RBC-Transfusion Dependency Improves the Prognostic Value of the Revised-IPSS in MDS Patients: Analysis of South Australian and Dusseldorf MDS Registries

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1998-1998
Author(s):  
Deepak Singhal ◽  
Corinna Strupp ◽  
Rakchha Chhetri ◽  
Monika M Kutyna ◽  
L Amilia Wee ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Validation Cohort ◽  
Prognostic Index ◽  
Scoring Systems ◽  
Risk Groups ◽  
Transfusion Dependency ◽  
Cox Proportional Hazard Regression ◽  
Prognostic Scoring Systems ◽  
Rbc Transfusion

Abstract RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor survival in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International prognostic Scoring System (IPSS-R) includedthree haemoglobincut-offs, which were thought to substitute for RBC-TD. Thus, none of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R, in addition to that offered by haemoglobin levels at diagnosis. South Australian MDS registry (SA-MDS registry) data were used to derive a prognostic index while Dusseldorf registry (Germany) data was used as a validation cohort. Inclusion criteria for this study were: primary MDS not treated with disease-modifying therapy, bone marrow blasts ≤30% and peripheral blasts ≤20%. RBC TD was defined as at least one unit of packed red cells transfused every eight weeks for four months (mos), according to WPSS classification. In this study IPSS-R was calculated at the time of diagnosis and the RBC-TD was continuously reassessed after diagnosis. In South Australian Registry, the prevalence of RBC-TD at diagnosis was 61/295 (20.7%), while the incidence of RBC-TD during follow-up was 64/234 (27.4%; Table I). The poor prognosis associated with RBC-TD was demonstrated in a series of landmark analyses. The median overall survival (OS) of RBC-TD patients was significantly inferior to RBC transfusion independent (RBC-TI) patients at 6mos (18 vs. 64 months; n=255; p < 0.0001), 12mos (24 vs. 71 months; n=231; p < 0.0001) and 24mos (40 vs. 87 months; p < 0.0001; n=173; Fig 1A-C). Subgroup analysis of IPSS-R Low and Intermediate risk groups also showed inferior OS in RBC-TD compared to RBC-TI within each risk category. The adverse prognosis of RBC-TD was substantiated in multivariate analysis using a Cox-proportional regression model. We tested 46 models and in each of the three models with least Akaike Information Criterion (AIC) or minimum AIC difference RBC-TD wasan independent adverse prognostic marker in addition to age, sex, and IPSS-R variables(Wald test; P<0.0001). In the best-fitting model, the IPSS-R variables were used as continuous variables (except IPSS-R cytogenetic risk groups).This Cox-proportional regression model (Table 2) was used to derive a prognostic index using cut-off points determined by Cox's method and was validated in the Dusseldorf cohort. Dusseldorf validation cohort: This cohort consisted of 106 patients (160 start-stop intervals) with a median follow-up of 5.66 years. Cox proportional hazard regression of OS on the prognostic index resulted in a slope coefficient of 0.663 in the validation cohort. This difference in slope could be due to differences between the datasets: e.g. the validation cohort comprised younger patients, more patients with RBC-TD at diagnosis and fewer cases with favourable cytogenetic risk (Table 1). The validation cohort was divided into four prognostic groups using cut-offs determined by Cox's method (derivation dataset). Cox-proportional hazard regression of OS showed significant OS difference between the four prognostic groups (p<0.001) and significantly higher risk of death in groups 3 (p=0.032) and 4 (p=0.007) relative to group 1 (Table 1). Conclusion: Multivariate analysis by Cox proportional hazards regression and serial landmark analysisof dataset clearly demonstrates that development of RBC-TD at any time during the disease course is associated with poor OS, independent of IPSS-R. This was confirmed in the Dusseldorf validation cohort. This is the first report demonstrating that inclusion of RBC-TD can refine the IPSS-R. Furthermore, despite inclusion of three haemoglobin cut-off values in the IPSS-R model, the onset of RBC-TD during follow-up provides additional prognostic value and could be included in future prognostic scoring systems and in treatment decision algorithms for MDS patients. Disclosures Ross: Novartis Pharmaceuticals: Honoraria, Research Funding; BMS: Honoraria.

