Excellent Outcome of Nodular Lymphocyte Predominant Hodgkin Lymphoma in the Eastern Province of Saudi Arabia. a Real-World Case Series of 49 Consecutive Patients Treated at a Referral Center from 2006 to 2017

Abstract Background Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of HL for which optimal treatment is controversial. We retrospectively reviewed the files of patients with NLPHL diagnosed and followed up at our institution and describe clinical characteristics and outcome and explore prognostic factors for progression-free survival (PFS) and overall survival (OS). Methods We included consecutive patients diagnosed with NLPHL and followed at King Fahad Specialist Hospital, Damamm (KFSH-D), a referral center for the Eastern Province of Saudi Arabia. Primary aim of this study was to determine clinical outcomes (PFS and OS) according to treatment strategy, i.e. radiotherapy (+/- Rituximab) (RT) only, chemotherapy (+/- Rituximab) (CT), combined modality (+/- Rituximab) (CMT), Rituximab monotherapy (R), and active surveillance (AS). Secondary aim was an exploratory analysis of candidate prognostic factors for PFS and OS. PFS was defined as time (months) from date of diagnosis to disease progression or death from any cause. Event time distributions were estimated using the method of Kaplan-Meier and groups were compared using the log-rank test. We used univariable and multivariable PFS analyses for candidate prognostic factors. Results From 1/2006 to 12/2017 data on 49 patients treated at KFSH-D, aged 16 years (y) or older, with a diagnosis of NLPHL and with sufficient treatment and follow-up (F/U) were analyzed. Median age at diagnosis was 29y (range, 16-56), 76% were male. Histology was typical in 86% (n=42), variant in 8% (n=4), and with transformed histology at diagnosis in 6% (n=3) of cases. Disease characteristics: 63% (n=31) of patients were stage I/II and 37% (n=18) stage III/IV, B-symptoms 12%, extranodal disease 10%, splenic involvement 8%, bulky disease (≥5 cm) 12%, and bone marrow involvement 4% of patients. The German Hodgkin Study Group (GHSG) score was intermediate-risk and high-risk in 53% (n=26) and 24% (n=12) of patients, respectively. Management strategy (MS), depending on physician's preference, was RT (16%, n=8), CT (43%, n=21), CMT (27%, n=13), R (6%, n=3), and AS (8%, n=4). For patients induced with chemotherapy +/- RT, ABVD-like (+/- Rituximab) (n=25) or CHOP (+/- Rituximab) (n=9) were used in all cases. The overall response rate (ORR) for 45 patients who received treatment was 91% (complete responses (CR), 69%), 98% ORR when cases with transformed histology at diagnosis were excluded. Median F/U was 36 months (m), (range, 8-127). Overall, outcome was excellent, with 3- and 5-y PFS estimates of 80% and 75%, respectively (Figure). Overall survival was 100% with no deaths observed (Figure). The current PFS is 98%. Transformation at relapse/progression was observed in 2 patients at 36m and 45m, respectively, and remain disease free at 24m and 35m, respectively, following salvage treatment and auto-SCT. The 5-y cumulative risk of transformation (excluding cases with transformed histology at diagnosis) was 6%. Two secondary cancers were observed. Exploratory univariate analysis revealed high-risk GHLG score (P=0.001), bulky disease (P=0.001), splenic involvement (P=0.01), transformed histology at diagnosis (P=0.02), and non-RT MS (P=0.001) as risk factors for shorter PFS. In the final multivariate model, the GHLG score (P=0.01) and non-RT MS (P=0.004) were the only a risk factor for shorter PFS. In pairwise comparison, excluding patients with transformed histology at diagnosis and patients on AS, for patients with stage I/II disease, RT-based therapy was associated with improved 5-y PFS rates compared to CT-based therapy, (P = 0.02). For patients with stage III/IV disease 5-year PFS rates did not differ between RT-based and CT-based therapy (P= 0.4). For patients treated with CT, ABVD +/- Rituximab (n=13) vs CHOP +/- Rituximab (n=8) induction produced similar PFS rates at 5-years (P=0.9). Conclusion In this single center retrospective study, NLPHL had an excellent outcome. MS had an impact on PFS but not OS. High-risk GHLG score and omission of upfront RT were adversely prognostic factors for PFS. Large prospective trials are warranted to determine the optimal treatment approach for this rare B-cell lymphoma. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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Excellent Outcome for Pediatric Patients with High Risk Hodgkin Lymphoma with Brentuximab Vedotin and Risk Adapted Residual Node Radiation

SSRN Electronic Journal ◽

10.2139/ssrn.3716895 ◽

2020 ◽

Author(s):

Monika Metzger ◽

Michael P. Link ◽

Amy L. Billett ◽

Jamie Flerlage ◽

John T. Lucas Jr. ◽

...

