Overall survival modeling and association with serum biomarkers in durvalumab-treated patients with head and neck cancer.

6549 Background: Optimal patient selection for immunotherapy remains a challenge as most patients fail to respond. We aim to assess baseline factors for association with long-term survival from durvalumab treatment in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)1,2. Methods: Pooled longitudinal tumor size, survival, and dropout data from four trials (1108: NCT01693562, CONDOR: NCT02319044 , HAWK: NCT02207530, and EAGLE: NCT02369874) involving 467 HNSCC patients were used to develop tumor size-driven hazard models. A panel of 66 serum protein biomarkers at baseline and 4 relevant clinical markers from 346 out of 413 patients treated with durvalumab (all studies except 1108) were initially screened to select a pool of 21 candidate covariates. The criteria for dimensionality reduction comprised correlation strength between biomarkers and pharmacological hypotheses pertaining to a prior analysis3 (inflammation, immunomodulation, tumor burden and angiogenesis). Results: The final tumor model highlighted that high tumor burden, elevated LDH and neutrophil-lymphocyte ratio were associated with faster tumor growth while patients with lower baseline tumor burden had an increase in net tumor shrinkage. For overall survival, the model suggested that high levels of immunomodulators (IL23, Osteocalcin), low inflammation (IL6, NLR), low tumor burden, and low angiogenesis factors (von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1)) were associated with survival benefits for patients treated with durvalumab. Specifically, these patients had baseline serum IL23 > 2.1 pg/mL and Osteocalcin > 32 pg/mL or serum PAI-1 < 229 pg/mL and serum IL6 < 5.4 pg/mL which corresponded to a hazard ratio estimate (HR and 95%CI) of 0.36 (0.27- 0.47), logrank p-value: 2.3x10−14. The median (n, 95%CI) overall survival time for the patients with favorable biomarker profile was 14.6 months (n = 129, 11.2-21.4) vs. 4.4 months (n = 217, 3.6-5.3). Conclusions: Our results corroborate the prior hypothesis highlighting the prognostic value of inflammation, disease burden, tumor angiogenesis, and immunomodulatory factors on the clinical outcomes of HNSCC patients treated with durvalumab3. Collectively, we identified a serum biomarker profile of HNSCC patients with median survival times exceeding 1 year which may potentially be used for patient enrichment following further validation in prospective studies. References: 1Yanan CPT 2017, 2Baverel, 2018 ENA, 3Guo, X, 2019 Asco P6048 Clinical trial information: NCT01693562, NCT02319044, NCT02207530, NCT02369874 .

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Differences in Clinical and Dietary Characteristics, Serum Adipokine Levels, and Metabolomic Profiles between Early- and Late-Onset Gout

Metabolites ◽

10.3390/metabo11060399 ◽

2021 ◽

Vol 11 (6) ◽

pp. 399

Author(s):

Young Sun Suh ◽

Hae Sook Noh ◽

Hyun-Jin Kim ◽

Yun-Hong Cheon ◽

Mingyo Kim ◽

...

Keyword(s):

