prognosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-term safety of growth hormone treatment in childhood: Two large observational studies NordiNet ® IOS and ANSWER

2021 ◽  
Author(s):  
Lars Sävendahl ◽  
Michel Polak ◽  
Philippe Backeljauw ◽  
Joanne C Blair ◽  
Bradley S Miller ◽  
...  
Keyword(s):  
High Risk ◽  
Mortality Risk ◽  
Observational Studies ◽  
Risk Group ◽  
Risk Groups ◽  
Incidence Rates ◽  
Low Risk ◽  
Risk Category ◽  
Gh Treatment

Abstract Context GH treatment has a generally good safety profile; however, concerns of increased mortality risk in adulthood have been raised. Objective Assessing the long-term safety of GH treatment in clinical practice. Design Two multicenter longitudinal observational studies: NordiNet® International Outcome Study (2006–2016, Europe) and ANSWER Program (2002–2016, USA). Setting Data collected from 676 clinics. Patients Pediatric patients treated with GH, classified into three risk groups based on diagnosis. Intervention Daily GH treatment. Main Outcome Measures Incidence rates (events/1000 patient-years) of adverse drug reactions (ADRs), serious adverse events (SAEs), and serious ADRs, and their relationship to the GH dose. Results The combined studies comprised 37,702 patients (68.4% in low-risk, 27.5% in intermediate-risk, and 4.1% in high-risk groups) and 130,476 patient-years of exposure. The low-risk group included children born small for gestational age (SGA; 20.7%) and non-SGA children (e.g. with GH deficiency; 79.3%). Average GH dose up to the first adverse event (AE) decreased with increasing risk category. Patients without AEs received higher average GH doses than patients with &gt;1 AE across all groups. A significant inverse relationship with GH dose was shown for ADR and SAE incidence rates in the low-risk group (P = 0.0029 and P = 0.0003, respectively) and the non-SGA subgroup (P = 0.0022 and P = 0.0015, respectively), and for SAEs in the intermediate- and high-risk groups (P = 0.0017 and P = 0.0480, respectively). Conclusions We observed no indication of increased mortality risk nor AE incidence related to GH dose in any risk group.

scholarly journals 55例血管免疫母细胞性T细胞淋巴瘤的临床特征和预后模型

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-38
Author(s):  
Xiaohong Tan ◽  
Jie Sun ◽  
Sha He ◽  
Chao Rong ◽  
Hong Cen
Keyword(s):  
High Risk ◽  
Prognostic Model ◽  
Risk Group ◽  
Prognostic Index ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Ecog Ps ◽  
Medical University

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct subtype of peripheral T-cell lymphoma with unique clinical and pathological features. This study aim to analyze the characteristics of AITL and to design a prognostic model specifically for AITL, providing risk stratification in affected patients. We retrospectively analyzed 55 newly diagnosed AITL patients at the Affiliated Tumor Hospital of Guangxi Medical University from January 2007 to June 2016 and was permitted by the Ethics Committee of the Affiliated Tumor Hospital of Guangxi Medical University. Among these patients, the median age at diagnosis was 61 (27-85) and 54.55% (30/55) of the patients were older than 60 years. 43 patients were male, accounting for 78.18% of the whole. Among these, 92.73% (51/55) of the diagnoses were estimated at advanced stage. A total of 20 (36.36%) patients were scored &gt;1 by the ECOG performance status. Systemic B symptoms were described in 16 (29.09%) patients. In nearly half of the patients (27/55; 49.09%) had extranodal involved sites. The most common extranodal site involved was BM (11/55; 20.00%). 38.18% (21/55) and 27.27% (15/55) patients had fever with body temperature ≥37.4℃ and pneumonia, respectively. 40% (22/55) patients had cavity effusion or edema. Laboratory investigations showed the presence of anemia (hemoglobin &lt;120 g/L) in 60% (33/55), thrombocytopenia (platelet counts &lt;150×109/L) in 29.09% (16/55), and elevated serum LDH level in 85.45% (47/55) of patients. Serum C-reactive protein and β2-microglobulin levels were found to be elevated in 60.98% (25/41) and 75.00% (36/48)of the patients, respectively. All patients had complete information for stratification into 4 risk subgroups by IPI score, in which scores of 0-1 point were low risk (9/55;16.36%), two points were low-intermediate risk (17/55; 30.92%), three points were high-intermediate risk (20/55; 36.36%), and four to five points were high risk (9/55; 16.36%). 55 patients were stratified by PIT score with 7.27% (4/55) of patients classified as low risk, 32.73% (18/55) as low-intermediate risk, 34.55% (19/55) as high-intermediate risk, and 25.45% (14/55) as high risk depending on the numbers of adverse prognostic factors.The estimated two-year and five-year overall survival (OS) rate for all patients were 50.50% and 21.70%. Univariate analysis suggested that ECOG PS (p= 0.000), Systemic B symptoms (p= 0.006), fever with body temperature ≥ 37.4℃ (p= 0.000), pneumonia (p= 0.001), cavity effusion or edema (p= 0.000), anemia (p= 0.013), and serum LDH (p= 0.007) might be prognostic factors (p&lt; 0.05) for OS. Multivariate analysis found prognostic factors for OS were ECOG PS (p= 0.026), pneumonia (p= 0.045), and cavity effusion or edema(p= 0.003). We categorized three risk groups: low-risk group, no adverse factor; intermediate-risk group, one factor; and high-risk group, two or three factors. Five-year OS was 41.8% for low-risk group, 15.2% for intermediate-risk group, and 0.0% for high-risk group (p&lt; 0.000). Patients with AITL had a poor outcome. This novel prognostic model balanced the distribution of patients into different risk groups with better predictive discrimination as compared to the International Prognostic Index and Prognostic Index for PTCL. Disclosures No relevant conflicts of interest to declare.