Keyword(s):

High Risk ◽

Hodgkin Lymphoma ◽

Pediatric Patients ◽

Brentuximab Vedotin ◽

Excellent Outcome

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Knowledge and Awareness about Colorectal Cancer and Its Screening Guidelines among Doctors in Al Ahsa, Eastern Province, Kingdom of Saudi Arabia

Global Journal of Health Science ◽

10.5539/gjhs.v9n6p145 ◽

2016 ◽

Vol 9 (6) ◽

pp. 145

Author(s):

Bathula Surendra ◽

Muhammad Mujtaba Hashir ◽

Fahad Salman Al Harbi ◽

Mohammed Jassim Al Nuwaysir ◽

Khalid Majed Al Khaldi ◽

...

Keyword(s):

Colorectal Cancer ◽

Saudi Arabia ◽

High Risk ◽

Public Health Problem ◽

Screening Tests ◽

High Risk Population ◽

Major Public Health Problem ◽

Eastern Province ◽

Risk Population ◽

Screening Guidelines

INTRODUCTION: Cancer is a major public health problem. Worldwide, colorectal cancer (CRC) is a leading cause of deaths due to cancer in both men and women. Among, Saudi men, CRC is the most common malignancy while it is the third most common among Saudi women. Over, two decades the incidence and deaths due to CRC have been steadily increasing in Saudi Arabia. Regular and timely screening has the potential in reducing the incidence and deaths due to colorectal cancer. The present study is conducted to evaluate the knowledge and awareness about colorectal cancer and its screening among the doctors.OBJECTIVES: To measure the frequency of knowledge and awareness about colorectal cancer and its screening guidelines among doctors in Al-Ahssa.METHODS: A questionnaire based survey of the doctors (Specialists & residents), working in different hospitals and primary health centers under the Ministry of Health in Al Ahssa region, Eastern province, KSA. Knowledge and awareness about colorectal cancer and its screening among the doctors is evaluated.RESULTS: Over 80% of the doctors knew, screening reduces deaths due to CRC. Only 60% were aware about the risk factors and less than 50% knew the clinical features of CRC. About 60% doctors agreed Colonoscopy is gold standard screening test. While, less than 60% knew the ideal age to initiate screening and the actual interval of screening tests in the standard risk and high-risk population. Fewer than 25% doctors were aware about the American cancer society recommended screening guidelines. Majority of the doctors expressed keen interest to know and receive information about CRC and its screening guidelines. CONCLUSIONS: Regular and timely screening reduces deaths due to CRC. There is a need for improving knowledge and awareness of doctors about CRC and its screening. Awareness among the doctors improves uptake of screening by the general and high-risk population.

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PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽

10.1182/blood.v116.21.1772.1772 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1772-1772

Author(s):

Santiago Pavlovsky ◽

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Miguel Pavlovsky ◽

Virginia Prates ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Progressive Disease ◽

Cell Transplant ◽

Advanced Stage ◽

Event Free Survival ◽

Bulky Disease ◽

Free Survival ◽

Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

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Chronic Lymphocytic Leukemia: Evaluation of Cytogenetic Markers as Prognostic Factors

Blood ◽

10.1182/blood.v116.21.4860.4860 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4860-4860

Author(s):

Jose Carda ◽

Patricia Sousa ◽

Patricia Olim ◽

Emília Magalhães ◽

Luis Rito ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Retrospective Study ◽