Validation of the Revised International Prognostic Scoring System in 2582 Patients with Myelodysplastic Syndrome: A Multicenter Study By the Hellenic MDS Study Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2004-2004
Author(s):  
Athanasios Galanopoulos ◽  
Christos K. Kontos ◽  
Nora-Athina Viniou ◽  
Ioannis Kotsianidis ◽  
Vassiliki Pappa ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Performance Status ◽  
Scoring Systems ◽  
Ecog Performance Status ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Transfusion Dependency

Abstract Introduction - Aims: Several prognostic scoring systems have been developed for patients with myelodysplastic syndromes (MDS), including the International Prognostic System (IPSS), the WHO Prognostic Scoring System (WPSS) and the Revised IPSS (IPSS-R). We evaluated the prognostic value of the IPSS-R on an independent group of 2,582 Greek patients with MDS, registered in the Hellenic National MDS Registry. The aim of this multicenter study was to validate the IPSS-R as a predictor for leukemia-free survival (LFS) and overall survival (OS), in newly-diagnosed MDS patients and to compare its prognostic significance with that of IPSS and WPSS. Moreover, to investigate the predictive value of IPSS-R in association with other recognized prognostic variables, such as patient's age, baseline serum lactate dehydrogenase (LDH), and ferritin concentrations, IPSS, WPSS, Eastern Cooperative Oncology Group (ECOG) performance status, transfusion dependency, and response to first-line treatment. Methods: Clinicopathological data from 2,582 MDS patients, diagnosed between 1/2000 - 1/2015 and registered in the Hellenic National MDS Registry were analyzed. Patients with MDS/MPN were excluded. Data included age, gender, date of diagnosis, clinical characteristics, WHO-2008 classification, laboratory parameters, transfusion dependency, bone marrow aspirate and biopsy morphology, cytogenetic findings, and type of treatment. LFS was calculated from the date of initial diagnosis of MDS until bone marrow blast increased to ≥20% [transformation to acute myeloid leukemia (AML), according to the WHO classification], or last contact. OS was defined as the time from MDS diagnosis to death, or last contact. Patients alive and not having developed AML until last follow-up were censored for OS and LFS, respectively. Kaplan-Meier survival analysis and Cox regression analysis were performed with regard to LFS and OS. Differences between Kaplan-Meier curves were evaluated using the Mantel-Cox (log-rank) test. All significant variables identified by univariate Cox regression analysis and clinical factors important for MDS were used to build the multivariate Cox regression models. Multivariate Cox regression analysis included only those patients for whom the status of all variables was known, and comprised age, serum LDH, and ferritin levels, transfusion dependency, response to first-line treatment, IPSS, WPSS, and IPSS-R. Confidence intervals (CI) were estimated at the 95% level; all tests were two-sided, accepting p<0.05 as indicative of a statistically significant difference. All statistical analyses were performed with the statistical software SPSS (version 21). Results: 1,623 male (62.9%) and 959 female MDS patients with a median age of 74 years at diagnosis were included in the current study. Complete follow-up information was available for 2,376 patients. The estimated median OS was 58 months (95% CI = 52.9 - 63.1 months). For 1,974 patients, data used in the calculation of all three scoring systems were complete, thus allowing risk score calculation and comparison of the three risk assessment systems. Median OS was significantly different in patient subgroups classified according to IPSS, WPSS, and IPSS-R, as shown by the Kaplan-Meier survival analysis (p<0.001). Fig. 1 shows Kaplan-Meier OS curves of MDS patients stratified according to IPSS-R (p<0.001). Moreover, the comparison of the prognostic value of the IPSS, WPSS, and IPSS-R revealed that the IPSS-R was significantly superior to both, WPSS and IPSS (p<0.001 in all cases). Multivariate Cox regression analysis demonstrated that the high prognostic value of IPSS-R, in terms of LFS and OS, was independent of patient's age, serum LDH, and ferritin concentration, ECOG performance status, and transfusion dependency (p<0.001). Interestingly, besides IPSS-R, patient age and transfusion dependency retain their small - yet significant - prognostic impact in the multiparametric models, thus implying that these two parameters could add prognostic value to the IPSS-R. Conclusions: Our data support the notion that all three prognostic scores are very useful predictors for both, LFS and OS in MDS, yet IPSS-R is superior to IPSS and WPSS as a prognostic tool, with regard to OS. Disclosures No relevant conflicts of interest to declare.