Induction Therapy with “3+7” Chemotherapy Plus ATRA Followed by Consolidations with Three Courses of Idarubicin Alone and Maintenance Therapy with ATRA in Newly Diagnosed Acute Promyelocytic Leukemia (APL) Has An Excellent Leukemia-Free Survival but Minimal Toxicity in Low and Intermediate Risk Groups.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2072-2072
Author(s):  
Moon-Young Choi ◽  
Yeung-Chul Mun ◽  
Se Hoon Park ◽  
Eun Kyung Cho ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Relapse Rate ◽  
Induction Therapy ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Newly Diagnosed

Abstract Abstract 2072 Poster Board II-49 Backgrounds Currently, there are many efforts to design risk-adapted strategies in newly diagnosed acute promyelocytic leukemia (APL) by modulating treatment intensity and those seem to be an efficient approach to minimize treatment-related morbidity and mortality (TRM) while maintain the potential in cure for each relapse-risk group. We had postulated that maintaining of Ara-C during induction therapy might have acceptable toxicities yet obtaining good CR in newly diagnosed APL, and idarubicin alone during consolidation periods might have excellent LFS and OS with low relapse rate. Patients and Methods Eighty six patients with newly diagnosed APL were enrolled in the “multicenter AML-2000 trial” after informed consents were obtained during the period of January 2000 to July 2007. For remission induction therapy, patients received oral ATRA (45mg/m2/d, maintained until CR) combined with idarubicin (12mg/m2/d, D1-D3) plus Ara-C (100mg/m2/d, D1-D7). After CR achievement, patients received 3 monthly consolidation courses consisting of idarubicin (12mg/m2/d, D1-D3) alone and maintenance therapy with ATRA (45mg/m2/d, D1-D15, every 2 month) alone had continued for 2 years. Total patients were divided into low-risk, intermediate-risk and high-risk groups according to a predictive model for relapse risk (Sanz score) based on pretreatment WBC and platelet count and the treatment outcomes were compared in the different risk groups. Results The median age of our cohort was 40 years old (range; 6-80) and median follow-up was 27 months (range; 1-90). The distribution of patients in the 3 risk groups was as follows ; 28 (32.6%) patients in low-risk, 40 (46.5%) in intermediate-risk and 18 (20.9%) in high-risk. Overall, CR was achieved in 78 (90.7%) of 86 patients. The CR rate according risk groups was 96.4% in low-risk, 87.5% in intermediate-risk, and 88.9% in high-risk group and there was no significant statistical difference among the different risk groups. During induction therapy, 48 (55.8%) patients experienced grade 3-4 treatment-related toxicity (TRT), mostly fever and infection (38.8% of all patients) and 6 (7.0%) patients died of treatment-related complications. During 3 consolidation courses, 25 (29.1%) of 78 patients experienced grade 3-4 TRT in 1st course, 27 (36.0%) of 75 patients in 2nd course, and 14 (28.0%) of 50 patients in 3rd course. Overall, 3 (3.5%) patients died of treatment-related complications in CR. The incidence of TRT and treatment-related mortality (TRM) during induction or consolidation therapy showed no significant statistical difference among the different risk groups. The relapse occurred in 6 (7.0%) patients; 2 cases in intermediate-risk and 4 cases in high-risk. However, none had relapsed in low risk group, 5 patients of relapsed patients relapsed during consolidation courses and only one patient, however, relapsed during maintenance therapy. The overall survival (OS) and leukemia-free survival (LFS) rate at 7 years in all of patients was 76.7% and 83.5%, respectively. The OS rate at 7 years was 92.9% in low-risk, 78.6% in intermediate-risk and 53.6% in high-risk group (P:0.04) and the LFS rate at 7 years was 96.4%, 83.4% and 62.2% respectively, showing the significant difference between 3 different risk groups (P:0.046). Conclusions This study indicates that our protocol composed of induction therapy with “3+7” chemotherapy plus ATRA followed by consolidations with three courses of idarubicin alone and maintenance therapy with ATRA alone yields a high CR rate and low relapse rate but minimal acceptable toxicities. Despite of adding Ara-C during induction therapy, we did not find much significant toxicities but having good CR rates, and despite of not adding any additional low/intermediate dose chemotherapies(ie, 6MP), we were able to observe significantly high relapse rate in low and intermediate risk group with excellent LFS and OS. Meanwhile, in high-risk group, the relapse rate was significantly higher than other risk groups and most of the relapses occurred in the middle of consolidation courses. This data suggests that our consolidation therapy composed of anthracycline alone may be not enough to minimize risk of relapse in high-risk group in contrast with the low and intermediate-risk groups. More intensive consolidation therapy combined with other effective, but get tolerable chemotherapies or hematopoietic stem cell transplantation in first CR or the combination of arsenic trioxide or others in front-line therapy should be considered in the patients with high-risk of relapse. Disclosures: No relevant conflicts of interest to declare.