Early Onset ◽

Late Onset ◽

Clinical Information ◽

Plasminogen Activator Inhibitor ◽

Ultra Performance Liquid Chromatography ◽

Plasminogen Activator Inhibitor 1 ◽

Baseline Serum ◽

Onset Group ◽

Early Onset Group ◽

Pai 1

This study aimed to identify differences in clinical and dietary characteristics, serum adipokine levels, and metabolomic profiles between early- and late-onset gout. Eighty-three men with gout were divided into an early-onset group (n = 38, aged < 40 years) and a late-onset group (n = 45, aged ≥ 40 years). Dietary and clinical information was obtained at baseline. Serum adipokines, including adiponectin, resistin, leptin, and plasminogen activator inhibitor-1 (PAI-1), were quantified by a Luminex multiplex immunoassay. Metabolite expression levels in plasma were measured in 22 representative samples using metabolomics analysis based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Average body mass index, rate of consumption of sugar-sweetened beverages, and serum uric acid levels were significantly higher in the early-onset group (p < 0.05), as was the PAI-I concentration (105.01 ± 42.45 ng/mL vs. 83.76 ± 31.16 ng/mL, p = 0.013). Changes in levels of metabolites mostly involved those related to lipid metabolism. In the early-onset group, acylcarnitine analog and propylparaben levels were downregulated and negatively correlated with the PAI-1 concentration whereas LPC (22:6) and LPC (18:0) levels were upregulated and positively correlated with the PAI-1 concentration. Dietary and clinical features, serum adipokine concentrations, and metabolites differed according to whether the gout is early-onset or late-onset. The mechanisms of gout may differ between these groups and require different treatment approaches.

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A Complete Remission (CR) Is Not a Prerequisite for Prolonged Survival after Autotransplants for Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.926.926 ◽

2004 ◽

Vol 104 (11) ◽

pp. 926-926 ◽

Cited By ~ 2

Author(s):

Guido Tricot ◽

Maureen Reiner ◽

Jeffrey Sawyer ◽

John Crowley ◽

Bart Barlogie

Keyword(s):

Overall Survival ◽

Acute Leukemia ◽

Tumor Burden ◽

Time Dependent ◽

Prolonged Survival ◽

P Value ◽

High Dose ◽

Cytogenetic Abnormalities ◽

Variate Analysis ◽

The Impact

Abstract In acute leukemia prolonged survival is impossible without obtaining a CR. Based on the acute leukemia model, myeloma therapy has gradually been intensified with the aim to increase the CR rate as a first important step to improve overall survival (OS). Although patients with abnormal metaphase cytogenetics have a significantly inferior outcome in terms of event-free and overall survival, the CR rate is similar for patients with and without cytogenetic abnormalities, indicating that CR may not be a good prognostic indicator of ultimate outcome. To address the importance of obtaining a CR for OS, we analyzed our Total Therapy I (VADx3-high dose cyclophosphamide 6g/m2 with stem cell collection-EDAP-melphalan-based tandem transplants-α interferon maintenance) data in those patients who had not received any treatment prior to enrollment (N=155), received at least one transplant (N=135) and were alive one year after the first transplant (N=132). Kaplan-Meier curves were generated using a 1 year landmark to compensate for the guaranteed time of CR patients, but thereby excluding patients who died within the first year after the first autotransplant (N=3). The 1-year landmark was chosen because the large majority of CR patients (75%) had achieved their CR at 1 year after the first transplant. In addition, a time-dependent co-variate analysis for CR was performed, including the 135 patients. The median follow-up of these patients was 10.5 years. The 9 year OS after the landmark, i.e., 10 years after the first transplant, was 41% (95% confidence interval: 26, 55) for CR patients versus 37% (26, 47) for no CR patients (i.e., PR and <PR) with a logrank p value of 0.71 (Figure 1). Using a time-dependent co-variate analysis for CR, achieving a CR was not significantly related to OS (Hazard Ratio: 0.83; p value 0.39). Only the presence of metaphase cytogenetic abnormalities (HR: 2.0; p=0.005), LDH > 190 U/L (upper limit of normal) (HR: 2.0; p=0.01) and CRP >4.0mg/L (HR: 1.6; p=0.03) were significant for OS. When the importance of CR was assessed separately for patients with (N=43) and without (N=84) abnormal cytogenetic (cytogenetic information was missing on 5 patients), no survival benefit for CR patients was seen in either subgroup (p values 0.52 and 0.32, respectively) and similarly, using the time-dependent co-variate analysis for CR, there was no significant benefit for OS of attaining a CR in either group (p value: 0.7 and 0.5, respectively). We conclude that prolonged survival (>10 years) is observed in a substantial proportion of myeloma patients receiving a tandem autotransplant-based regimen, irrespective of the completeness of response to tandem transplants. The inherent genetic features of the myeloma and the impact on the micro-environment of the myeloma cells appear to be more important than the absolute tumor burden reduction accomplished by tandem transplants. Our findings may also be a reflection of the insensitivity of CR as an assessment of remaining tumor burden in myeloma and a new definition of CR may be required. Figure Figure

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Post-Transplant Platelet Recovery Kinetics and Its Association with Overall Survival in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Blood ◽

10.1182/blood.v118.21.2049.2049 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2049-2049

Author(s):

Jie Li ◽

Jillian Alyse Deppa ◽

Zahir Ali ◽

Michael Graiser ◽

Amelia Langston ◽

...