Myelodysplastic Syndrome (MDS)-Specific Comorbidity Index for Predicting the Impact of Extra-Hematological Comorbidities on Survival of Patients with MDS

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2677-2677 ◽  
Author(s):  
Matteo G Della Porta ◽  
Andrea Kuendgen ◽  
Luca Malcovati ◽  
Esther Zipperer ◽  
Cristiana Pascutto ◽  
...  
Keyword(s):  
Cardiac Disease ◽  
Prognostic Value ◽  
Prognostic Model ◽  
Validation Cohort ◽  
Risk Groups ◽  
Allogeneic Transplantation ◽  
History Of ◽  
Transfusion Dependency ◽  
Comorbidity Index ◽  
The Impact

Abstract Myelodysplastic syndromes (MDS) occur mainly in older persons, who are likely to be affected with extra-hematological comorbidities. Recent findings suggest that proper assessment of comorbidities is useful to predict the outcome of MDS patients receiving allogeneic transplantation. However, the results obtained in this highly selected subset of patients cannot be applied to the whole MDS population. In this study, we evaluated the impact of extra-hematological comorbidities on the natural history of MDS with the aim of developing a specific prognostic index. The patients comprised a “learning cohort”, in which we defined the set of variables to be included in the prognostic model and their weighted scores, and a “validation cohort”, in which we confirmed the prognostic value of the scoring system. The learning cohort included 840 MDS patients diagnosed at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, between 1992 and 2006, while the validation cohort consisted of 504 patients seen at the Heinrich-Heine-University Hospital, Duesseldorf, Germany, between 1982 and 2006. All cases were classified according to the WHO criteria. Patients who underwent allogeneic transplantation or intensive chemotherapy were censored at the time of the procedure. One or more comorbidities were present in 455 (54%) patients in the learning cohort at the time of diagnosis: the older the age, the higher the prevalence. Cardiac disease was the most frequent extra-hematological morbidity (25% of patients) and the main cause (63%) of non-leukemic death (NLD). In a Cox multivariable analysis with time-dependent covariates, the onset of a comorbidity significantly affected the risk of NLD (HR=2.29, P&lt;.001) and worsened overall survival (OS, HR=1.51, P=.01). Patients who developed RBC transfusion-dependency had a significantly higher risk of NLD (HR=4.31 P=&lt;.001), cardiac disease and death (HR 4.16 and HR 4.88, respectively; P=&lt;.001). In this group, serum ferritin levels were significantly associated with the risk of cardiac disease and death (P=.001). The onset of cardiac, liver, renal, pulmonary disease and solid tumor were found to independently affect the risk of NLD in a multivariable Cox regression (HR from 3.57 to 1.97; P values from &lt;0.001 to 0.04). Based on these results, we developed a dynamic prognostic model (MDS-specific comorbidity index, MDS-CI) for predicting the effect on NLD and OS of comorbidities either present at the time of diagnosis or occurring during the follow-up. Risk scores for each comorbidity were estimated from the regression coefficients (Table 1). Table 1. MDS-specific comorbidity index (MDS-CI) Comorbidity Score Cardiac disease 2 Moderate-to-severe hepatic disease 1 Severe pulmonary disease 1 Renal disease 1 Solid tumor 1 Risk groups: Low (score 0), Intermediate (score 1–2), High (score &gt;2). MDS-CI allowed us to identify 3 groups of patients with different probability of NLD and OS (P&lt;.001). The prognostic value of the MDS-CI was then evaluated in the validation cohort of patients, where the 3 MDS-CI risk groups showed significantly different probabilities of NLD (P&lt;.001) and OS (P=.005), with a 2-year risk of NLD since diagnosis of 24%, 42% and 61% in the low, intermediate and high risk group, respectively. In summary, extra-hematological comorbidities significantly worsen the natural history of MDS patients, specifically increasing the risk of NLD. In particular, transfusion-dependency and secondary iron overload are associated with a higher risk of cardiac complications. The MDS-CI improves our ability to stratify the outcome of MDS patients and may be a useful tool for clinical decision-making. An accurate evaluation of extra-hematological comorbidity should be part of the prognostic assessment of patients with MDS.

