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

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

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A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

10.21203/rs.3.rs-117490/v1 ◽

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.

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

Vojnosanitetski pregled ◽

10.2298/vsp140115014s ◽

2015 ◽

Vol 72 (6) ◽

pp. 483-488

Author(s):

Olivera Simonovic ◽

Lana Macukanovic-Golubovic ◽

Bosko Andjelic ◽

Darko Antic ◽

Biljana Mihaljevic

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Treatment Decision ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Prognostic Groups

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

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Academic Centers Are Associated with Improved Survival Outcomes in High Risk Diffuse Large B-Cell Lymphoma Patients

Blood ◽

10.1182/blood-2018-99-115578 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4747-4747

Author(s):

Daniel A. Ermann ◽

Victoria Vardell Noble ◽

Avyakta Kallam ◽

James O. Armitage

Keyword(s):

Overall Survival ◽

High Risk ◽

Median Survival ◽

Risk Score ◽

B Cell Lymphoma ◽

Risk Groups ◽

Low Risk ◽

Survival Outcomes ◽

Intermediate Risk ◽

Hazard Ratios

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and is characterized as a heterogenous disease associated with varying outcomes. The International Prognostic Index (IPI) has been the standard for baseline prognostic assessment in these patients. In this study we aimed to determine the impact of treatment facility (academic versus non-academic centers) on overall survival outcomes in DLBCL patients stratified by IPI score risk groups, with a focus on high risk disease as this is associated with poorer outcomes. Methods: The 2018 National Cancer Database (NCDB) was utilized for patients diagnosed with DLBCL between 2004-2015. Patients were then stratified based on IPI risk score from low to high risk. Four risk groups were formed: low (0-1), low-intermediate (2), high-intermediate (3), and high (4-5). Overall survival was calculated using Kaplan-Meyer analysis with bivariate cox proportional hazard ratios to compare survival by facility type (academic or community centers) within these risk groups. Results: A total of 160,137 patients were identified. Of these cases 31.8% were classified as low risk, 21.9% were low-intermediate risk, 22.2% were high-intermediate risk, and 24% were high risk. 59.3% of patients were treated at a community center and 40.7% were treated at academic centers. Treatment at academic centers was associated with a significantly improved overall survival (OS) for each risk category. Median survival (in months) for high risk IPI score DLBCL was 47.9 months in community and 61.1 months in academic centers (p<.0001). Median survival for high-intermediate risk score was 48.3 months in community and 87.3 months in academic centers (p<.0001). Median survival for low-intermediate score was 90.3 months in community and 122.8 months in academic centers (p<.0001). Median survival for low risk score was 132 months in community and 148 months in academic centers (p<.0001). Hazard ratios for academic center versus community center for high risk, high-intermediate, low-intermediate and low risk are 0.768, 0.71, 0.848 and 0.818 respectively (p<.0001). Conclusions: Facility type is significantly associated with improved survival outcomes across all IPI based risk groups for DLBCL. This benefit is especially significant in higher risk disease where positive outcomes are less common, suggesting treatment at academic centers may be particularly beneficial in these patients. Some of the possible reasons for this difference may include provider experience, increased access to resources, and opportunity for clinical trials. Further investigations into the factors contributing to such disparities should be done to help standardize care and improve outcomes. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood-2019-126656 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2606-2606

Author(s):

Tze Shin Leong ◽

Sen Mui Tan ◽

Lee Ping Chew ◽

Tee Chuan Ong ◽

Siew Lian Chong ◽

...

Keyword(s):

Overall Survival ◽

Treatment Outcome ◽

High Risk ◽

Relapse Rate ◽

Survival Benefit ◽

Risk Group ◽

Prognostic Index ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk

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

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.8554 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 8554-8554

Author(s):

Fatemeh Ardeshir-Larijani ◽

Gary Wildey ◽

Pingfu Fu ◽

Afshin Dowlati

Keyword(s):

Overall Survival ◽

High Risk ◽

Risk Model ◽

Cox Regression ◽

Cox Model ◽

Prognostic Index ◽

Low Risk ◽

Intermediate Risk ◽

Entire Cohort ◽

Clinical Genomic

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

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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 ◽

10.1182/blood-2020-141699 ◽

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 >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 <120 g/L) in 60% (33/55), thrombocytopenia (platelet counts <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< 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< 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.