Keyword(s):

Overall Survival ◽

Platelet Count ◽

Early Death ◽

Disease Status ◽

P Value ◽

Term Survival ◽

Allogeneic Hsct ◽

Post Transplant ◽

Platelet Counts

Abstract Abstract 2049 Background: Post-transplant thrombocytopenia is universal among recipients of hematopoietic stem cell transplantation (HSCT). We have previously reported a secondary post-transplant thrombocytopenia following autologous HSCT which is associated with poor survival (Ninan MJ, et al., BBMT 2007), however the clinical significance of a fall post-engraftment in platelet counts among recipients of allogeneic HSCT has not been studied. Methods: A total of 929 consecutive pts who underwent allogeneic HSCT between 1993 and 2009 were studied in an IRB-approved retrospective analysis. 55% of pts were male and 45% were female with a median age of 43 ± 12.6 years. Diagnoses included: acute leukemia (423, 46%), chronic leukemia (197, 21%), non-Hodgkin's lymphoma (110, 12%),myelodysplastic syndrome (93, 10%), multiple myeloma (26, 3%), and other less common malignancies (80, 8%). Disease status was classified into five different categories: complete remission (287, 31%), partial remission (297, 34%), refractory (180, 19%), untreated (28, 3%) and incompletely classified (137, 15%). Grafts were obtained from related donors in 595 pts (64%), and unrelated donors in 334 pts (36%), with 55% peripheral blood stem cell (PBSC), 42% bone marrow (BM), and 3% cord blood units or multiple sources. Blood platelet counts and platelet transfusions were collected from 15 days pre-transplant until 100 days post-transplant. Platelet engraftment was defined as a platelet count ≥ 50 x10E3/mcL without a platelet transfusion in the previous 7 days. Pts (n=816) who achieved platelet engraftment and survived at least 30 days were selected for further analysis. Results: The 816 evaluable pts were divided into cohorts based upon their post-transplant survival: 146(18%) who died within 100 days post-transplant (early death); 267 (33%) that survived 100 days −2 years post-transplant (late death), 319 (39%) who survived > 2 years (long-term survival), and 84 (10%) were lost of follow-up within the first 2 years. Transfusion-independent platelet engraftment was achieved at median of 15 days post-transplant with no significant differences seen in the kinetics of initial engraftment among the different pt cohorts. Median platelet counts at different time points post-transplant were plotted for each pt cohort (Figure 1). Pts in the early-death cohort had a continuous decline in median platelet counts from engraftment values of > 50 x10E3/mcL to a median values of ∼20 x10E3/mcL. Univariate analyses indicated that higher platelet counts at day −15 (prior to conditioning) or at day 100 post-transplant were significantly associated with improved overall survival (HR of 0.63 and 0.39 respectively, P < 0.01). Cox-regression analysis was performed to evaluate significance of pre- and post-transplant platelet counts with clinical covariates that have been previously associated with survival including age, diagnosis, disease status and the source of the grafts. The multivariate model confirmed the significant association of the following factors with overall survival: higher platelet counts on day 15 pre-transplant (HR:0.81; 95%Cl:0.70∼0.93; P-value <0.01), the platelet count on day 100 post-transplant (HR: 0.62; 95%Cl:0.55∼0.70; P-value:<0.01 ), a diagnosis of acute leukemia (HR:1.64; 95%Cl:1.13∼2.39; P-value <0.01), a diagnosis of multiple myeloma (HR: 2.12; 95%Cl:1.05∼4.23; P-value= 0.04), a disease status of complete remission (CR) versus not in CR (HR: 0.66; 95%Cl:0.44∼0.97; P-value = 0.04), and age (HR: 1.01; 95%Cl:1.00∼1.02; P-value= 0.08). Kaplan-Meier estimates for survival were performed based upon stratification of pt groups on the platelet count at day-15 pre-transplant or the day +100 post-transplant platelet count (Figure 2). Pts with a platelet count > 80 × 10E3/mcL on day +100 had 5 year survival of more than 50% compared with 30% survival in the pt cohort with platelet counts < 50 x10E3/mcL on day +100. Conclusion: Pts with continuously low platelet count after initial platelet engraftment are at high risk for early death. Higher pre-transplant platelet may be a surrogate for disease status and extent of prior therapy and are associated with long-term survival among pts undergoing allogeneic HSCT. Post-transplant thrombopoiesis at day 100 is highly correlated with long-term survival after allogeneic HSCT, identifying a high-risk group of transplant pts for whom additional treatment strategies are needed. Disclosures: Gleason: Celgene, Merck, Millenium: Consultancy.