scholarly journals Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3776
Author(s):  
Edouard Auclin ◽  
Perrine Vuagnat ◽  
Cristina Smolenschi ◽  
Julien Taieb ◽  
Jorge Adeva ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Prognostic Index ◽  
Predictive Marker ◽  
Risk Groups ◽  
Two Factors ◽  
One Year ◽  
Metastatic Sites ◽  
Tumor Types

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p <0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

Inclusion of RBC-Transfusion Dependency Improves the Prognostic Value of Revised-IPSS (R-IPSS) in MDS Patients

2015 ◽  
Vol 15 ◽  
pp. S44
Author(s):  
Devendra K. Hiwase ◽  
Deepak Singhal ◽  
Rakchha Chhetri ◽  
Monika Kutyna ◽  
Peter B. Harrison ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Transfusion Dependency ◽  
Rbc Transfusion

Time Changes In Predictive Power Of MDS Prognostic Scores – Effects On Revised Scores Such As The IPSS-R, Impact Of Age

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1544-1544 ◽  
Author(s):  
Michael Pfeilstöcker ◽  
Heinz Tüchler ◽  
Julie Schanz ◽  
Guillermo Sanz ◽  
Guillermo Garcia Manero ◽  
...  
Keyword(s):  
Lower Risk ◽  
Prognostic Value ◽  
Conflicts Of Interest ◽  
Scoring Systems ◽  
Prognostic Scores ◽  
Risk Category ◽  
Prognostic Scoring Systems ◽  
Prognostic Power ◽  
Risk Categories ◽  
Over Time