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Progressive Disease ◽

Risk Group ◽

Staging System ◽

Lymphocytic Leukemia ◽

Intermediate Risk

Abstract Abstract 4860 Backgroud: Chronic lymphocytic leukemia (CLL) is one of the most frequent chronic lymphoproliferative disorders in Europe. It is characterized by persistent monoclonal lymphocitosis with localized or generalized lymphadenopathy. Despite the initial clinical presentation, it has a heterogeneous natural history, with the majority of patients living 10–12 years, but with some patients dying rapidly, within 2–3 years of diagnosis. Beside clinical prognostic factors, novel cytogenetic markers are recognized to be useful in predicting disease free and overall survival in CLL. AIMS: In a retrospective study throughout 10 years (1999-2009), we analyzed the clinical and biological presentation and compared the evolution and survival of patients with B-CLL using different cytogenetic markers. METHODS: We identified 112 cases (63 males and 49 females) of B-CLL with cytogenetic study by fluorescence in situ hybridization (FISH). RESULTS: Amongst 112 patients, the male to female (M/F) ratio was 1.3:1 and the median age was 70 (43-96) years. At diagnosis, the median lymphocyte count was 15.5 G/L (5.4-173). Fifty five patients (49%) had lymphadenopathies and seventeen (15%) had splenomegaly and/or hepatomegaly at presentation. By the revised Rai staging system seventy (63%) patients were included in low risk group, thirty (27%) in intermediate risk group and twelve (10%) in high risk group. The expression of ZAP-70 and CD38 by flow citometry was performed in 75 patients and revealed 13 (17%) patients CD38+ and 12 (16%) ZAP70+. The study of chromosomal aberrations with FISH showed thirty six patients (32%) with no abnormality, thirty six (32%) with isolated 13q deletion, fifteen (14%) with 12 trisomy, twelve (11%) with 11q deletion and thirteen (11%) with 17p deletion. Forty (36%) patients showed progressive disease in a median time of sixteen months (0-120), thirteen with 13qdel, seven with 17pdel and five with 12 trisomy. After treatment two patients showed progressive disease, six maintain a stable disease and thirty two obtain a remission, nine in complete remission. The Overall Survival (OS) at ten years was 70%. By the revised Rai staging system the OS at ten years was 80% for low risk, 70% for intermediate risk and all the high risk patients died during follow up. The OS at five years for the del13q-, 12 trisomy, del11q- and del17p- was 90%, 88%, 58% and 60%, respectively. SUMMARY: Chronic lymphocytic leukemia is currently considered a chronic disorder with a favourable outcome, but with a variable evolution to progressive disease. This retrospective study allowed the characterization of patient with CLL in our department and the acknowledgement that our results are quite similar to the published data. Disclosures: No relevant conflicts of interest to declare.

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Hodgkin Lymphoma: 20 Years Experience From a Single Brazilian Institution

Blood ◽

10.1182/blood.v118.21.3153.3153 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3153-3153

Author(s):

Camila C.G. Linardi ◽

Luis Fernando Pracchia ◽

Rodrigo Dolphini Velasques ◽

Claudia Bitti Barroso ◽

Valeria Buccheri

Keyword(s):

