Prognostic Assessment of the PET-CT Role in Primary Patients with Hodgkin Lymphoma: Do We Still Need More Data?

Abstract Introduction.PET-CT is the new imaging modality for staging of patients with Hodgkin Lymphoma (HL) with its excellent results in prognostic role for survival rate. Despite this fact, there are still patients in different risk groups who need intensification in treatment or dose de-escalation. In recent years several studies have been activated and published data about baseline, interim (iPET) and end-of-treatment (PET3) PET-CT prognostic role. But somewhere, there are still a lot of controversies. Here we report the results of a multicenter prospective study of iPET and PET3 in HL. Methods .113 patients with the primary HL were evaluated in the study. Between 113 patients 67.2% (76) were females and 32.8% (37) - males, with median age 42.5 years (range - 18 to 67years ). Patients received standart chemotherapy protocols based on risk group - ABVD or BEACOPP-14/esc. Metabolic PET-CT imaging was performed at participating PET centers according to routine protocols. iPET and PET3 with 1-3 and 4-5 scores by Deauville were considered as astatus-negative and status-positive result, respectively.The primary endpoints of the study were evaluated predicting treatment outcome and event free survival (EFS). Results.40.7% (46/113) with early stages were treated by ABVD and 59.3% (67/113) patients with advance stages received BEACOPP-esc/14 and ABVD, respectively (p<0.05). The ORR of 96 patients (CR, PR) was 92%. The maximum follow-up period in this group of patients was 62 months (median 17 months). 98% (111/113) patientsare still followed up. 89% (89/100) and 11% (11/100) of patients had 1-3 and 4-5 scores of iPET by Deauville 5-PS scale, respectively (p < 0.05). In total, disease progression was documented in 27.2% (3/11) of iPET-positive patients and 12.3% (11/89) of iPET-negative patients (p<0.05). There was one death from refractory disease. We did not find anysignificantprognostic roleof iPETanddepends on type of regimen in patients from that group to predict the EFS. Thus, 3-year EFS of patients with iPET-positive versus iPET-negative was 57% and 85%, respectively (Log-rank test, p=0.3). 95.5% (108/113) and 4.5% (5/113) patients in our cohort had PET3- negative (PET3-) and positive (PET3+) status, respectively (p<0.05). The 2-year EFS rates were 90% and 15% for patients whose PET3 was negative and positive, respectively (Log-rank test, p<0.0001). 2-year EFS for pts PET3+ with I-IIA was higher compared in cases with IIB-IVB stages (50% vs 15%,respectively; Log-rank test, p<0.0001). But EFS ratein patients with PET3- depends on stage of disease was similar: 95 % vs 90% in patients with I-IIA vs IIB-IVB, respectively. Conclusion. While performed iPET provides valuable information about the quality of the treatment response, there is still a need for its prospective confirmation as a prognostic factor. Clinical trials are designed to improve upon the current 1st-line therapy, may be more informative, if focused on PET-positive patients after treatment. Disclosures No relevant conflicts of interest to declare.

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Comorbidity Is An Independent Prognostic Factor in AML: Comparison of Two Comorbidity Scores.

Blood ◽

10.1182/blood.v114.22.3106.3106 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3106-3106

Author(s):

Juergen Novotny ◽

Achim Aisenbrey ◽

Holger Nückel ◽

Ulrich Dührsen

Keyword(s):

