The FLIPI2 SCORE Predicts PROGRESSION-FREE SURVIVAL (PFS) and OVERALL SURVIVAL (OS) IN AN INDEPENDENT SERIES of Follicular LYMPHOMA: A Single Institution EXPERIENCE

Abstract Abstract 3128 Background: follicular lymphoma is an incurable, long-lasting disease with an heterogeneous outcome. Several prognostic systems have been proposed, and recently a new one, the FLIPI2 score based on five parameters has been published. However, in order to confirm its prognostic utility, further studies at other centers are highly recommendable. Aim: to validate the new FLIPI2 score in independent series of follicular lymphoma patients diagnosed at our institution between February 1990 and July 2010. Patients and methods. We considered 180 patients consecutively diagnosed with follicular diagnosis in the period described and from whom all variables required were available. The variables included were: beta2microglobulin higher than the upper normal value, longest diameter of the largest involved node longer than 6 cm, bone marrow infiltration, hemoglobin level lower than 120 g/L and age older than 60 years (one point if present). Three risk groups were identified: low risk (0 points), intermediate risk (1 -2) and high risk (3 or more) Progression-free survival was measured from date of treatment until date of progression or death from any cause. Continuous variables were summarized as median and range, categorical variables reported as counts, and PFS and OS carried out using the Kaplan-Meier method and curves compared by the log-rank test. Results: median age was 55 years (range, 24 to 77), male sex 92 (51%), Ann Arbor Stage I-II: 32(18%), III-IV: 143 (82%), age > 60 y 70 (39%), Hb < 120 g/L 38 (21%), β2microglobulin > UNV: 45 (25%), LDH > UNV: 34 (19%), bone marrow infiltration 82 (48%), longer diameter of the largest involved node > 6 cm 64 (36%). 47 patients (26%) received rituximab-containing regimens and 124 received conventional chemotherapy regimens (pre-rituximab era). Median follow-up of the series was 66.9 months (range,1.3-221). Using the FLIPI score (n=162) 58 patients (36%) were in the low risk group, 54 (33%) were in the intermediate group and 50 (31%) in the high risk group. Using the FLIPI2 (n=180) 36 patients (20%) were in the low risk group, 103 (57%) in the intermediate group and 41 (23%) in the high risk group. According to FLIPI 5y- PFS rate was 79% for the low risk group, 63% for the intermediate group and 32% for the high risk group, p < 0.001. According to FLIPI2 score, 5y-PFS rate was 82% for the low risk, 54% for the intermediate and 43% for the high risk groups, p=0.017. Concerning OS, applying the FLIPI, 5y-OS rate for the low, intermediate and high risk groups were 94%m 84% and 64%, respectively, p=0.003. Using the FLIPI2, 5y-OS for the low, intermediate and high risk groups were 96%, 80% and 67% respectively, p=0.006. Conclusions: in our experience the FLIPI2 score is a reproducible prognostic index in patients with follicular lymphoma although the FLIPI score seems to discriminate better between groups than the FLIPI2 score. Disclosures: No relevant conflicts of interest to declare.

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Rituximab Maintenance Benefits Less for Follicular Lymphoma Patients with Low Risk of the Follicular Lymphoma International Index

Blood ◽

10.1182/blood-2021-147114 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3544-3544

Author(s):

Tingyu Wang ◽

Ru Li ◽

Rui Lv ◽

Ying Yu ◽

Jiawen Chen ◽

...