Abstract Introduction New, refined prognostic scoring systems have been established for MDS. Most scores assess prognosis at time of diagnosis assuming stable prediction over time. Earlier studies have shown moderate loss of prognostic power over time in scores using clinical parameters whereas cytogenetic scores maintained prognostic power, scores including comorbidity had shown gain of prognostic power (Pfeilstöcker et al, 2012). The aim of this multicenter retrospective study was to assess the relative stability of the newly developed scoring systems over time, to compare and explain observed time-related losses of prognostic power, and to discuss their clinical implications. Methods This study is based on 7212 untreated (no disease modifying treatment) MDS patients from multiple institutional databases of the IWG-PM, which generated the IPSS-R (Greenberg et al, 2012). Patient characteristics were well comparable with other populations: median age 71 years, male gender 60 %, median overall survival 3.8 years (range 3.7-4.0), median time to AML transformation not reached with 25% of patients transforming to AML after 6.8 years. Patients were diagnosed and classified by FAB and WHO; cytogenetics were classified by original IPSS subtypes and by the recently refined proposal integrated into the IPSS-R (Schanz et al, 2012). The following scores were analysed for their stability over time: IPSS, IPSS-R, WPSS variants, cytogenetic scores, age, performance status and other differentiating features of the IPSS-R. Time variations were described by the Cox-zph-test, and by applying Dxy, a measure of concordance, for censored data at separate observation periods. Results In line with previous observations, loss of prognostic power occurred over time after diagnosis in all scoring systems. While for the entire population the risk between adjacent IPSS-R risk categories differs by ∼80%, for patients observed at least 1 year the increase is ∼66%, and for those observed 4 years it is only ∼25%. The IPSS-R and particularly its age-including version (the IPSS-RA) retained the highest prognostic values compared to all other scoring systems at all time points. Dxy for IPSS-R: at diagnosis 0.43, 1 year 0.35, 2 years 0.27, 4 years 0.14. Including age, as in the IPSS-RA, was associated with less loss of prognostic power over time: Dxy at diagnosis 0.46, 1 year 0.38, 2 years 0.31, 4 years 0.22. For the IPSS and WPSS (available for the latter in only 33% cases), these values were: 0.37, 0.30, 0.22, 0.11 and 0.44, 0.36, 0.29, 0.18 respectively. Considering risk categories, the risk remained fairly constant over time for the lower risk categories in every analyzed scoring system, while the risks in the higher risk categories were especially high in the second half of the first year after diagnosis, diminishing thereafter, thus reducing the prognostic value of these categories over time. To determine whether statistical weights optimized for each time period would alter these results, time-specific weights were applied, which did not demonstrate substantially different prognostic values from the basic model analysis. Particularly good retention of prognostic power was found in the lower risk categories over time. The lesser retention of prognostic power in the higher risk categories appeared related to loss of a larger portion of these patients over time due to their deaths or being censored by their beginning treatment. For the IPSS-R intermediate risk category patients, the prognosis for survival approached the “high” category ∼3 years after diagnosis, while it remained intermediate regarding their risk of AML transformation. Conclusions These data demonstrate that a degree of attrition of prognostic value occurred over time from diagnosis for all of the assessed MDS prognostic scoring systems. The IPSS-R, particularly the age-inclusive IPSS-RA, best retained such prognostic capability over time for the untreated patients analyzed. Disclosures: No relevant conflicts of interest to declare.

Treatment Outcome and Prognostic Model for Stage IE/IIE Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Retrospective Study in a Cohort of 305 Patients with Long Term Follow-up

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2718-2718
Author(s):  
Yuankai Shi ◽  
Bo Jia ◽  
Xiaohui He ◽  
Youwu Shi ◽  
Mei Dong ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
T Cell ◽  
Prognostic Model ◽  
Prognostic Index ◽  
Risk Groups ◽  
Natural Killer T Cell ◽  
Combined Chemoradiotherapy ◽  
Radiotherapy Alone ◽  
Killer T Cell