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Local and Systemic Inflammatory Markers as Prognostic and Predictive Markers In Locally Advanced Triple Negative Breast Cancer

Tumori Journal ◽

10.1177/0300891620914162 ◽

2020 ◽

Vol 106 (1_suppl) ◽

pp. 30-30

Author(s):

Lamiss Mohamed ◽

Aymn Elsaka ◽

Yomna Zamzam

Keyword(s):

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Inflammatory Markers ◽

Triple Negative ◽

Statistical Significance ◽

Locally Advanced ◽

Disease Free Survival ◽

Complete Response ◽

P Value ◽

Neutrophil Lymphocyte Ratio

Local inflammatory markers have been defined as prognostic and predictive markers in triple negative markers as proved by many studies. The prognostic and predictive value of systemic inflammatory markers such as neutrophil lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) remain to be elucidated. Aim of study: To evaluate pathological complete response (PCR) to neoadjuvant chemotherapy in locally advanced cancer breast in relation to tumor infiltrating lymphocytes(TILs), neutrophil lymphocyte ratio and lymphocyte monocyte ratio as well as overall survival and disease free survival. Patients and methods: In Tanta university Hospital, oncology department form January 2012 to December 2013, 67 patients with locally advanced TNBC stage IIB, IIIB 0r IIIC using TNM 8t h edition . All patients received neoadjuvant chemotherapy in the form of dose dense AC followed by paclitaxel (adriamycin & cyclophosphamide 60 mgm/m2 & 600 mgm/m2 respectively the cycle is repeated every 2 weeks for 4 cycles followed by paclitaxel 175mgm/m2 every 2 weeks for 4 cycles). All cycles with G-CSF support. Pre treatment TILs, NLR and LMR were evaluated with PCR and as prognostic factor of survival. Results: Low NLR has been detected in 74.6% of cases and has been associated with high TILs and this was statistically significant (p value=0.03). High LMR was observed in 80.6% of cases and correlated significantly with TILs (p value =0.003). Pathological CR was found to be associated with high TILs, low NLR and high LMR. In our study we evaluated the pre neoadjuvant systemic and local inflammatory markers as prognostic marker we found that in multivariate analysis, the lymphocyte monocyte ratio maintained their statistical significance with overall survival. While tumor infiltrating lymphocyte maintained their statistical significance as prognostic factors with overall survival and disease free survival. Conclusion: Systemic inflammatory markers can be used as marker of pathological complete response in locally advanced triple negative breast6 cancer with neoadjuvant chemotherapy.

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Immunological and biological changes during ipilimumab (Ipi) treatment and their correlation with clinical response and survival.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8573 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8573-8573 ◽

Cited By ~ 10

Author(s):

Ester Simeone ◽

Giusy Gentilcore ◽

Anna Romano ◽

Antonio Daponte ◽

Corrado Caraco ◽

...