The EUTOS Survival Score Is Preferable over the Sokal Score for Prognosis of Long-Term Survival of Patients with Chronic Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 595-595 ◽  
Author(s):  
Markus Pfirrmann ◽  
Joerg Hasford ◽  
Susanne Saussele ◽  
Anna Turkina ◽  
Witold Prejzner ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Chronic Phase ◽  
Low Risk ◽  
Term Survival ◽  
Survival Score ◽  
Risk Patients ◽  
Sokal Score

Abstract Introduction: The in-study and out-study sections of the European Treatment and Outcome Study (EUTOS) registry comprise data on imatinib-treated adult patients with chronic myeloid leukemia (CML) who were prospectively enrolled in clinical studies or registries between 2002 and 2006. All patients diagnosed with chronic-phase Philadelphia chromosome-positive CML were eligible for analysis. The new EUTOS long-term survival (ELTS) score was developed in 2,205 in-study patients (Blood 2014; 124(21):153). Its purpose is the discrimination of three risk groups with clinically significantly different probabilities of dying from CML. The score was validated in 1,120 out-study patients. Aims: Up to now, many investigators still apply the Sokal score for the prognostic discrimination of CML-patients treated with tyrosine kinase inhibitors (TKIs). The Sokal score allocated more than 20% of chronic-phase patients to the high-risk group while it was 12% with the new ELTS score. Long-term outcome with tyrosine kinase inhibitors (TKIs) suggests that the allocation of more than 20% chronic-phase CML patients into a high-risk group is too pessimistic. The focus of this analysis was the comparison of risk group allocations and prognosis between the two scores. Methods: Survival time was calculated from the date of start of treatment to death or to the latest follow-up date. Survival was censored at the time of allogeneic stem cell transplantation in first chronic phase. Cumulative incidence probabilities (CIPs) of dying of CML were compared with the Gray test and overall survival probabilities with the log-rank test. As "death due to CML", only death after confirmed disease progression was regarded. Progression was defined in accordance with the recommendations of the ELN (Baccarani et al, Blood 2013). Level of significance was 0.05. Results: Both registries combined, the 3,325 patients had a median observation time of 6.1 years. Six-year overall survival probability was 91% (95% confidence interval (CI): 89-92%). Death was due to CML in 142 of 309 deceased patients (46%).The 6-year CIP of dying of CML was 4% (CI: 4-5%). From low to high risk groups, the Sokal score resulted in 6-year CIPs of 3% (n=1358 (41%), CI: 2-4%), 4% (n=1209 (36%), CI: 3-5%), and 8% (n=758 (23%), CI: 6-11%) and the ELTS score in 6-year CIPs of 2% (n=2030 (61%), CI: 2-3%), 6% (n=898 (27%), CI: 4-7%), and 13% (n=397 (12%), CI: 10-17%). Of the 758 patients allocated to high risk by the Sokal score, the ELTS score classified 165 (22%) as low risk and 265 (35%) as intermediate risk. Compared to the 328 high-risk patients (43%) according to both scores (6-year CIP of dying: 13%, CI: 9-17%), the CIPs of dying were significantly lower for the 165 low-risk patients (p=0.0062, 6-year CIP: 5%, CI: 2-9%) and for the 265 intermediate-risk patients (p=0.0050, 6-year CIP: 5%, CI: 3-9%). These 430 Sokal high but ELTS non-high-risk patients (6-year OS: 89%. CI: 86-92%) showed significantly higher OS probabilities than the 328 Sokal and ELTS high-risk patients (p=0.030, 6-year OS: 81%. CI: 76-85%). Of the 2030 patients identified as low risk by the ELTS score, the Sokal score allocated 603 (30%) to the intermediate- and 165 (8%) to the high-risk group. Without significant CIP differences