Abstract Background Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare and distinct subtype of non-hodgkin lymphoma (NHL). The frequency was higher in Asia than in western countries and it has become the most common subtype of peripheral T-cell lymphomas in China. The majority of ENKL patients present with early stage. Optimal treatment modalities and prognostic factors for localized ENKL have not been fully defined. This study aimed to evaluate the optimal treatment strategy and prognostic factors for localized ENKL patients. Methods Between 2003 and 2013, three hundred and five patients with stage IE/IIE ENKL were comprehensively analyzed in this study. A total of 180 patients received combined chemoradiotherapy, with 111 patients received radiotherapy alone and 14 patients recieved chemotherapy alone. Chemotherapy regimens include GDP (gemcitabine, cisplatin, and dexamethasone), CHOP (epirubicin, cyclophosphamide, vincristine, and prednisolone) and other regimens. A total dose of 50 Gy to the primary tumor was considered as radical dose for ENKL, and additional 5 to 10 Gy was administered as a boost to the residual disease. Results The complete response (CR) rate for patients received chemoradiotherapy (n=175) was significantly higher than that for patients received radiotherapy alone (n=102) (89.1 % vs.77.5 %, P = 0.009) or chemotherapy alone (n=14) (89.1 % vs.21.4 %, P< 0.001). The median follow up time for all 305 patients was 38.7 (1.1 to 393) months. For 228 stage IE paranasal extension or IIE patients, 3-year overall survival (OS) in combined chemoradiotherapy (n=154), radiotherapy alone (n=60) and chemotherapy alone (n=14) groups were 85.7%, 73.3% and 57.1% respectively (chemoradiotherapy vs. radiotherapy, P=0.003; chemoradiotherapy vs. chemotherapy, P<0.001). For patients received combined chemoradiotherapy, GDP regimen (n=54) (included 10 patients with pegaspargase) could significantly improve 3-year progression-free survival (PFS) compared with CHOP-like (n=110) (included 10 patients with asparaginase) (88.9% vs. 70.9%, P =0.015).Patients received radiotherapy first followed by chemotherapy (n=84) was associated with superior 3-year PFS compared with patients initially received chemotherapy (n=96) (81.0% vs. 69.8%, P=0.034). But for 54 patients received GDP regimen, induction chemotherapy (n=17) could increase 3-year PFS (100.0% vs. 83.8%, P=0.112) and OS (100.0% vs. 86.5%, P=0.180). We identified 3 risk groups based on 3 prognostic factors (stage II, LDH elevated and paranasal extension) with different survival outcomes. The 3-year OS rates were 93.5%, 85.0% and 62.2% respectively for patients with no risk factors, 1 or 2 factors and 3 factors (P<0.001). Conclusions Combined chemoradiotherapy is the most optimal therapy strategy for stage IE paranasal extension or IIE ENKL patients. GDP or combined with pegaspargase regimen shows promising efficacy, significant superior to the traditional CHOP regimen. The sequence of chemotherapy and radiotherapy for patients received novel chemotherapy regimens still needs further assessment in phase 3 clinical trials. We identified 3 risk groups based on 3 prognostic factors (stage II, LDH elevated and paranasal extension) with different survival outcomes and this novel prognostic model may better predict prognosis than previous International Prognostic Index (IPI) and Korean Prognostic Index (KPI) score for ENKL patients with limited stage. Disclosures No relevant conflicts of interest to declare.

Systemic inflammatory response in predicting survival in patients with operable colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 456-456 ◽  
Author(s):  
K. A. Kwon ◽  
S. Oh ◽  
S. Kim ◽  
S. Lee ◽  
J. Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Response ◽  
Survival Data ◽  
Prognostic Score ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Scoring Systems ◽  
Systemic Inflammatory Response ◽  
Lymphocyte Ratio

456 Background: Several inflammatory response materials could be biomarkers for prediction of prognosis of cancer patients; elevated C-reactive protein (CRP), increased white cell, neutrophil, platelet, and decreased albumin. The Glasgow Prognostic Score (GPS) combines circulating CRP and albumin level, the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) has been introduced for prognostic scoring system in colorectal cancer (CRC). Thus, in this study, we attempted to identify an more adequate prognostic model related with systemic inflammatory response for CRC. Methods: Between Mar 2005 and Dec 2008, 200 patients who underwent curative resection for colorectal cancer were enrolled in this study. Systemic inflammatory parameters (CRP, albumin, neutrophil, lymphocyte, and platelet count) were checked for making 3 scoring systems. Based on clinical survival data, we then compared PFS and OS with GPS, NLR, and PLR. Results: Male to female were 123:77. Median age of the patients was 64 years (range, 26-83 years). Median follow-up duration was 27.2 months (range 7.8-52.7 months). 36 patients were observed disease progression or death. 19 patients were passed away during follow-up duration. 3 year PFS and OS were 72% and 86%, respectively. Numbers of GPS 0,1, and 2 patients were 154 (77%), 44 (22%), and 2 (1%), respectively. Survival analysis according to GPS, PFS and OS could not be able to show the prognostic significance (P=0.313 and P=263). Cut-off value of NLR and PLR were determined 3 and 180 by ROC curve. Both of NLR and PLR were observed as a good prognostic biomarker of PFS and OS (P=0.009 and P<0.001 in PFS, P=0.006 and P=0.001 in OS). Conclusions: Although GPS, NLR, and PLR were introduced as prognostic scoring systems for operable CRC, PLR which is constructed of platelet/lymphocyte count may represent a useful prognostic index for the prediction of PFS and OS in operable CRC. No significant financial relationships to disclose.