Prognostic Factor ◽

Median Survival ◽

Hematopoietic Cell Transplantation ◽

Conflicts Of Interest ◽

Risk Groups ◽

Independent Prognostic Factor ◽

Rank Test ◽

Log Rank Test ◽

Comorbidity Scores ◽

Comorbidity Index

Abstract Abstract 3106 Poster Board III-43 Objective Many factors have been studied to predict outcome and allocate treatment in AML. The best established prognostic factors are karyotype and age. However, comorbidity may play an important role in the outcome of AML. We applied two comorbidity scores at the time of first admission in order to test this hypothesis. Methods We retrospectively analysed 198 consecutive patients with AML. All patients were included irrespective of the applied therapy. Karyotype risk group was 11.6 % good, 68.0 intermediate and 20.4 % poor risk, respectively. The median survival was 382 days. The median age was 62 years (range 20 – 81), 95 were male, 103 were female. The criteria of the Charlson Comorbidity Index (CCI) and the recently developed Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) were applied. However, the cut-offs were set lower than in the original publication in order to detect the possible impact of minor comorbidity. Results In our study, the HCT-CI (left figure) separated clearly between patients with a score of more than one (dotted line), one (dashed line) and zero (continous line) (median survival: 100 vs 328 vs 718 days; log rank test p<0.0001). Similarly, the CCI separated the patients with more than one (dotted line), one (dashed line) and none (continous line) (median survival: 94 vs 293 vs 515 days; log rank test p<0.0001). Karyotype (p < 0.001), HCT-CI (p = 0.003) and age (cut-off 60 years; p = 0.006) we shown as independent risk factors by multivariate analysis. The CCI (right figure) separated only between patients with a score of zero (continous line) and those with at least one score point. Patients with one (dashed line) and patients more than one (dotted line) were not separated. Conclusions Our findings show that HCT-CI is an additional prognostic factor in AML, at least in our cohort. We extend previous findings severalfold. Firstly, our analysis includes 90 patients younger than 60 years and was not restricted to patients older than 60 years. Secondly, we directly compared two comorbidity indices, showing that the HCT-CI discriminaates between three risk groups. Thirdly, we showed that comorbidity is an independent predictor for survival. In conclusion comorbidity seems to be an independent prognostic factor and should be studied prospectively to clarify its use for stratification in therapeutic studies. Disclosures No relevant conflicts of interest to declare.

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A Score for Predicting Freedom from Progression of Children and Adolescents with Hodgkin Lymphoma

Hemato ◽

10.3390/hemato2020016 ◽

2021 ◽

Vol 2 (2) ◽

pp. 264-280

Author(s):

Valli De Re ◽

Laura Caggiari ◽

Maurizio Mascarin ◽

Mariangela De Zorzi ◽

Caterina Elia ◽

...

Keyword(s):

Children And Adolescents ◽

Hodgkin Lymphoma ◽

Rank Test ◽

Log Rank Test ◽

Kaplan Meier ◽

Positron Emission ◽

Pet Ct ◽

Risk Patients ◽

Better Than

Several studies have examined the prognostic performance of therapeutic groups (TG) and early responses to therapy on positron emission tomography/computed tomography (PET/CT) in children and adolescents with classical Hodgkin lymphoma (cHL); less research has been performed on molecular parameters at diagnosis. The aim of the present study was to devise a scoring system based on the TG criteria for predicting freedom from progression (FFP) in 133 patients: 63.2% males; 14 years median age (interquartile range (IQR) 11.9–15.1); with cHL (108 nodular sclerosis (NS) subtype) treated according to the AIEOP LH-2004 protocol; and median 5.55 (IQR 4.09–7.93) years of follow-up. CHL progressed or relapsed in 37 patients (27.8%), the median FFP was 0.89 years (IQR = 0.59–1.54), and 14 patients (10.5%) died. The FPR (final prognostic rank) model associates the biological HLA-G SNP 3027C/A (numerical point assigned (pt) = 1) and absolute neutrophil count (>8 × 109/L, pt = 2) as variables with the TG (TG3, pt = 3). Results of FPR score analyses for FFP suggested that FPR model (Kaplan–Meier curves, log-rank test for trends) was better than the TG model. At diagnosis, high-risk patients classified at FPR rank 4 and 5 identified 18/22 patients who relapse during the follow-up.

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BCL2 Expression Correlates with Refractory and Relapsed Classic Hodgkin Lymphoma. Its Blokeadge As a Promising Directed-Therapy

Blood ◽

10.1182/blood-2019-124452 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5282-5282

Author(s):