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

Progression Free Survival ◽

Risk Groups ◽

Low Risk ◽

Control Group ◽

Intermediate Risk ◽

Free Survival ◽

Rituximab Maintenance ◽

Risk Patients

Abstract Background Follicular lymphoma (FL) is an incurable indolent disease with a heterogeneous course. The Follicular Lymphoma International Prognostic Index (FLIPI) is the most commonly used prognostic system to predict survival. Rituximab-based immunochemotherapy is now the standard choice for the first-line therapy of FL, followed by rituximab maintenance (RM) in patients with response, which prolongs the progression-free survival (PFS). However, the role of RM in different FLIPI risk groups has never been studied as we know. In this study, we aimed to illustrate the effect of RM in FLIPI risk groups. Methods Newly diagnosed FL patients at our center were enrolled in this analysis. All the patients received the rituximab-based chemoimmunotherapy induction regimens. Response assessments were determined according to Lugano's 2014 criteria. Patients who didn't respond to induction were excluded. Categorical variables were compared using Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results From May 2003 to September 2020, 203 newly diagnosed FL were included. 192 patients (95.0%) achieved remission (complete response, CR/partial response, PR) after immunochemotherapy induction, of whom 96 patients continued rituximab maintenance therapies every 3 months for 1-2 years (RM group) (median 7 times，range 4 to 12). 96 patients received no maintenance or fewer than 4 times (control group) (median 0 times, range 0-3). There were no significant differences in baseline characteristics other than the Ann Arbor stage and pathological grade. The RM group patients were more likely to be at low grade (71.8% vs 54.9%, P = 0.042) and advanced stage (90.6% vs 78.7% , P = 0.027) (Table 1). After a median follow-up of 36.4 months (95% confidence interval [CI], 32.2 to 40.6), median OS and PFS were not reached. The 5-year OS rates and PFS rates were 95.1% (95%CI, 90.2%-100%) and 83.0% (95%CI, 75%-91%)(Fig 1). And RM significantly prolonged the PFS, with 5-year PFS rates 92.2% (95%CI, 85.1%-99.3%) and 70.3%(95%CI, 55%-85.6%) (P = 0.0003) (Fig 2). According to FLIPI risk stratification, patients were classified into low-risk, intermediate-risk, and high-risk groups. The 5-year PFS rates were 97.7% (95%CI, 93.2%-100%), 84.7% (95%CI, 70.4%-99%), and 67.8% (95%CI, 49%-86.6%), respectively (Fig 3). For low-risk patients, there was no significant difference in PFS for the RM group vs the control group. However, for both intermediate risk and high-risk patients, PFS was significantly longer in the RM group compared to the control group (P < 0.0001). The PFS rates at 5 years in intermediate-risk patients were 100% and 77.8% (95%CI, 40.8%-92.6%), for the RM group vs control group, high risk 76.4% (95%CI, 54.3%-98.5%), and 54.9% (95%CI, 21.6%-88.2%), respectively (Fig 4). Conclusion Standard rituximab maintenance significantly prolongs progression-free survival in FLIPI intermediate risk and high-risk patients with FL, but not in the FLIPI low risk group. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

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Neither the FLIPI Nor the FLIPI2 Accurately Segregates Low- Risk From Intermediate- Risk Follicular Lymphoma Patients in Terms of Progression-Free Survival

Blood ◽

10.1182/blood.v118.21.2663.2663 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2663-2663

Author(s):

Inas El-Najjar ◽

Janet Matthews ◽

John Gribben ◽

Silvia Montoto

Keyword(s):

Follicular Lymphoma ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Free Survival ◽