Prognostic value of post-induction PET/CT in untreated multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21006-e21006
Author(s):  
Lale Kostakoglu ◽  
David Dingli ◽  
Meral Beksac ◽  
Elena Zamagni ◽  
Tomer Martin Mark ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Progression Free Survival ◽  
Scoring Systems ◽  
Prognostic Indicators ◽  
Cell Transplant ◽  
Liver Uptake ◽  
Durable Response ◽  
Pet Ct ◽  
Inadequate Sample Size

e21006 Background: Induction with novel biological agents has significantly improved progression free survival (PFS) of MM pts. However, role and timing of ASCT is unclear and there remains a need for a practical means to predict post-ASCT outcome. Our goal was to determine the prognostic value of FDG PET/CT (PET) after induction therapy (IT) in comparison with other prognostic factors and International Myeloma Working Group (IMWG) response criteria. Methods: Prospective, multicenter study of 113 newly diagnosed MM pts undergoing IT+ASCT. IT was not controlled and consisted of 2 or 3 novel agent combinations. The tested variables to predict PFS are shown in table. Two PET scoring systems were used: Score1, positive>marrow uptake; Score2, positive>liver uptake. ROC analysis determined the SUV cut-off. Results: With a median follow-up of 29.5 mo 56 (49.6%) pts relapsed (median PFS: 24.3 mo). Results are displayed in table. Post-IT, when a "+" PET (Score2) was associated with less than a VGPR response, relapses occurred in 83% of pts vs. in only 30% when PET was "-" and pts were in CR or VGPR. Multivariate analysis revealed only ISS to be an independent predictor of PFS (p=0.014). Conclusions: Post-IT a "-" PET associated with CR+VGPR suggests a durable response. Qualitative PET evaluation using a more liberal threshold (liver) to define positivity can be used to accurately assess response in MM. These data failed to prove the post-IT IMWG and PET response to be independent prognosticators while ISS was a superior predictor. This may be attributed to inadequate sample size, nonuniform pre- and post-ASCT treatments, varying follow-up times. Further analyses with stratifying various prognostic indicators and therapy schemes in a larger population are underway to determine a definitive role for PET as a predictor of post-ASCT outcome. [Table: see text]

Blood mRNA signature to predict survival in patients with metastatic melanoma treated with tremelimumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9080-9080 ◽  
Author(s):  
Yvonne M. Saenger ◽  
Jay Magidson ◽  
Bobby Chi-Hung Liaw ◽  
Karl Wassmann ◽  
William Barker ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Risk Score ◽  
Peripheral Blood ◽  
Validation Cohort ◽  
Risk Groups ◽  
Phase Iii ◽  
Gene Model ◽  
Training Cohort ◽  
Melanoma Patients