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Impact of metastasectomy on progression free and overall survival in metastatic renal cell carcinoma: Analysis of the REMARCC registry.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.753 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 753-753

Author(s):

Margaret Frances Meagher ◽

Ricardo Autorino ◽

Maximilian Kriegmair ◽

Maria Carmen Mir ◽

Jose Rubio ◽

...

Keyword(s):

Risk Factors ◽

Renal Cell Carcinoma ◽

Overall Survival ◽

High Risk ◽

Renal Cell ◽

Risk Groups ◽

Low Risk ◽

Risk Category ◽

Intermediate Risk ◽

Independent Risk Factors

753 Background: The role of metastasectomy has been in flux as treatment paradigms for management of metastatic renal cell carcinoma (mRCC) have shifted. We examined outcomes of surgical metastasectomy stratified in the setting of different mRCC risk groups. Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was subdivided by Motzer RCC criteria (low, intermediate, and high risk), and impact of metastasectomy was analyzed via multivariable analysis (MVA) and Kaplan Meier analyses (KMA). Primary outcome was progression free survival (PFS) and secondary outcome was overall survival (OS). Results: 438 patients (46 low risk, 262 intermediate risk, 140 high risk) with median follow-up 16 months were analyzed. Metastasectomy was performed in 18 (39%), 63 (24%), and 32 (23%) of low, intermediate and high risk groups (p=0.04). Risk groups differed significantly with respect to ECOG performance status (p<0.001), metastases at diagnosis (low 1.72, intermediate 3.49, high 6.45, p<0.001), hemoglobin (p<0.001) and LDH (p<0.001). MVA for PFS revealed age (OR=1.03, p=0.05), BMI (OR=1.05, p=0.01), and higher risk category [vs. low (referent) intermediate OR=7.4, p<0.001, high OR=3.4, p=0.01] to be independent risk factors. MVA for OS revealed age (OR=1.03, p=0.02), BMI (OR=1.06, p=0.01), and higher risk category [low (referent) vs. intermediate OR=2.8, p=0.03, high OR=2.3, p=0.01] to be independent risk factors. KMA for PFS demonstrated that metastasectomy was associated with longer PFS in intermediate (24.0 vs. 6.7 months, p=0.01) but not high risk (4.2 vs. 4.0 months, p=0.58) and low risk (p=0.51) groups. KMA for OS demonstrated that metastasectomy was associated with longer median OS in the intermediate (56.9 vs. 29.3 months, p=0.01) and high risk (18.2 vs. 10.5, p=0.01), but not low risk (p=0.21) groups. Conclusions: Receipt of metastasectomy was associated with improved PFS in intermediate risk and improved OS in intermediate and high risk mRCC patients. These findings challenge prevailing assumptions about utility of metastasectomy. Further investigation is requisite to refine criteria for employment.

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Possibility of a Risk-Adapted Treatment Strategy for Untreated Aggressive Adult T-Cell Leukemia-Lymphoma (ATL) Based on the ATL Prognostic Index: A Supplementary Analysis of the JCOG9801 Study

Blood ◽

10.1182/blood-2018-99-112734 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1645-1645

Author(s):

Kosuke Toyoda ◽

Kunihiro Tsukasaki ◽

Ryunosuke Machida ◽

Tomohiro Kadota ◽

Takuya Fukushima ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Risk Group ◽

Prognostic Index ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Adult T Cell Leukemia ◽