Study Population

Abstract Abstract 2663 Background: Follicular Lymphoma International Prognostic Index (FLIPI) is the most frequently used prognostic index for risk stratification in follicular lymphoma (FL) patients. The FLIPI was designed retrospectively in the pre-rituximab era, with overall survival (OS) as the end-point. Follicular Lymphoma International Prognostic Index 2 (FLIPI2) is a more recent index designed prospectively in the rituximab era to overcome these drawbacks. Aim: To compare the efficacy of the FLIPI and FLIPI2 prognostic indexes in discriminating patients with FL with a distinct outcome in terms of OS and progression-free survival (PFS). Patients: From 1985 to 2007, 302 patients were newly diagnosed with grade 1–3a FL in our institution. The FLIPI could be retrospectively assigned in 220 patients and the FLIPI2 in 149 patients. The 122 patients (47 male/75 female; median age: 56 years –range: 25–87) in whom both the FLIPI and FLIPI2 indexes were assessable constitute the study population. Seventy-five patients (61%) received treatment immediately after diagnosis (of which, 25 patients received rituximab containing regimens), whereas the remainder were managed expectantly. Main characteristics at diagnosis are as follows: age>60 years, 41%; stage III-IV, 70%; Hb<12 g/L, 17%; bone marrow involvement, 45%; largest lymph node diameter>6cm, 26%; B2M>ULN, 20% and LDH>ULN, 17%. The median follow-up for alive patients was 86 months (range: 12– 270). Results: Five-year OS and PFS were 74% (95%CI: 69–79) and 38% (95%CI: 32–44), respectively, for the 302 patients. There were no significant differences in the outcome of these patients in comparison with the 122 patients comprising the study population. The distribution of the 122 patients according to the FLIPI and FLIPI2 as well as the 5-year OS and 5-year PFS are shown in the table. The FLIPI and the FLIPI2 indexes predicted OS (p<0.0001 both for the FLIPI and the FLIPI2), but the FLIPI2 did not accurately separate patients with low-risk from those with intermediate risk in terms of OS (p=0.3). The FLIPI score predicted PFS (p=0.001) but was not able to discriminate patients with low-risk from those with intermediate-risk (p=0.6). There was a trend for the FLIPI2 to predict PFS (p=0.06) but it did not segregate the low-risk group from the intermediate-risk group (p=0.3) Conclusions: The FLIPI separates patients into 3 risk groups, well-balanced in terms of the proportion of patients in each group with a distinct OS. In contrast the, majority of the patients fall into the intermediate risk group according to the FLIPI2, and overlaps with the low risk group in terms of OS. With regards to PFS, both indexes are poor at separating low and intermediate risk groups. In summary, both indexes are good at defining a relatively small high-risk population but do not accurately segregate the rest. FLIPI2 does not appear to be superior to FLIPI for risk stratification. This supports that the future lies in uncovering biological factors that might help in the guidance of treatment, in addition to segregating patients more accurately into specific risk groups. Disclosures: Gribben: Roche: Honoraria; Genentech: Honoraria; GSK: Honoraria; Muundipharma: Honoraria. Montoto:Genentech: Research Funding; Roche: Honoraria.

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EUTOS Score Identifies Cases with Poor Outcome in Patients with Early Chronic Phase Chronic Myeloid Leukemia, Though Not Predictive for Optimal Response to Imatinib

Blood ◽

10.1182/blood.v120.21.3778.3778 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3778-3778 ◽

Cited By ~ 3

Author(s):

Mario Tiribelli ◽

Massimiliano Bonifacio ◽

Elisabetta Calistri ◽

Gianni Binotto ◽

Elena Maino ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Progression Free Survival ◽

High Risk Group ◽

Low Risk ◽

Molecular Response ◽

Free Survival ◽

Optimal Response ◽

Risk Patients ◽

Eutos Score

Abstract Abstract 3778 Introduction. The EUTOS score has recently been developed by the European Leukemia-Net (ELN) to predict the achievement of an 18-month complete cytogenetic response (CCyR) and progression-free survival in imatinib-treated early chronic phase (ECP) chronic myeloid leukemia (CML) patients. The score uses the percentage of basophils and spleen size to divide patients in 2 groups of low- and high-risk. Since its publication in 2011, however, there have been conflicting reports about the efficacy of EUTOS score. Moreover, scanty data are available on the power of this scoring system to foresee optimal response to imatinib, as defined by ELN recommendations. Aims and Methods. To test the power of EUTOS score in predicting achievement of optimal response to imatinib, as defined by ELN, time to imatinib failure (TTF) and progression-free survival (PFS), we evaluated 265 ECP CML patients treated with front-line standard dose imatinib (400 mg daily) at 5 major hematology centres in the north-eastern area of Italy. Partial cytogenetic response (PCyR) and CCyR were defined as 1–35% and 0% Ph+ metaphases, respectively; major molecular response (MMR) was defined as BCR-ABL <0.1%IS. TTF was measured from the start of imatinib to the date of any of the following events: progression to accelerated or blastic phase, death for any cause at any time, imatinib dose increase (≥ 600 mg/day) for primary or secondary hematologic or cytogenetic resistance. PFS was measured from the start of imatinib to the date of progression to accelerated or blastic phase or death for any cause at any time. Survival probabilities were estimated by the Kaplan-Meier method and compared by log rank test; differences among variables were evaluated by the Fisher's exact test or by Student's t-distribution. Results. A total of 265 consecutive patients with ECP CML were included in this study. The median age was 55 years (range 19–84), with 149 males and 116 females. The median follow-up was 61 months (range 6–136). The median time from diagnosis to imatinib therapy was 0.7 months (range 0 – 7.6). The distribution according to the EUTOS score was: 248 patients (93.6%) in the low risk group and 17 patients (6.4%) in the high risk group. The “optimal response” endpoints to imatinib (i.e. PCyR at 6th months, CCyR at 12th months and MMR at 18th months) were higher in low-risk patients, but did not achieve statistical significance. Specifically, the values were as following: PCyR 86% vs 67% (p=0.055), CCyR 80% vs 63% (p=0.117) and MMR 61% vs 36% (p=0.126). Cumulative incidence of CCyR was comparable in the two groups (88%% in low-risk and 80% in high risk), but time to CCyR was shorter in low-risk patients (6 months) compared to the one in high-risk patients (9 months) (p=0.048) [figure 1]. More importantly, EUTOS score was able to predict long term response to therapy. Indeed, 59% of patients in the high-risk group experienced imatinib failure, compared to 30% in the low-risk group (p=0.027). Moreover also TTF was significant shorter in the high-risk group [figure 2]. Fifty-three patients in the low-risk group (21%) were switched to 2nd-generation TKIs (29 dasatinib, 22 nilotinib, 1 bosutinib, 1 ponatinib), compared to six (35%) in the high-risk group (4 dasatinib, 2 nilotinib). Also PFS rate was significantly worse in patients with high EUTOS score, with 11/248 events (4%) in the low-risk group and 4/17 (23%) in the high-risk cases (p=0.01) [figure 3]. Conclusions. In our study group, the EUTOS score was predictive for long-term outcome of imatinib therapy, both in terms of treatment failure and of progression-free survival. Taking into consideration the ELN definitions of optimal response, there was a trend toward better cytogenetic and molecular response in low-risk patients; the lack of statistical significance could be due to the relatively small number of high-risk cases. Disclosures: No relevant conflicts of interest to declare.