Angelica Gamboa-Cedeño ◽

Cristaldo Nancy ◽

Victoria Otero ◽

Natalia Paola Schutz ◽

Dorotea Fantl ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cell Lines ◽

Target Gene ◽

Rank Test ◽

First Line ◽

Log Rank Test ◽

Classic Hodgkin Lymphoma ◽

Nfkb Pathway ◽

Relapsed Disease ◽

Bcl2 Expression

Classic Hodgkin Lymphoma (cHL) is a germinal center derived lymphoma with 8,500-9,000 new cases/year diagnosed in the US. Despite 90% stage I cHL patients can respond to current systemic therapy, this drops to 60%, when diagnosed in advanced stages. Furthermore, 20-30% of diagnosed patients, would be refractory or would relapse and have a poor prognosis. Refractory and relapsed disease (RRD) is currently the challenge when treating cHL patients. There is no specific therapy to offer rather than rescue chemotherapy schemes, which fails in 50% of the cases and associates with high risk severe toxicity. This highlights the need to deeper understand the cHL molecular biology, the screening for molecular markers suitable to identify the risk of refractory and relapse disease and specific therapeutic directed-targets. We have previously reported that the alternative NFkB pathway, mediated by Rel-B and NIK (NFkB Inducing Kinase), plays an important role in cHL survival. Its constitutive activation sustains high BCL2 expression levels and seems to be involved in the RRD. BCL2 was found as a specific Rel-B target gene in cHL cells by ChIP-Seq (Chromatin Immunoprecipitation sequencing) and expression arrays. BCL2 exogenous expression was enough to partially rescue the death induce in cHL cells, which highlight the relevance of this alternative NFkB pathway target gene. Since the BCL2 data was obtained in human cHL cell lines established from patients with refractory and relapsed disease, we decided to analyze whether mediators of this pathway and BCL2 could be useful as prognosis markers and would represent potential targetable factors in both refractory and relapsed disease. We analyzed NIK and BCL2 citoplasm expression in Hodgkin Reed-Sternberg cells (HRS) in the lymph node biopsies of 113 cHL naïve of therapy patients by inmunohistochemistry [52 female Md age and (range) 36 (6-88), 61 male 40.7 (9-78)]. The follow-up period range from 6 to 136 months. The univariate analysis showed no correlation between NIK or BCL2 expression and the prognosis clinical and pathological parameters, including the PET Scan indicated at the end of the first line treatment, neither the molecular markers routinely assayed. The statistical significance was maintained in multivariate analysis (Logistic and Cox Regression p=0.01). NIK expression did not associate with prognosis but the BCL2 expression level correlated with lack of response to conventional therapy and both early and late disease progression. The survival analysis, using the Kaplan-Meir curves, showed that patients with ≥60% positive HRS cells had a shorter disease-free survival (DFS) [Log Rank Test (Mantel Cox) p=0.002] and a reduced overall survival (OS) [Log Rank Test (Mantel Cox) p=0.02]. L1236, U-H01, KM-H2, SUPDH1 and L540, human cHL cell lines that express BCL2 protein, were sensitive to venetoclax, a specific BCL2 inhibitor. The drug induced a cell cycle arrest in S-Phase when treated with 1uM each 24 hours during 10 days, as compared to wild type cells and cells treated with the vehicle. In summary, we found that the alternative NFkB pathway plays a role in the refractory and relapsed classic Hodgkin Lymphoma disease, being BCL2 one of its key downstream target genes. BCL2 can be used as a prognosis marker determined by routine immunohistochemistry at diagnosis of the primary disease. BCL2 expression correlated with refractory disease to first line conventional therapy and disease progression. Based on the venetoclax effect in cHL cell lines we believe BCL2 directed-therapy in cHL should be considered in the subgroup of cHL patients that express this protein in ≥60% HRS cells in the lymph node biopsy performed at diagnosis. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: venetoclax used to specifically block BCL2.

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A prognostic miRNA based signature in early-stage HER2-positive breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12600 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12600-e12600

Author(s):

Anna Adam-Artigues ◽

Miguel Angel Beltran ◽

Juan Antonio Carbonell-Asins ◽

Sheila Zuñiga ◽

Santiago Moragon ◽

...