Ann Arbor ◽

Ecog Ps

Abstract Introduction The JCOG9801 study, a randomized phase III trial of the Japan Clinical Oncology Group (JCOG), compared CHOP every two weeks (CHOP-14) with VCAP-AMP-VECP (mLSG15) for patients with untreated aggressive adult T-cell leukemia-lymphoma (ATL) [J Clin Oncol 2007;25:5458-64]. Based on a higher complete response (CR) rate and marginally better overall survival (OS), we concluded that mLSG15 could be a sufficiently effective regimen at the expense of higher toxicity profiles. However, there was an insufficient mLSG15 effect among patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or those aged ≥56 years, suggesting that mLSG15 is not always a definitive treatment for all patients with aggressive ATL. Thus, identifying patients who should receive mLSG15 is essential. We aimed to conduct a supplementary analysis of patients enrolled in the JCOG9801 study using the ATL prognostic index (ATL-PI) that has been recently advocated for acute- and lymphoma-types of ATL [J Clin Oncol 2012;30:1635-40]. Methods We adopted the "age-adjusted" ATL-PI that was established for ATL patients aged ≤70 years as patients aged between 15 and 69 years were eligible in the JCOG9801 study. Having eliminated "age", this index comprised 4 factors, namely Ann Arbor stage (III or IV), ECOG PS (>1), serum albumin (<3.5 g/dL), and soluble interleukin-2 receptor (sIL-2R; >20,000 U/mL). We excluded patients lacking any factors of the age-adjusted ATL-PI and those with unfavorable chronic type based on the age-adjusted ATL-PI model from patients enrolled in JCOG9801. Subsequently, we categorized the remaining patients into three groups, namely low, intermediate, and high risk, and compared mLSG15 and CHOP-14 in terms of OS, treatment CR rate, and toxicity in each risk group. Results Of 118 enrolled JCOG9801 patients, we included 105 patients in this supplementary analysis based on the above criteria, of which 51 and 54 were treated with mLSG15 and CHOP-14, respectively. According to the age-adjusted ATL-PI, these patients were classified as follows: low (n=44, 41.9%), intermediate (n=54, 51.4%), and high (n=7, 6.7%) risks. Regarding patient characteristics, between the two treatment arms, there were no remarkable differences in age, sex, ECOG PS, ATL subtypes, Ann Arbor stage, presence of B symptoms, presence of bulky mass (≥5 cm), and serum albumin, serum calcium, and sIL-2R levels. The mLSG15 arm included 21 (41.2%), 25 (49.0%), and 5 (9.8%) patients in the low-, intermediate-, and high-risk groups, respectively, whereas the CHOP-14 arm included 23 (42.6%), 29 (53.7%), and 2 (3.7%) patients, respectively. We excluded the high-risk group from our analysis due to the small number of patients. mLSG15 did not show any superior trend for OS compared to CHOP-14 in the low-risk group (hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.491-1.868) (Figure A). In contrast, in the intermediate-risk group, better prognosis for OS was observed with mLSG15 (HR: 1.538; 95% CI: 0.841-2.811) than with CHOP-14 (Figure B). Similarly, the CR rate, including the unconfirmed CR rate, did not differ between both arms of the low-risk group (mLSG15 vs. CHOP-14, 47.6% vs. 43.5%), while in the intermediate-risk group, mLSG15 showed a higher CR rate than CHOP-14 (44.0% vs. 13.8%). Regarding toxicity profiles, grade 4 thrombocytopenia was more frequently observed in the mLSG15 arm of both risk groups than in the CHOP-14 arm (66.7% vs. 4.5% in the low-risk group; 68.0% vs. 24.1% in the intermediate-risk group only). There was a higher incidence of grade 4 neutropenia in the mLSG15 arm than in the CHOP-14 arm (100.0% vs. 75.9%) only in the intermediate-risk group. All three treatment-related deaths were documented in the mLSG15 arm of the intermediate-risk group. Conclusions Given the very poor prognosis of ATL, our findings suggest that despite higher toxicities, mLSG15 is more suitable for the intermediate-risk group of age-adjusted ATL-PI, whereas its benefits appear modest in the low-risk group. This supplementary analysis is exploratory; therefore, a further prospective study of aggressive ATL is necessary to confirm these results. Disclosures Tsukasaki: Daiich-Sankyo: Consultancy; Ono Pharma: Consultancy; HUYA: Consultancy, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Research Funding; Celgene: Honoraria; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Fukushima:NEC corporation: Research Funding. Maruyama:Bristol-Myers Squibb: Honoraria; Solasia Pharma: Research Funding; Pfizer: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Novartis: Research Funding; Otsuka: Research Funding; Astellas Pharma: Research Funding; Abbvie: Research Funding; Mundipharma International: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Biomedis International: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Fujifilm: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Dai-ichi-Sankyo: Honoraria; Dai-Nippon-Sumitomo: Honoraria; Asahi Kasei Pharma: Honoraria; AstraZeneca: Research Funding; Amgen Astellas BioPharma: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Nagai:SymBio Pharmaceuticals Limited: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Solasia Pharma K.K.: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer Yakuhin Ltd.: Research Funding; Abbvie G. K.: Research Funding; Celgene Corporation: Honoraria, Research Funding; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; AstraZeneca plc.: Research Funding; Roche Ltd.: Honoraria; Esai Co., Ltd.: Honoraria, Research Funding; HUYA Bioscience International: Research Funding; Ono Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Sanofi K. K.: Honoraria; Zenyaku Kogyo Co., Ltd.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; Gilead Sciences Inc.: Honoraria, Research Funding.