Prognostic Factors ◽

Hodgkin Lymphoma ◽

Developed Countries ◽

Stage I ◽

Advanced Stage ◽

Bulky Disease ◽

Free Survival ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Abstract 3153 Hodgkin Lymphoma (HL) is characterized by high cure rates. Approximately 90% early stage and 60–70% advanced stage patients have long term disease free survival. In Brazil it is observed that about 60% of patients present with advanced stage, while in developed countries about 40% belong to this group. The aim of this retrospective study was to analyze data of patients with HL from the Oncohematology Unit of University of São Paulo- Medical School and evaluate the event free survival (EFS) and the overall survival (OS) according to clinical stage. We included all consecutive patients diagnosed with HL between January 1991 and June 2010. The collection of data from medical records was done and the following variables at diagnosis were evaluated: age and sex, staging according to Cotswolds modified Ann-Arbor criteria (CS), histological subtype, presence of B symptoms and bulky disease, International Prognostic Index (IPI) according to International Prognostic Factors Project on Advanced Hodgkin's Disease, laboratorial data, and the protocol used in first line therapy. The complete remission (CR) rate, EFS and OS were analyzed in all patients. The survival analysis was estimated by the Kaplan-Meier method and the survival curves were compared by the log-rank test. Differences in CR rates among staging groups were compared using the chi squared test. Overall, 564 HL patients were identified; thirteen did not have adequate information about clinical staging and were excluded from the analysis. The median age, at diagnosis, of the remaining 551 patients was 28 (12–83) and 54.3% were male. Histological subtypes lymphocyte rich classical HL, nodular sclerosis, mixed cellularity and lymphocyte depletion were found in 3.6%, 51.4%, 24.2% and 5.6% cases, respectively, and 11.8% patients were diagnosed as HL classic not classifiable otherwise. Nodular lymphocyte predominance was observed in 3.3% cases. Stage I, II, III and IV were found in 42 (7.6%), 208 (37.7%), 145 (26.3%) e 156 (28.3%) patients, respectively. B symptoms and bulky disease were present in 65.5%and 58.8% patients, respectively. After staging the patients were divided in three groups: group 1 -CS I/II, without B symptoms nor bulky disease= 62 (11.25%) patients, group 2 -CS I/ II, with B symptoms and/or bulky disease=188 (34.12%) patients and group 3- CS III/ IV= 301 (54.62%) patients. IPI high risk score was recognized in 63.9% patients of group 3. Only 1.5% of patients were treated with exclusive radiotherapy. Of the patients that were treated with chemotherapy, 4.9% were treated with MOPP, 23.1% with MOPPABV, 70.5% with ABVD and 1.5% with other types of chemotherapy. The median follow-up of the entire cohort was 59.6 months (0–258.8 months) and 88.3% (CI 95%: 85.2%-91.1%) were in CR at the end of treatment (CS I: 100%, CS II: 90.6% CS III: 84.6% and CS IV: 85.3%; p=0.03) (group 1: 98.2%, group 2: 90.2% and group 3: 84.9%; p=0.012). The 5-year EFS rate was 69.2% (CS I: 84.8%; CS II: 77.8%; CS III: 64.5%, CS IV: 56%; p=0.0008) (group 1: 88%, group 2: 76% and group 3: 60.3%; p=0.0002) (Figures 1 and 2). The 5-year OS rate was 86.44% (CS I: 90.3%, CS II: 94.6%, CS III: 87.6%, CS IV: 71.4%; p<0.0001) (group 1: 98.3%, group 2: 92.6% and group 3: 79, 6%; p=0.0003).Figure 1Figure 1. Figure 2Figure 2. We found that there were more advanced stage patients (stage III/IV) in comparison to developed countries, however, patients classified as stage I/II without poor prognostic factors, like B symptoms and/or bulky disease, showed high rates of CR, EFS and OS. These data suggest that there is a need to enhance early diagnosis in Brazilian patients, in order to detect less advanced stage patients due to late diagnosis. Disclosures: No relevant conflicts of interest to declare.

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Interim Absolute Lymphocyte Count (ALC) As a Predictor of Survival in Hodgkin Lymphoma

Blood ◽

10.1182/blood.v126.23.2640.2640 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2640-2640

Author(s):