Keyword(s):

Systemic Treatment ◽

Early Stage ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Risk Groups ◽

Low Risk ◽

Functional Enrichment ◽

Rank Test ◽

Prognostic Signature ◽

Log Rank Test

e12600 Background: In early-stage HER2+ breast cancer (BC), escalation or de-escalation of systemic treatment is an unmet need. Integration of promising biomarkers into risk scoring will further help progressing in the field. We aim to develop a prognostic signature that integrates two miRNAs (A and B) and quantitative and qualitative clinical variables in patients diagnosed with HER2+ BC. Methods: This study was conducted in a retrospective cohort of 45 HER2+ BC patients. Patients received standard treatment for localized disease. We calculated a prognostic signature for disease-free survival (DFS) using principal components analysis for mixed data combining clinicopathological data (Ki67 and axillary lymph node [pN0, pN1, pN2, pN3]) and expression of two microRNAs (we used mir-16 as housekeeping). Multiple DFS prognostic signatures were calculated and goodness of fit was evaluated by means of Akaike’s Information Criterion (AIC) to perform Cox model selection. Signature was then dichotomized into “high risk” and “low risk” using maximally selected Log-Rank statistics by Hothorn and Lausen, as method for optimal cut-off. Kaplan-Meier curves, Log-Rank test and Breslow test were used to ascertain statistical differences in the probability of DFS between high and low risk groups. MiRNA targeted genes were selected and used to perform functional enrichment analysis with the KEGG pathway database. To select significant terms/pathways, p-values were adjusted by the Benjamini-Hochberg method (p < 0.05). Results: MiR-A and miR-B expression was higher in primary tumor of patients who relapse compared to those free of disease after treatment (p = 0.018 and 0.004, respectively). Both miRNAs were strongly correlated (r = 0.84). This signature was significantly associated with relapse of the disease (HR 1.72; CI 95%: 1.243–2.382; p < 0.01, AIC = 114.02). The optimal cut-off of this score was obtained and patients were classified into high and low risk groups. Median DFS of the high-risk was 44 months while it has been not reached yet across the low risk after a median follow-up of 67 months (HR 8.39; p = 0.005, AIC = 111.784). Significant differences in survival between both groups were found (log rank test p < 0.001; Breslow test p = 0.002). miR-A and miR-B functional enrichment analysis returned 55 significant pathways. Interestingly, P53 pathway, apoptosis and cell cycle which are closely related to tumorigenesis and treatment response, were in the top 5 enriched pathways. Conclusions: Both miRNAs included in this signature are related to important biological pathways associated to BC progression. Our new prognostic signature identifies patients with early-stage, HER2+ BC who might be candidates for escalated or de-escalated systemic treatment. This signature was able to classify patients for DFS in high or low risk groups at the moment of BC diagnosis. Further investigations to validate the value of this new signature are on-going.

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High Resolution Array-CGH Provides New Insights Into the Prognosis of Chronic Lymphocytic Leukemia (CLL): Is 8p Loss Worse Than 17p Loss?.

Blood ◽

10.1182/blood.v114.22.2339.2339 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2339-2339

Author(s):

Andrea Rinaldi ◽

Michael Mian ◽

Davide Rossi ◽

Francesco Forconi ◽

Clara Deambrogi ◽

...

Keyword(s):

Cox Regression ◽

Clinical Course ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Lymphocytic Leukemia ◽