to the latter group, at 6 years, the CIP of dying was 2% (CI: 1-3%) in the 1262 low-risk and also 2% in the 603 intermediate-risk patients (CI: 1-3%). The OS probabilities of the 768 non-low-risk patients according to the Sokal score (6-year OS: 93%. CI: 91-95%) were not significantly different from the 1262 classified as low-risk by both scores (6-year OS: 95%. CI: 93-96%). Conclusions: To be able to perform comparisons between the various prognostic groups suggested by the Sokal and the EUTOS survival score with a reasonable power, data of in- and out-study samples were combined. The Sokal score allocated an absolute difference of 12% (n=430) more patients to the high-risk groups than the EUTOS survival score. As these patients had significantly and clinically relevantly lower CIPs and higher OS probabilities, the allocation of the Sokal score was not appropriate. Contrarily, the long-term outcome of 768 patients assessed as low-risk by the ELTS and non-low-risk by the Sokal score was not different from the outcome of 1262 assesses as low-risk patients by both scores. For prognosis of long-term survival outcome, the use of the EUTOS survival score is recommended. Disclosures Pfirrmann: BMS: Consultancy, Honoraria; Novartis Pharma: Consultancy, Honoraria. Hasford:Novartis: Research Funding. Saussele:Novartis Pharma: Honoraria, Other: Travel grant, Research Funding; BMS: Honoraria, Other: Travel grant, Research Funding; ARIAD: Honoraria; Pfizer: Honoraria, Other: Travel grant. Turkina:Bristol Myers Squibb: Consultancy; Pfizer: Consultancy; Novartis Pharma: Consultancy. Prejzner:Novartis Pharma: Honoraria; BMS: Honoraria. Steegmann:Novartis Pharma: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Simonsson:Novartis Pharma: Research Funding. Zaritskey:University of Heidelberg: Research Funding; Novartis: Consultancy. Zackova:Novartis Pharma: Consultancy; Bristol Myers Squibb: Consultancy. Janssen:Novartis: Research Funding; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; ARIAD: Consultancy. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Hehlmann:Novartis Pharma: Research Funding; BMS: Consultancy. Baccarani:Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Speakers Bureau.

scholarly journals Integrated Multiparametric Radiomics and Informatics System for Characterizing Breast Tumor Characteristics with the OncotypeDX Gene Assay

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2772
Author(s):  
Michael A. Jacobs ◽  
Christopher B. Umbricht ◽  
Vishwa S. Parekh ◽  
Riham H. El Khouli ◽  
Leslie Cope ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Group ◽  
Area Under The Curve ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Breast Cancer Patients ◽  
Gene Assay

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained using the mpMRI, clinical, pathologic, and radiomic descriptors for prediction of the OncotypeDX risk score. The trained mpRad IRIS model had a 95% and specificity was 83% with an Area Under the Curve (AUC) of 0.89 for classifying low risk patients from the intermediate and high-risk groups. The lesion size was larger for the high-risk group (2.9 ± 1.7 mm) and lower for both low risk (1.9 ± 1.3 mm) and intermediate risk (1.7 ± 1.4 mm) groups. The lesion apparent diffusion coefficient (ADC) map values for high- and intermediate-risk groups were significantly (p < 0.05) lower than the low-risk group (1.14 vs. 1.49 × 10−3 mm2/s). These initial studies provide deeper insight into the clinical, pathological, quantitative imaging, and radiomic features, and provide the foundation to relate these features to the assessment of treatment response for improved personalized medicine.

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