Tarsheen K. Sethi ◽

Van T Nguyen ◽

David S Morgan ◽

John P. Greer ◽

Nishitha M Reddy

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Lymphocyte Count ◽

Absolute Lymphocyte Count ◽

Disease Stage ◽

Predictive Score ◽

Advanced Stage ◽

Bulky Disease ◽

Nodular Sclerosis

Abstract Introduction: Patients with Hodgkin lymphoma (HL) have excellent response to current chemotherapy, however, up to 20% may have relapsed/refractory disease. Lymphocytopenia at diagnosis has been found to be predictive of survival in patients with advanced stage HL. An ALC of <600/μlat diagnosis as part of the Hasenclever predictive score is associated with a poorer prognosis. Furthermore, lymphocyte count at the time of apheresis and at day 15 after autologous SCT has been found to be predictive of survival in patients of HL. ALC is considered a surrogate indicator for the tumor microenvironment as well as immune recovery post treatment. There are no large studies evaluating the clinical significance of ALC recovery in patients with HL during initial chemotherapy treatment. In this study, we evaluated the role of lymphocyte recovery during and after standard chemotherapy in patients with HL. Patients and Methods: We analyzed 183 patients with Classical Hodgkin lymphoma treated at our institution between 1996 and 2014 following IRB approval. Complete data was available for 115 patients. We evaluated the absolute lymphocyte count at diagnosis, interim staging (after 2 cycles, Òinterim ALCÓ), at time of completion of chemotherapy and at 6 weeks and 3 months post completion of chemotherapy. Patients were categorized into two groups based on ALC where lymphocytopenia was defined as an ALC of <1x103/µl for adults based on standard criteria. Differences between the two groups were analyzed using Chi- square and t -Student tests. Statistical significance was set at P <0.05. Kaplan Meier method was used to calculate the Progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. Statistical analysis was performed using SPSS.22 software. Results: The median age of patients was 31 years (yrs.) (range: 17-76 yrs.) and 53% of patients were male. 100% patients had an ECOG status of 0-1. 48% patients presented with B symptoms, 42% had advanced stage disease (Stage III and IV) and 22% had bulky disease (defined as a mass > 10 cm or mediastinal mass >1/3 of diameter of thorax at T5-T6). In terms of histology, 68% patients had classical nodular sclerosis HL, 19% syncytial variant of nodular sclerosis HL, 8% mixed cellularity HL and 5% Classical HL (NOS). 90% patients received ABVD as their initial chemotherapy, 2% received Stanford V and 1% received MOPP. The remaining patients were treated on a clinical trial. In the analysis of the 115 patients for whom the lymphocyte data was available, at a median follow up of 40 months, 57% in the ALC <1x103/µl group versus 66% in the ALC >1x103/µlgroup had not progressed. The median overall survival was not reached in the two groups. In the multivariate analysis, for PFS, interim ALC predicted survival independent of the interim staging response. The ALC at the time of interim staging scan (interim ALC) was associated with a significantly superior PFS in the group with ALC>1x103/µl(HR=4.16, 95% CI 2.37 to 7.28, P=0.024). There was no difference in overall survival between the groups (Fig. 1&2,P=0.28). For ALC at other time points, no statistically significant differences in PFS or OS were found in the two groups based on ALC at diagnosis, completion of therapy, six weeks and three months post therapy. Discussion: In summary, our results suggest that for patients across all stages and histopathologic subtypes of classical HL receiving first line chemotherapy, interim ALC >1x103/µl (after 2 cycles) is associated with a superior PFS as compared with ALC <1 x103/µl and this is independent of the interim staging response. This did not translate into a difference in OS. Further studies are underway to determine the role of immune effector cells in the context of newer therapeutic agents. Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Disclosures Reddy: Gilead: Other: Speaker; Seattle Genetics: Consultancy; ImmunoGen: Consultancy; PCYC: Consultancy; Celgene: Consultancy, Research Funding.

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Red Cell Distribution Width (RDW) at Diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL) Is Associated to Higher Mortality and Worse Overall Survival

Blood ◽

10.1182/blood.v128.22.5398.5398 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5398-5398

Author(s):