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The efficacy of EORTC risk tables in Japanese patients with non-muscle invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.331 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 331-331

Author(s):

Satoru Muto ◽

Takeshi Ieda ◽

Syou-ichiro Sugiura ◽

Akiko Nakajima ◽

Akira Horiuchi ◽

...

Keyword(s):

High Risk ◽

Survival Time ◽

Risk Group ◽

Progression Free Survival ◽

High Risk Group ◽

Low Risk ◽

Progression Rate ◽

Intermediate Risk ◽

Free Survival ◽

Muscle Invasive

331 Background: To predict recurrence and progression of non-muscle invasive bladder cancer (NMIBC), EORTC risk tables are widely used worldwide. EORTC risk tables were, however, developed on the basis of individual data from 2,596 NMIBC patients included in seven special European Organization for Research and Treatment of Cancer trials. Therefore, it is not clear the efficacy of these risk tables in clinical practice, especially in Japan. I will report the recurrence and progression rate on the basis of EORTC risk tables in Japanese NMIBC patients. Methods: A retrospective analysis of 619 patients with NMIBC treated between January 1998 and 2012 was performed. Patients were divided into three groups on the basis of EORTC risk tables. We compared recurrence- and progression-free survival rates between groups. Recurrence- and progression-free survival was estimated using the Kaplan-Meier method. Results: We evaluated the clinical outcome of 1,032 TUR-Bt. The recurrence rate is 32.3% in low risk group (n=31), 44.5% in intermediate risk group (n=757), and 49.4% in high risk group (n=85). The median recurrence free survival time is 87 months in low risk group, 35 months in intermediate risk group, and 25 months in high risk group. Although there are significant differences in recurrence free survival time between low risk group and intermediate risk group (p=0.0351), there are no significant differences between intermediate risk group and high risk group (p=0.1871). On the other hand, the progression rate is 1.6% in low risk group (n=128), 5.8% in intermediate risk group (n=451), and 18.0% in high risk group (n=294). The median progression free survival time is 176 months in low risk group, 131 months in intermediate risk group, and 109 months in high risk group. There are significant differences in progression free survival time between low risk group and intermediate risk group (p=0.0138), and between intermediate risk group and high risk group (p=<0.0001). Conclusions: There is an urgent need to establish the standard of recurrence risk classification in Japan.