Rank Test ◽

Western World ◽

Clinical Parameters ◽

Log Rank Test ◽

The Impact

Abstract Abstract 2339 Poster Board II-316 BACKGROUND: CLL, the most common adult-onset leukemia in the Western world, has a heterogeneous clinical course. Many advances have led to a better understanding of its pathogenesis and to improvements in treatment strategies, but striking solutions are still missing. We conducted a study to evaluate the impact of genomic aberrations on the clinical course. METHODS: From January 1980 to May 2008, 395 frozen samples of CLL patients, were prospectively collected in four centers. Extracted DNA was analyzed with Affymetrix Human Mapping 6.0 arrays. Normal matched DNA was analyzed for one fourth of the cases. Correlations between minimal common regions (MCR) and clinical parameters were evaluated with the Fisherôs-exact test and their impact on OS with the log-rank test. A p-value after Bonferroni multiple test correction (MTC) (p-adj.) <0.05 was considered as statistically significant. Up to now 266 samples have been analyzed. RESULTS: Analysis of the clinical parameters (CPs) and known risk factors (Rai/Binet, age, doubling time, LDH, beta2, IGVH status, p53 mutations, telomere length, CD38, 11q, 17p) was consistent to previous published series. ZAP70 did not affect the clinical course, likely due inter-laboratories variability. After a median follow up of 53 months, 143/239 (60%) of the patients have started therapy and 63/261 (24%) died. 5-yr OS was 82%. Fisher test between the MCRs and CPs revealed an inverse relation between the presence of trisomy 12 by FISH and del13q14.3, an association between del17p and losses of 8p regions and between CD38 and 12q gain. Before MTC, 46 MCRs had a significant impact on OS and 67. After MTC, 3 regions maintained their role: 8p22 loss (38/248, 15%, p-adj.=0.002, median OS: 26 months vs. 48), 17p13.3-11.2 loss (20/248, 8%, p-adj.=0.001; median OS: 10 months vs. 48). In univariate analysis, the log-rank test among pts with 8p-/17p- (8/248, 3%), 8p- (30/248, 12%), 17p- (12/248, 5%), wild type (198/248, 80%) was statistically significant (p<0.001; see figure). Importantly, none of the analyzed clinical and biological parameters was associated with this aberration. CONCLUSIONS: Loss of 8p22 designated a CLL subgroup with a worse outcome among all patients and in the subset with 17p loss. Our data suggested that this aberration might constitute an independent prognostic factor to be evaluated in independent studies. Results, including a Cox regression model, will be presented on all 395 cases. Disclosures: No relevant conflicts of interest to declare.

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PET -CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Preliminary Results in 193 Patients

Blood ◽

10.1182/blood.v118.21.1619.1619 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1619-1619 ◽

Cited By ~ 1

Author(s):

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Virginia Prates ◽

Miguel A Pavlovsky ◽

Lucia Zoppegno ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Progressive Disease ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Cell Transplant ◽

Bulky Disease ◽

Radio Therapy ◽

Anatomic Reduction ◽

Pet Ct

Abstract Abstract 1619 Background: Positron emission tomography using 18F-fluoro-2-deoxy-d-glucose (FDG-PET-CT) is an important tool for treatment response assessment in Hodgkin Lymphoma (HL) treated with ABVD. It can predict response and overall outcome. The negative predictive value for PET-CT in patients (pts.) with HL is 90–94%. New recommendations define complete remission (CR) for HL as the lack of signs and symptoms of lymphoma with a negative PET-CT. OBJECTIVES: Reduce therapy in pts. who achieve early CR with negative PET-CT. Intensify treatment, only in pts. with positive PET-CT after 3 cycles of ABVD. Achieve CR, event free survival (EFS) and overall survival (OS), as good as in our historical control, when we used 3 or 6 cycles of ABVD plus involved field radio therapy (IFRT) in all pts.(LH-96) PATIENTS AND METHOD: Since October 2005, 200 newly diagnosed pts. with HL have been included in a prospective multicenter clinical trial (LH-05) All pts. received 3 cycles of ABVD and were then evaluated with a PET-CT (PET-CT +3) Pts. with a negative PET-CT+3 and absence of other signs or symptoms of lymphoma were considered in CR and received no further therapy. Pts with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions were considered in partial response (PR) and completed 6 cycles of ABVD and IFRT on PET-CT positive areas. Pts with less than PR received high doses of chemotherapy and an autologous stem cell transplant (ASCT). All pts were re-evaluated at the end of treatment with a new PET CT. One hundred and ninety three pts. have been evaluated. The median age at diagnosis was 29 years. One hundred and twenty five (65%) had localized stage (I-II) non bulky and 68 (35%) presented with advanced stage (III-IV), or bulky disease, 33 (17%) had bulky disease. RESULTS: One hundred and forty-eight (77%) achieved CR with negative PET-CT + 3. Forty-five (21%) were PET-CT+3 positive, 5 showed progressive disease. The other 40 pts. were in PR and completed a total of 6 ABVD + IFRT in PET-CT positive areas. Twenty eight achieved CR and 12 persisted with hypermetabolic lesions. Three died of progressive disease. After finishing planned treatment 178 pts. (92%) were in CR. With a median follow up of 39 months the EFS and OS at 36 months is 80% and 97% respectively. Patients with negative PET-CT +3 have an EFS of 86% compared to 61% for pts. with positive PET-CT+3 (P=0,001). We perform a multivariate analysis for EFS which included age, stage, IPS, bulky disease, extranodal areas and the result of the PET –CT+ 3. This last parameter together with age were the only ones with statistical significance (p=0.001 and 0.046 respectively). When comparing the results LH-05 with LH-96 there is no difference in EFS and OS at 36 months (83% vs. 85% and 97 vs. 96%) but in LH-05 only 23% received 6 cycles of ABVD and IFRT compared to 61% and 100% in LH-96. This reduces the exposure to chemo and radiotherapy. CONCLUSION: With PET-CT adapted therapy after 3 cycles of ABVD, 148 pts.(77%) received only 3 cycles of ABVD as initial therapy with an EFS and OS of 80% and 97% at 36 months. In the Cox regression model, PET-CT at completion of treatment was the most significant factor associated to EFS. In this interim analysis of PET-CT adapted therapy to all stages of HL, treatment with 3 cycles of ABVD can be adequate for pts. with negative PET-CT+3. Continuing with ABVD after a positive PET-CT +3 can be considered insufficient. A longer follow-up and a larger number of pts. are necessary to confirm these results. Disclosures: No relevant conflicts of interest to declare.