Leyre Bento ◽

Juan Sarmentero ◽

Ana Ortuño ◽

Marta García-Recio ◽

Bernardo Lopez ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

High Risk ◽

Roc Curves ◽

Red Cell Distribution Width ◽

Red Cell ◽

Cell Distribution ◽

Distribution Width ◽

Ecog Ps

Abstract Red cell distribution width (RDW) is an indicator of the variability in the size of circulating erythrocytes (anisocytosis); different conditions can increase the RDW levels; such as hemolysis, ineffective erythropoiesis and blood transfusions. Recently, different studies have shown an association between increased levels of RDW and inflammation in different diseases, being proposed as a surrogate marker of inflammation and a strong predictor of adverse outcome. The proposed mechanism of this association departs from the finding that Inflammatory cytokines like TNFand IL-6 (part of the classic inflammatory cascade), have been found to inhibit erythropoietin-induced erythrocyte maturation, which is reflected in the RDW increase. Some reports have found a relationship between RDW and mortality related to age or several malignant or non-malignant conditions. However, there is no information about the role of RDW in overall survival (OS) of patients with DLBCL. We aim to evaluate the prognostic role of RDW levels in DLBCL patients at diagnosis. METHODS We retrospectively evaluated 83 patients with DLBCL homogenously treated in frontline with R-CHOP from 2002 to 2013 in the Son Espases University Hospital. To avoid selection bias patients were obtained from Pharmacy and Pathology Departments registries. Main clinical and prognostic factors at diagnosis were obtained from medical records. Cheson criteria were used for response assessment. The RDW was collected from the hemogram at diagnosis. The IBM SPSS STADISTICS program was used for all statistical analyses. PFS (time to progression/relapse) and overall survival (OS) (time to death) were measured from the date of ABVD onset, and were estimated according to the Kaplan-Meier method. We performed the comparisons between those interest variables with the log-rank test. A comparison between categorical variables was made with the chi-square of Fisher's exact test, as appropriate. All reported P-values were two-sided, and statistical significance was defined at P<0.05. For selecting cutoff values in RDW we used ROC curves. RESULTS: Main characteristics of patients were as follows: median age was 62 (20-86) years, 24% had ECOG PS>1, 64% advanced III-IV Ann Arbor (AA) stage, 39% B-symptoms, 51% adjusted-International Prognostic Index (a-IPI) and 39% belong to the high risk (3-5) subgroups of R-IPI Median RDW was 14.6 (11.1-21.1). Using ROC curves we selected the cutoff 14.05 for the death event. We evaluated the association of increased RDW with main prognostic factors at diagnosis. RDW >14.05 at diagnosis was associated with a more advanced age, worse ECOG PS, a more advanced AA stage, higher incidence of B symptoms and IPI>2. However, RDW was not related to disease control in terms of response to therapy (p=0.39) or relapse/progression (p=0.21) rates. Inversely, RDW>14.05 was in fact associated to a higher mortality (47%) compared to only 17% in patients with RDW≤14.05 (p=0.008). Median follow-up was 77 (20-137) months. Univariate survival analysis showed age>60 years (p=0.001), ECOG PS>1 (p=0.036), high risk R-IPI (p=0.005), a higher than 15% reduction in relative dose-intensity (RDI) (p=0.026) and RDW>14.05 (p=0.008) were significantly related to worse OS. By contrast, RDW did not significantly influence progression-free survival (p=0.19). CONCLUSIONS: Higher RDW at diagnosis in this series of DLBCL patients was related with older age, worse ECOG PS and more advanced disease but this was not translated into a worse control of disease in terms of only a small non statistically significant impact in response or PFS. By contrast higher RDW was linked to a significantly higher mortality and worse OS possibly related to a higher proinflammatory basal status and comorbidities. Patients with higher RDW may be at risk of reduction in RDI. These findings could justify including RDW in scores of comorbidities in DLBCL as well as in other malignant and non-malignant conditions. Disclosures No relevant conflicts of interest to declare.

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Development and validation of a prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) from the phase 3 prevail clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5022 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5022-5022

Author(s):

Andrew J. Armstrong ◽

Ping Lin ◽

Celestia S. Higano ◽

Cora N. Sternberg ◽

Guru Sonpavde ◽

...

Keyword(s):

Clinical Trial ◽

Overall Survival ◽

Prognostic Factors ◽

High Risk ◽

Prognostic Model ◽

Risk Groups ◽

Multivariable Model ◽

Training Set ◽

Phase 3 ◽

Testing Set

5022 Background: Prognostic models require updating to reflect contemporary medical practice. In a post hoc analysis of the phase 3 PREVAIL trial (enzalutamide vs placebo), we identified prognostic factors for overall survival (OS) in chemotherapy-naive men with mCRPC. Methods: Patients were randomly divided 2:1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined candidate prognostic factors (including treatment) were analyzed in a multivariable Cox model with stepwise procedures and in a penalized Cox proportional hazards model using the adaptive least absolute shrinkage and selection operator (LASSO) penalty (data cutoff June 1, 2014). A multivariable model predicting OS was developed using the training set; the predictive accuracy was assessed in the testing set using time-dependent area under the curve (tAUC). The testing set was stratified based on risk score tertiles (low, intermediate, high), and OS was analyzed using Kaplan-Meier methodology. Results: Demographics, disease characteristics, and OS were balanced between the training and testing sets; median OS was 32.7 months for both datasets. There were no enzalutamide treatment-prognostic factor interactions (predictors). The final multivariable model included 11 prognostic factors: prostate-specific antigen, treatment, hemoglobin, neutrophil-lymphocyte ratio, liver metastases, time from diagnosis to randomization, lactate dehydrogenase, ≥ 10 bone metastases, pain, albumin, and alkaline phosphatase. The tAUC was 0.74 in the testing set. Median (95% confidence interval [CI]) OS for the low-, intermediate-, and high-risk groups (testing set) were not yet reached (NYR) (NYR–NYR), 34.2 months (31.5–NYR), and 21.1 months (17.5–25.0). The hazard ratios (95% CI) for OS in the low- and intermediate-risk groups vs the high-risk group were 0.20 (0.14–0.29) and 0.40 (0.30–0.53), respectively. Conclusions: Our validated prognostic model incorporates factors routinely collected in chemotherapy-naive men with mCRPC treated with enzalutamide and identifies subsets of men with widely differing survival times. Clinical trial information: NCT01212991.