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Clinical and Biological Prognostic Factors in Follicular Lymphoma Patients During Treatment

10.21203/rs.3.rs-275643/v1 ◽

2021 ◽

Author(s):

Ádám Jóna ◽

Anna Kenyeres ◽

Sándor Barna ◽

Árpád Illés ◽

Zsófia Simon

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Follicular Lymphoma ◽

Risk Group ◽

Standardized Uptake Value ◽

Progression Free Survival ◽

High Risk Group ◽

Pet Ct ◽

Significant Difference ◽

Biological Prognostic Factors

Abstract Introduction: Follicular lymphoma (FL) is an indolent yet heterogeneous B-cell lymphoproliferative disorder. Most people respond to treatment well. However, a particular group of patients has a poor prognosis, and these patients are difficult to define.Patients and methods: We retrospectively analyzed FL patients treated at the University of Debrecen in the past 20 years. We investigated prognostic factors that may influence the survival of FL patients.Results: We found a standardized uptake value (SUV)max cut-off value of 9.85 at the staging PET/CT to significantly separate FL patients’ progression-free survival (PFS) (p=0.0003, HR: 0.2560, 95%CI: 0.1232-0.5318). Lymphocyte/ monocyte (Ly/Mo) ratio of 3.45 drawn at diagnosis also significantly predicted PFS (p=0.0324, HR: 1.806, 95% CI: 1.051-3.104). Combining patients’ with staging SUVmax >9.85 and Ly/Mo < 3.45 a high-risk group of FL patients can be identified (p<0.0001, HR: 0.1033, 95%CI: 0.03719-0.2868). Similarly, a significant difference was shown with a SUVmax cut-off of 3.15 at the interim PET/CT (p<0.0001, HR: 0.1535, 95%CI: 0.06329-0.3720). Combining patients with staging SUVmax >9.85 and interim SUVmax >3.15, a high-risk group of FL patients can be identified (p<0.0001, HR: 0.1037, 95%CI: 0.03811-0.2824). The PFS difference is translated into overall survival advantage (p=0.0506, HR: 0.1187, 95%CI: 0.01401-1.005).Discussion: Biological prognostic factors, such as the Ly/ Mo ratio, may improve the prognostic assessment of staging PET/CT. Nevertheless, PFS difference is translated into OS when using a combination of staging and interim SUVmax. We consider investigating additional biological prognostic factors while currently highlighting PET/CT's role in FL.

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MO048MULTICENTRE PROSPECTIVE VALIDATION OF THE URINARY PEPTIDOME-BASED CLASSIFIER CKD273 AS A PREDICTOR OF RENAL FUNCTION DECLINE IN SUBJECTS WITH TYPE 2 DIABETES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa140.mo048 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Morten Lindhardt ◽

Nete Tofte ◽

Gemma Currie ◽

Marie Frimodt-Moeller ◽

Heiko Von der Leyen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Renal Function ◽

High Risk ◽

Risk Group ◽

Cox Model ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Renal Function Decline

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation. Method The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score > 0.154). Results In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p < 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p < 0.01). A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p < 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p<0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p<0.0001). A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p<0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p<0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p<0.0001). Conclusion In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.

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Immune-Related Four-lncRNA Signature for Patients with Cervical Cancer

BioMed Research International ◽

10.1155/2020/3641231 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Jianfeng Zheng ◽

Benben Cao ◽

Xia Zhang ◽

Zheng Niu ◽

Jinyi Tong

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Immune Cell ◽

Risk Group ◽

Pearson Correlation ◽

Characteristic Curve ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Gynecological Malignancy

Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune-related lncRNAs (IRLs) of CC has never been reported. This study is aimed at establishing an IRL signature for patients with CC. A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson correlation analysis between the immune score and lncRNA expression ( p < 0.01 ). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values ( p < 0.05 ) were identified which demonstrated an ability to stratify patients into the low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group in the training set, valid set, and total set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four-IRL signature in predicting the one-, two-, and three-year survival rates was larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four IRLs in the development of CC were ascertained preliminarily.

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The Glasgow whipple risk score to predict pancreas-specific complications after pancreaticoduodenectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.394 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 394-394

Author(s):

Lavanniya Kumar Palani Velu ◽

Vishnuvardhan Chandrabalan ◽

Ross Carter ◽

Colin McKay ◽

Donald McMillan ◽

...