9080 Background: Tremelimumab (Ticilimumumab, Pfizer), a monoclonal antibody targeting CTLA-4, a T cell inhibitory molecule, has shown activity in metastatic melanoma. Ipilimumab (Yervoy, BMS), another antibody targettingCTLA-4, improves survival relative to a peptide vaccine and is now FDA approved. A minority of patients will achieve durable tumor control with CTLA-4 blockade and biomarkers are urgently needed to identify those patients. Methods: 170 inflammatory, melanoma-specific and CTLA4-pathway related mRNA transcripts were measured using RT-PCR in pre-treatment peripheral blood samples from 218 patients with refractory melanoma receiving tremelimumab in a multi-center phase II study. A 2-class latent model yielded a risk score based on 4-genes that was highly predictive of survival (p<0.001), and was used to categorize patients into low, medium and high-risk groups. An independent cohort of 260 treatment naïve melanoma patients receiving tremelimumab as part of a multi-center phase III study was then used to validate the risk score as well as the 3 risk groups defined using the pre-specified cut-points. Results: There was no significant difference between the two cohorts in terms of age, gender, stage of disease or ECOG status. Median time of follow up was 297 days for the training cohort and 386 days for the validation cohort. 67% of patients in the training cohort and 70% of patients in the validation died during time of follow-up. Collectively, the ability of the 170 genes to predict survival exhibited a high degree of consistency across the cohorts (p < 0.001). A 4-gene model including cathepsin D (CTSD), Phopholipase A2 group VII (PLA2G7), Thioredoxin reductase 1 (TXNRD-1) and Interleukin 1 receptor associated kinase 3 (IRAK3) predicted survival in the validation cohort (p=0.001 by log rank test). Multivariable cox analysis showed that the 4-gene model added to the predictive value of clinical predictors (p<0.0001). Conclusions: Expression levels of CTSD, PLA2G7, TXNRD1, and IRAK3 in peripheral blood are predictive of survival in melanoma patients treated with ticilimumab (αCTLA-4). Blood mRNA signatures should be further explored to define patient subsets likely to benefit from immunotherapy.

Use of single polymorphism arrays (SNP-A) to modify prognostic scoring systems for myelodysplastic syndromes.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6521-6521
Author(s):  
Manojkumar Bupathi ◽  
Paul Elson ◽  
Visconte Valeria ◽  
Fabiola Traina ◽  
Christine O' Keefe ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Proportional Hazards ◽  
Uniparental Disomy ◽  
Scoring Systems ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Clinical Factors ◽  
Cox Proportional Hazards Models ◽  
Revised Definitions ◽  
Endpoint Data

6521 Background: MDS are hematologic neoplasms characterized by dysplasia and cytopenias. Two commonly used risk stratifications, IPSS (Greenberg et al Blood 1997) and IPSS-R are based on clinical factors (marrow blasts, number of cytopenias and genetic abnormalities determined by conventional karyotyping), with the IPSS based on 4 cytogenetic risk groups and the IPSS-R based on 5 cytogenetic risk groups defined by Schanz et al JCO 2012. A drawback to metaphase cytogenetics (MC) is its inability to detect small cryptic chromosomal defects and uniparental disomy (UPD). SNP-A can identify these small cytogenetic lesions/UPD and has been shown to be of prognostic value in MDS. The goal of this investigation was to determine if SNP-A detected defects could be used to refine the IPSS and IPSS-R. Methods: SNP-A karyotyping was performed as previously described (Tiu et al, Blood, 2011). We reviewed data from 327 patients idenfitying SNP-A results, MC, and the IPSS/IPSS-R-related clinical factors were identified. Overall survival (OS) measured from the date of sampling for SNP-A karyotyping was the primary endpoint. Data were analyzed using Cox proportional hazards models. Results: SNP-A lesions not detected by MC were grouped as 1) none or only gains/losses; 2) UPD only or gains+losses but no UPD; and 3) UPD+other defects. The frequencies/median os in months (mo) of the groups were: 66%/20.0, 23%/12.7 and 11%/5.8, respectively, p<.0001 for OS. Combining the SNP-A groups with MC resulted in revised definitions of cytogenetic risk that had better discrimination than the underlying models; and when combined with the relevant clinical factors resulted in refined IPSS (IPSSSNP-A) and IPSS-R (IPSS-RSNP-A) risk stratifications (Table). Conclusions: Detection of chromosomal gains, losses, and UPD by SNP-A has prognostic value in MDS and can be used to refine current risk stratifications. [Table: see text]

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