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R-CHOEP-14 Is Associated with Superior Overall Survival Compared to R-CHOP-21 and R-CHOP-14 in Patients with DLBCL ≤70 Years – a Swedish Lymphoma Registry Population Based Study

Blood ◽

10.1182/blood.v124.21.4427.4427 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4427-4427

Author(s):

Tove Wästerlid ◽

Erzsebet Szekely ◽

Linda Werner Hartman ◽

Mats Jerkeman

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Standard Treatment ◽

Performance Status ◽

Population Based ◽

Disease Stage ◽

Randomised Trials ◽

Bulky Disease ◽

Significant Difference ◽

Intensive Regimen

Abstract Background: The current standard treatment for patients with diffuse large B-cell lymphoma (DLBCL) is Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP). Two large randomised trials have been unable to establish a significant difference in outcome between patients receiving R-CHOP at 21 versus 14 day intervals regardless of age (Cunningham et al Lancet 2013, Delarue et al Lancet 2013). Another means of intensifying R-CHOP is by the addition of etoposide (R-CHOEP-14). As of yet, no randomised study in the rituximab era has been performed specifically evaluating the addition of etoposide. The aim of this study was to compare the chemotherapy regimens used to treat DLBCL in Sweden (R-CHOP-21, R-CHOP-14, R-CHOEP-14) among patients aged ≤70 in terms of overall survival, adjusted for clinical prognostic factors. Methods: The study population was identified through the Swedish Lymphoma Registry (SLR) 2007-2012. Data was analysed using STATA and SPSS. Age was modelled as splines in the multivariable analysis. Results: A total of 1745 patients aged ≤70 were identified in the SLR during the time-frame of this study. Median age was 61 years (range 18-70). Of these, 1331 had received R-CHOP-21 (n=302), R-CHOP-14 (n=872) or R-CHOEP-14 (n=157) and were included in the study. Median follow-up time for surviving patients was 49 months. Three-year overall survival rates were 86.7%, 79.6% and 87.5% for the patients who received R-CHOP-21, R-CHOP-14 and R-CHOEP-14 respectively. There was a significant disparity in the distribution of prognostic factors among patients receiving the various chemotherapy regimens with a lower proportion of patients with elevated serum lactate dehydrogenase (S-LDH), performance status >1, stage III-IV and presence of bulky disease (>10 cm) in the R-CHOP-21 group compared to the other regimens. As expected, the most intensive regimen, R-CHOEP-14 was more frequently given to younger patients (median age 49) with high-risk prognostic features. When adjusting for significant prognostic factors (age, performance status, S-LDH, bulky disease, stage and gender) in a multivariable Cox regression model, R-CHOEP-14 was found to be significantly superior both to R-CHOP-21 (Hazard Ratio (HR): 0.53, Confidence Interval (CI):0.3-0.9, p=0.026) and R-CHOP-14 (HR:0.63, CI:0.4-1.0, p=0.048). No significant difference between R-CHOP-14 and R-CHOP-21 was found (HR: 0.84, CI: 0.6-1.2, p=0.3), consistent with findings from randomised trials performed. Conclusion: In this population based series of DLBCL, the more intensive regimen R-CHOEP-14 was associated with superior overall survival in patients aged up to 70 years, indicating that this may be considered among the standard treatment options for this patient population. R-CHOEP-14 should preferably be compared to R-CHOP-21 in a randomised setting in order to further elucidate which patient groups that benefit the most from treatment intensification. Disclosures No relevant conflicts of interest to declare.

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