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The Effect Of CMV Reactivation On Relapse and Survival In Patients With AML and MDS After Allogeneic Stem Cell Transplant (allo-HCT)

Blood ◽

10.1182/blood.v122.21.4531.4531 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4531-4531

Author(s):

Armin Ghobadi ◽

Amir Hamdi ◽

Piyanuch Kongtim ◽

Denai Milton ◽

Amin Alousi ◽

...

Keyword(s):

Cumulative Incidence ◽

Conflicts Of Interest ◽

Group Differences ◽

Rank Test ◽

Cancer Center ◽

Published Data ◽

Cell Transplant ◽

Transplant Outcomes ◽

Cmv Reactivation ◽

Cmv Antigenemia

Introduction The effect of CMV reactivation after allo-HCT on relapse and overall survival (OS) in patients with acute myeloid leukemia (AML) and myelodysplatic syndrome (MDS) is controversial (Green et al blood 2013, Elmaagacli et al Blood 2011, and Erard et al Hematologica 2006). Methods We retrospectively analyzed the effect of CMV reactivation on OS and cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) in AML and MDS patients older than > 18 years who had received allo-HCT between 2005-2011 and had not died within 30 days of receiving allo-HCT at MD Anderson Cancer Center. The effect of any CMV antigenemia on allo-HCT outcomes was evaluated by comparing any CMV antigenemia with no CMV antigenemia. Because of potential immunomodulatory effect of CMV infection, the effect of prolonged antigenemia (defined as CMV antigenemia with duration more than 12 days, the median duration of antigenemia for the cohort) on transplant outcomes was analyzed by comparing patients with prolonged antigenemia with patients with no CMV antigenemia or CMV antigenemia with ≤ 12 days. All patients underwent surveillance by pp65 antigenemia test. Preemtive therapy was initiated for > 3 pp65 Ag cells/million WBC's. Kaplan-Meier survival curves were used to estimate OS and the log-rank test was used to assess group differences. CIR and NRM were determined using the competing risks method; competing risk for CIR was death and for NRM was relapse. Group differences in CIR and NRM were assessed using Gray's test. Results Table 1 shows baseline characteristics. Comparing R+/D+, R-/D-, R-/D+, and R+/D- groups, the incidence of any CMV antigenemia after HCT was 48%, 16.7%, 13.5%, and 50.9%, respectively (p<0.0001) and the incidence of CMV disease was 1.0%, 1.9%, 2.7%, and 4.5%, respectively (p = 0.05). When any CMV antigenemia was compared with no CMV antigenemia post allo-HCT, CMV reactivation had no effect on OS (p > 0.15) and CIR (p > 0.61) in all cohort as well as AML and MDS subgroups. Comparing any antigenemia vs. no antigenemia, CIR at 3 years was 34.6% vs. 35.2% in all cohort, 36.7% vs. 36.6% in AML patients, and 29.5% vs. 30.0% in MDS patients, respectively. In patients with CMV antigenemia, duration of antigenemia ranged from 1 to 535 days (median 12 days). We then investigated the effect of prolonged CMV antigenemia on transplant outcomes. Patients with CMV antigenemia > 12 days compared with combined group of ≤ 12 days or no CMV antigenemia had a lower cumulative incidence of relapse and a higher NRM, resulting in a similar OS (Fig. 1). Such a difference was seen in AML but not in MDS subgroup. We then investigated the effect of duration of CMV antigenemia in patients with CMV reactivation. Comparing 1-12 days of antigenemia vs. more than 12 days of antigenemia, CIR at 3 years was 41.9% vs. 26.7% (p = 0.003) in all cohort, 45.8% vs. 26.4% (p = 0.001) in AML patients, and 32.1% vs. 27.4% (p = 0.68) in MDS patients, respectively. Conclusion Prolonged CMV antigenemia is associated with decreased relapse in patients with AML, but not in MDS. Lower relapse is offset by increased NRM resulting in no change in OS. In contrast with published data, lower rate of relapse was not found when any antigenemia was compared with no antigenemia. Disclosures: No relevant conflicts of interest to declare.