Keyword(s):

High Risk ◽

Serum Amylase ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Prolonged Stay ◽

Increased Risk ◽

Clinically Significant ◽

Serum Crp

394 Background: Pancreas-specific complications (PSC), comprising postoperative pancreatic fistula, post-pancreatectomy haemorrhage, and intra-abdominal collections, are drivers of morbidity following pancreaticoduodenectomy (PD). Intra-operatively derived pancreatic gland texture is a major determinant of postoperative PSC. We have previously demonstrated that a postoperative day 0 (PoD0) serum amylase ≥ 130 IU/L is an objective surrogate of pancreatic texture, and is associated with PSC. We sought to refine the PSC risk prediction model by including serial measurements of serum C-reactive protein (CRP). Methods: 230 consecutive patients undergoing PD between 2008 and 2014 were included in the study. Routine serum investigations, including amylase and CRP were performed from the pre-operative day. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP associated with clinically significant PSC. Results: 95 (41.3%) patients experienced a clinically significant PSC. ROC analysis identified post-operative day 2 (PoD2) serum CRP of 180 mg/L as the optimal threshold (P=0.005) associated with clinically significant PSC, a prolonged stay in critical care (P =0.032), and a relaparotomy (P = 0.045). Patients with a PoD0 serum amylase ≥ 130 IU/L who then developed a PoD2 serum CRP ≥ 180 mg/L had a higher incidence of postoperative complications. Patients were categorised into high, intermediate and low risk groups based on PoD0 serum amylase and PoD2 serum CRP. Patients in the high risk group (PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l) had significantly higher incidence of PSC, a return to theatre, prolonged lengths stay (all P≤ 0.05) and a four-fold increase in perioperative mortality compared patients in the intermediate and low risk groups (7 deaths in the high risk group versus 2 and nil in the intermediate and low risk groups respectively). Conclusions: A high risk profile, defined as PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l, should raise the clinician’s awareness of the increased risk of clinically significant PSC and a complicated postoperative course following pancreaticoduodenectomy.

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Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score

Blood ◽

10.1182/blood-2010-12-319038 ◽

2011 ◽

Vol 118 (3) ◽

pp. 686-692 ◽

Cited By ~ 257

Author(s):

Joerg Hasford ◽

Michele Baccarani ◽

Verena Hoffmann ◽

Joelle Guilhot ◽

Susanne Saussele ◽

...

Keyword(s):

High Risk ◽

Kinase Inhibitors ◽

Prognostic Score ◽

Progression Free Survival ◽

Risk Groups ◽

High Risk Group ◽

Prognostic Scores ◽

Imatinib Treatment ◽

Free Survival ◽

Eutos Score

AbstractThe outcome of chronic myeloid leukemia (CML) has been profoundly changed by the introduction of tyrosine kinase inhibitors into therapy, but the prognosis of patients with CML is still evaluated using prognostic scores developed in the chemotherapy and interferon era. The present work describes a new prognostic score that is superior to the Sokal and Euro scores both in its prognostic ability and in its simplicity. The predictive power of the score was developed and tested on a group of patients selected from a registry of 2060 patients enrolled in studies of first-line treatment with imatinib-based regimes. The EUTOS score using the percentage of basophils and spleen size best discriminated between high-risk and low-risk groups of patients, with a positive predictive value of not reaching a CCgR of 34%. Five-year progression-free survival was significantly better in the low- than in the high-risk group (90% vs 82%, P = .006). These results were confirmed in the validation sample. The score can be used to identify CML patients with significantly lower probabilities of responding to therapy and survival, thus alerting physicians to those patients who require closer observation and early intervention.

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Validation of Clinical Prognostic Models and Integration of Genetic Biomarkers of Drug Resistance in CLL Patients Treated with Ibrutinib

Blood ◽

10.1182/blood-2018-99-110326 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 186-186 ◽

Cited By ~ 2

Author(s):

Inhye E. Ahn ◽

Xin Tian ◽

Maher Albitar ◽

Sarah E. M. Herman ◽

Erika M. Cook ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Prognostic Models ◽