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Identification of Eight Surface Molecules with Survival Predictive Power in B Cell Chronic Lymphocytic Leukemia (B-CLL): A Proposal for a Scoring System.

Blood ◽

10.1182/blood.v104.11.2797.2797 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2797-2797

Author(s):

Valter Gattei ◽

Paolo Sonego ◽

Stefania Russo ◽

Riccardo Bomben ◽

Michele Dal Bo ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Predictive Power ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Z Score ◽

Surface Molecules

Abstract Studies of gene expression profiling of B-CLL cells revealed a phenotype related to experienced B cells, although only a subset of B-CLLs has IgVH mutations. With the aim to identify the immunophenotypic profile associated with a different prognosis, we investigated by flow cytometry the expression of 36 surface molecules (cell-adhesion molecules, integrins, complement activity regulators, myeloid, T and B markers) in 125 B-CLLs, all characterized for IgVH mutations and survival. To recognize the surface molecules with survival predictive power, univariate Cox proportional-hazards analysis was applied to antigen expression values with overall survival as dependent variable. Once identified the antigens whose expression correlated with a z score of ±2.5 (P<0.005) or greater, the maximally selected log-rank statistics were applied to define the optimal cut-off values yielding the best separation of two subgroups with different survival. According to this approach, the following eight antigens were selected (cut-off values in parenthesis): CD55 (30%), CD62L (30%), CD49c (40%), CD11c (20%), CD54 (50%), CD25 (15%), CD79b (65%), CD38 (30%). The first six antigens had negative z score and therefore were identified as favorable prognosticators, while CD79b and CD38 had positive z score, hence were associated with shorter overall survival (negative prognosticators). To build-up a scoring system, we assigned score “1” to each positive prognosticator when its expression was above the designated cut-off (score “0” if below), and score “0” to each negative prognosticator when its expression was above the cut-off (score “1” if below). A total score ranging from 0 to 8 points was therefore obtained in 102/125 cases in which the expression of all the eight markers was available. Three risk groups were identified: i) high-risk (29 cases), score 0–3; ii) intermediate-risk (38 cases), score 4–6; iii) low-risk (35 cases), score 7–8. These three groups differed greatly for survival probabilities (p=5x10–13 by the log-rank test). All patients belonging to the low-risk group were alive throughout the follow-up duration, whereas mean survivals for intermediate- and high-risk groups were 173 months (p=0.032) and 61 months (p=2.0x10–9), respectively. Several relationship between risk groups and other variables was studied: i) patients included in high- and intermediate-risk groups had the same male to female (M:F) ratio (1.4), while the M:F ratio of patients included in low-risk group (group 3) was lower (0.7); ii) Rai’s stage distribution was comparable in the three groups, with the exception of stage “0”, which was significantly less frequent in the high-risk group (p=0.04); iii) if % IgVH mutations (2% cut-off) was checked, mutated to unmutated (M:UM) ratios were 4.8, 2.6 and 0.8 in low-, intermediate- and high-risk groups, respectively (p=0.006); iv) as compared to high-risk group, low- and intermediate-risk groups were characterized by a higher number of B-CLL cases with a IgVH mutational status consistent with antigen-driven selection (20/24 and 17/26 vs. 7/13). In conclusion, the present study introduces a novel predictive tool based on the expression of eight surface molecules, easily investigable, which can stratifies populations of B-CLL patients in three distinct risk categories.