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Validation of the NCCN-IPI for Diffuse Large B-Cell Lymphoma (DLBCL) in a Nation-Wide Spanish Series of 1885 Patients. the Geltamo-IPI Project

Blood ◽

10.1182/blood.v126.23.3955.3955 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3955-3955

Author(s):

Carlos Montalbán ◽

Antonio Díaz-López ◽

Heidys Garrote Santana ◽

Julián Matias Freue ◽

Lourdes López ◽

...

Keyword(s):

Research Funding ◽

De Novo ◽

International Prognostic Index ◽

Geographical Area ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

Rank Test ◽

Published Data ◽

Pairwise Comparisons

Abstract The development of the NCCN International Prognostic Index (NCCN-IPI) for patients with DLBCL treated in the rituximab era improves discrimination when compared to the original IPI model. The aim of the present study is to validate the results of the NCCN-IPI in a large independent series of patients in a different geographical area. Materials & Methods. This nation-wide retrospective study includes 2156 patients with de novo DLBCL diagnosed in 20 (mostly) large academic Spanish centers within the Grupo Español de Linfomas y Transplante de Médula Osea (GELTAMO) network between 1998 to July 2014. Patients had to be ≥ 18 years-old, treated with rituximab plus chemotherapy (R-CHOP or variants and also more intense treatments) and a minimum of 1 year of follow-up; all histological subtypes of DLBCL and primary extranodal cases were acceptable, with the only exclusion of primary testicular or CNS sites. In the whole series the scoring of the IPI and NCCN-IPI indexes were used and 5-year Overall Survival (5y-OS) estimated with the Kaplan-Meier method and compared with the log-rank test. Results. Debugging the database resulted in a final working series that included 1885 patients. The demographics of the series were comparable to the NCCN series: NCCN/GELTAMO male gender(%) 54 vs 50.4, Age(y) 57 vs 60, LDH>1(%) 50 vs 54.7, Ann Arbor stage III-IV (%) 59 vs 62.5, ECOG PS≥2(%) 11 vs 30, extranodal disease(%) 36 vs 40.7. The IPI scoring (1760 patients) significantly separated the four risk groups, low (LR, 33.6% of the patients), low/intermediate (LI, 22.7%), intermediate/high (HI, 25.1%) and high (HR, 18.6%) with significantly different (p<0.001 in the global and pairwise comparisons) 5y-OS 5 (88, 77, 68 and 51%, respectively) (Figure 1). The NCCN-IPI (1773 patients) also significantly (p<0.001 in the global and pairwise comparisons) separated the four risk groups (L 12,7%, LI 34.5%, HI 37% and H 15.8%) with 5y-OS (%) of 93, 84, 67 and 49, respectively (Figure 2), comparably to the published data (Table 1). Conclusions. NCCN-IPI for the prognosis of DLBC lymphoma treated with chemo-immunotherapy has been validated in a large independent Spanish series. However, in our population the NCCN-IPI is not more powerful than the IPI for predicting survival. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures López-Guillermo: Roche, Celgene, Mundipharma, Gilead, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dlouhi:Gilead: Equity Ownership. Martín García:Servier, Gilead: Consultancy. Sancho:CELLTRION, Inc.: Research Funding.