Discovery Cohort ◽

Treatment Naïve ◽

Equity Ownership

Abstract Introduction: We previously reported a prognostic scoring system in CLL using pre-treatment factors in patients treated with ibrutinib [Ahn et al, 2016 ASH Annual Meeting]. Here we present long-term follow-up results and validation of the prognostic models in a large independent cohort of patients. We also determine the incidence of resistance-conferring mutations in BTK and PLCG2 genes in different clinical risk groups. Methods and Patients: The discovery cohort comprised 84 CLL patients on a phase II study with either TP53 aberration (deletion 17p or TP53 mutation) or age ≥65 years (NCT01500733). The validation cohort comprised 607 patients pooled from four phase II and III studies for ibrutinib in treatment-naïve or relapsed/refractory CLL (NCT01105247; NCT01578707; NCT01722487; NCT01744691). All patients received single-agent ibrutinib 420mg once daily. We used Cox regression models to identify independent predictors of PFS, Kaplan-Meier method to estimate probabilities of PFS, log-rank test to compare PFS, and Cochran-Armitage trend test to compare the incidence of mutation among subgroups. We used R version 3.5.0 or SAS® version 9.3 for statistical analyses. For biomarker correlation, we tested cellular DNA or cell-free DNA collected from patients in the discovery cohort with the targeted sequencing of BTK and PLCG2 genes. Result: At a median follow-up of 5.2 years, 28 (33.3%) of 84 patients in the discovery cohort progressed or died. 52 (61.9%) patients had treatment-naïve CLL. Independent factors of PFS on univariate analysis were; TP53 aberration, prior treatment, and β-2 microglobulin (B2M) >4mg/L (P<0.05 for all tests). Unmutated IGHV and advanced Rai stage (III/IV) showed a trend toward inferior outcome without reaching statistical significance. Because higher levels of B2M were associated with relapsed/refractory CLL, we performed two multivariate Cox regression models to assess B2M and prior treatment status separately. Risk groups were determined by the presence of TP53 aberration, advanced Rai stage, and B2M >4mg/L for Model 1, and TP53 aberration, advanced Rai stage, and relapsed/refractory CLL for Model 2 (Table 1). The high-risk group had all three adverse risk factors; the intermediate-risk group had two risk factors; and the low-risk group, none or one. The median PFS of the high-risk group was 38.9 months for Model 1 and 38.4 months for Model 2, and was significantly shorter than those of intermediate and low-risk groups. In the validation cohort, 254 (41.8%) of 607 patients progressed or died at a median follow-up of 4.2 years. 167 (27.5%) patients had treatment-naïve CLL. Both models showed statistically significant differences in PFS by risk groups (Table 1). For the high-risk group, 4-year PFS was 30.2% in Model 1 and 30.5% in Model 2, which were inferior to those of intermediate (53.4 and 52.4%) and low-risk groups (68.7 and 73.7%). Model 1 classified 20% of patients and Model 2 classified 28% of patients to the high-risk group. BTK and PLCG2 mutations are common genetic drivers of ibrutinib resistance in CLL. To determine whether the incidence of these mutations correlates with prognostic risk groups, we performed targeted sequencing of BTK and PLCG2 of samples collected from patients in the discovery cohort. We used cell-free DNA for patients who received long-term ibrutinib (≥3 years) and had low circulating tumor burden, and cellular DNA, for samples collected within 3 years on ibrutinib or at progression. Of 84 patients, 69 (82.1%) were tested at least once, and 37 (44.0%) were tested at least twice. The frequency of testing was similar across the risk groups by two models (P>0.05). The cumulative incidences of mutations at 5 years in the low-, intermediate-, and high-risk groups were: 21.4%, 44.8% and 50%, respectively, by Model 1 (P=0.02); and 22.6%, 41.4% and 66.7%, respectively, by Model 2 (P=0.01). Conclusion: We developed and validated prognostic models to predict the risk of disease progression or death in CLL patients treated with ibrutinib. Risk groups classified by three commonly available pre-treatment factors showed statistically significant differences in PFS. The clinically-defined high-risk disease was linked to higher propensity to develop clonal evolution with BTK and/or PLCG2 mutations, which heralded ibrutinib resistance. Disclosures Albitar: Neogenomics Laboratories: Employment. Ma:Neogenomics Laboratories: Employment. Ipe:Pharmacyclics, an AbbVie Company: Employment, Other: Travel; AbbVie: Equity Ownership. Tsao:Pharmacyclics LLC, an AbbVie Company: Employment. Cheng:Pharmacyclics LLC, an AbbVie Company: Employment. Dean:CTI BioPharma Corp.: Employment, Equity Ownership; Pharmacyclics LLC, an AbbVie Company: Employment, Equity Ownership. Wiestner:Pharmacyclics LLC, an AbbVie Company: Research Funding.

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