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MDS-Specific Comorbidity Index (MDS-CI) Identifies Overall Survival Differences in Myelodysplastic Syndrome Patients,

Blood ◽

10.1182/blood.v118.21.3793.3793 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3793-3793

Author(s):

Massimo Breccia ◽

Vincenzo Federico ◽

Giuseppina Loglisci ◽

Roberto Latagliata ◽

Michelina Santopietro ◽

...

Keyword(s):

High Risk ◽

Prognostic Index ◽

Organ Damage ◽

Low Risk ◽

Intermediate Risk ◽

High Risk Patients ◽

Significant Difference ◽

Risk Patients ◽

Comorbidity Index ◽

Very High

Abstract Abstract 3793 MDS-specific comorbidity index (MDS-CI) is a score reported by the Pavia group for myelodysplastic syndromes (MDS) patients. This score is a time-dependent index developed for predicting the effect of comorbidities on outcome of these subjects. We applied this score on a total of 450 MDS patients: comorbidities were recorded at the time of diagnosis and considered by medical staff for the analysis. All patients were consecutively diagnosed and followed at our institute in a period between January 1992 and December 2006. Statistical analysis was carried out using SPSS software; survival was defined as time from diagnosis to last contact or death for any cause. Median age of the whole population was 69 years (range 21–88), with a prevalence of male sex (ratio m/f 1.6). Overall, we found the presence of one or more comorbidities in 94% of the examined patients. The most common comorbidities were cardiac disorders observed in 40% of patients, followed by diabetes with organ damage recorded in 22 cases. Application of MDS-CI score identified 300 patients with score 0, 55 patients with score 1, 80 patients with score 2 and 15 patients with score >2. We found significant differences in OS according to MDS-CI stratification: from 38 months for low risk patients (score 0) to 22 months for high-risk patients (score >2, p=0.02). We then evaluated the prognostic effect of MDS-CI on patients stratified according to WPSS prognostic index. WPSS application was possible in 330 of 450 patients who entered the analysis (73%), due to cytogenetic availability of data: we identified 112 patients (34%) with very low/low risk, 137 patients (41.5%) with intermediate risk and 81 patients (24.5%) with high/very high risk. As reported by the Pavia group, we assessed prognostic relevance of comorbidities in very low/low risk WPSS patients, intermediate and high/very high-risk patients. We found in the first category a significant difference in OS stratification: from 48.5 months for patients with score 0 to 20.4 months for patients with score >2 (p=0.002). In WPSS intermediate risk we found similar significant OS difference: from 32.3 months for patients with score 0 to 18.3 months for patients with score 2 (p=0.001). Conversely, we did not find significant differences in WPSS high/very high-risk patients. We also found significant correlations between presence of comorbidities at baseline, as stratified with MDS-CI, and risk of non-leukemic death: from 22% in patients without comorbidities to 75% in patients with score >2 according to MDS-CI (p=0.002). Our analysis showed the efficacy of MDS-CI on a large series of MDS consecutively seen, diagnosed and followed in a single center while strengthening the results reported by the Pavia group: in fact, the value of comorbidities was confirmed in a cohort of patients similar to that observed in the original paper, in terms of median age (69 years in our series vs 66 years in the Pavia series), but with higher percentage of patients with intermediate WPSS risk (41.5% in our series vs 18% in the Pavia population). MDS-CI is a very valid tool capable to differentiate MDS patients with very low/low and intermediate WPSS risk in terms of OS and non-leukemic death risk. Disclosures: Alimena: Novartis: Honoraria; Bristol Myers Squibb: Honoraria.

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