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A moncentric review of targeted therapy on overall survival in metastatic renal clear cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15593 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15593-e15593

Author(s):

Melanie Tadj ◽

Valentin Arnoux ◽

Mireille Mousseau ◽

Jean Luc Descotes ◽

Jean-Louis Quesada ◽

...

Keyword(s):

Overall Survival ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Risk Groups ◽

Renal Clear Cell Carcinoma ◽

Rank Test ◽

First Line ◽

Log Rank Test ◽

Targeted Treatments ◽

Practice Methods

e15593 Background: Anti-angiogenic treatment had radically modified therapeutic strategy in metastatic renal cell carcinoma (mRCC). This study is aimed to determine the overall survival (OS) improvement in clinical practice. Methods: Retrospective, monocentric and non-interventional study in mRCC diagnosed since 2000 with 2 cohorts of patients determined according to the first line treatment (targeted therapy or others treatment). Results: Between 1 January 2000 and 31 December 2010, 98 patients were included. The 2 cohorts were balanced with regard to baseline disease and demographic characteristics in particular for prognosis profiles distribution. As first line, 58 patients received targeted therapy whose 21% were treated by bevacizumab, 71% by sunitinib and 8% by temsirolimus. In non-targeted therapy cohort (n=40), 37.5% were treated by cytokines, 15% by cytotoxic chemotherapy or hormonal therapy. Patients treated with targeted therapy had a significantly longer median OS (30 months versus 13 months; p<.003, log-rank test). The Hazard Ratio (HR) of death at 3 years was 0.53 (95% Confidence Interval, 0.33-0.85; p=.008, log-rank test). When adjusted to the prognosis profile, the HR of death was 0.43 (95%CI, 0.27-0.71). Conclusions: This retrospective study demonstrated the improvement of OS due to targeted treatments, for all prognostic risk groups. This result supported the complete change of care of mRCC patients with extension of therapeutic indications and efficient therapeutic lines.

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Immune Score Closely Associated With Tumor Microenvironment as A Prognostic Factor in Lung Adenocarcinoma

10.21203/rs.3.rs-75595/v1 ◽

2020 ◽

Author(s):

Na Li ◽

Xiaoling Chen ◽

Chang Liu ◽

Yong Feng ◽

Xiaoqiang Sun ◽

...

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Prognostic Factor ◽

Tumor Microenvironment ◽

Lung Adenocarcinoma ◽

Prognostic Significance ◽

Risk Groups ◽

Rank Test ◽

Log Rank Test ◽

Immune Score

Abstract Background: The tumor microenvironment plays a vital role in tumor biology and has recently attracted widespread attention. However, the prognostic significance of integrated immune scores in lung adenocarcinoma has not yet been identified. This study aimed to systematically estimate the association between immune scores and prognosis and develop a clinical nomogram to predict the survival of patients with lung adenocarcinoma. This study also systematically explored the underlying prognostic factors of the immune score in lung adenocarcinoma.Methods: Public datasets for lung adenocarcinoma was acquired from The Cancer Genome Atlas data portal. The immune score of each sample was calculated using the ESTIMATE algorithm. Univariate and multivariate Cox regression analyses identified several significant prognostic factors and further developed a prognostic nomogram. The C-index, calibration curve, and ROC curve were used to evaluate the predictive accuracy and discriminative ability of the resultant nomogram. Results: We found that patients with higher immune scores had a better prognosis (log rank test p = 0.0004). The nomogram that integrated the immune score could effectively stratify high-risk LUAD patients in terms of clinical response. Patients in the high-risk groups usually had a worse prognosis (log rank test p < 0.0001) and higher mortality. The mortality rate in high and low risk groups was 42.67% and 26.37%, respectively (p < 0.0001). In addition, correlation analysis showed that the immune score was significantly dependent on the mRNA expression of immunotherapy-associated biomarkers (PD-1, PD-L1, and LAG3) as well as on the presence of certain immune cell subtypes, but had no correlation with tumor mutation burden.Conclusion: The immune score is a prognostic factor in lung adenocarcinoma. The nomogram with an integrated immune score can effectively predict the survival of patients with lung adenocarcinoma. The mechanism by which the immune score estimates the prognosis of patients with lung adenocarcinoma is related to the tumor immune microenvironment.

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