Keyword(s):

Overall Survival ◽

Metastatic Melanoma ◽

Clinical Parameter ◽

Phase Iii ◽

Response To Treatment ◽

Rank Test ◽

P Value ◽

Term Survival ◽

Overall Survival Benefit ◽

The Moment

8573 Background: Ipilimumab (Ipi) is approved in the US as first and second line therapy in patients with metastatic melanoma (MM) and in MM patients with previous therapy in the EU, based on an overall survival benefit shown in a phase III study (Hodi, NEJM 2010). To date, no clinical parameter has been found to be predictive for response to treatment and only few immunologic changes have been identified as potential candidates. Methods: From June 2010 to November 2011 we treated in the Expanded Access Program with Ipi at 3 mg/kg, 95 pre-treated metastatic melanoma patients. The median age was 58 yrs (range 17-84); 10 pts (10,5%) were stage IIIc inoperable, 2 pts (2,1%) stage M1a, 4 pts (4,2%) stage M1b, and 79 pts (83,2%) stage M1c. 30/95 pts had brain metastases and 1/95 spinal cord metastases. All 95 patients were evaluable for response (DCR = CR+PR+SD according the irRC), overall survival, safety, including changes in LDH, CRP (C-reactive protein) and lymphocyte populations (CD4+,CD4CD25+,FOXP3/T-Reg cells). PBMC and sera were collected at week 0, 4, 7, 10 and 12. Results: We found a statistical significant decrease of LDH, CRP and FOXP3/T-Reg cells (p<0.0001; χ2 and Mann-Whitney), and an increase of lymphocyte count (p<.0001) in the responders group. These differences were also correlated to survival (log-rank test). No differences were observed for CD4+ and CD4+CD25+ between responders and non-responders (p=0.39;p=0.83; Mann-Whitney). An ORR of 22.1% (1CR+20PR; 95% CI 13.8-30.4) and a DCR at week 24 of 37.9% (36/95; 28.1-47.6, 95% CI) were observed. Median overall survival was estimated of 7.8 months (95%CI:5.0-10.6), with a p value not evaluable at the moment of the analysis due to insufficient follow-up because of long-term survival. Adverse events were registered in 40% (38/95) of patients and the most frequent were of grade 1 and 2 (pruritus 57.9%; rash 5.3%; thyroditis 5.3%). Conclusions: The decrease of LDH, CRP and T-Reg cells during Ipi treatment suggest these parameters should be further explored as potential predictive markers for response and survival. Given the potential clinical utility of these findings, these data warrants further prospective validation in a randomized trial.

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A propensity-matched analysis of laparoscopic versus open distal pancreatectomy for pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.376 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 376-376

Author(s):

Mustafa Raoof ◽

Sinziana Dumitra ◽

Philip HG Ituarte ◽

Yanghee Woo ◽

Susanne Warner ◽

...

Keyword(s):

Overall Survival ◽

Length Of Stay ◽

Distal Pancreatectomy ◽

Pancreatic Adenocarcinoma ◽

Perioperative Outcomes ◽

P Value ◽

Term Survival ◽

Open Distal Pancreatectomy ◽

Positive Rate ◽

Margin Positive

376 Background: Laparoscopic-assisted distal pancreatectomy (LDP) has improved perioperative outcomes over open distal pancreatectomy (ODP). Concerns regarding failure to achieve proper oncologic resection and compromised survival remain. Methods: Using the National Cancer Database (NCDB), we analyzed patients undergoing distal pancreatectomy for resectable pancreatic adenocarcinoma over a four-year period (2010-2014). Propensity score nearest-neighbor 1:1 matching (PSM) was performed between LDP and ODP patients based on age, sex, race, insurance, hospital volume, comorbidities, T-stage, N-stage, grade, neoadjuvant therapy, adjuvant therapy. Primary outcome was overall survival. Results: Of the 1,947 eligible patients, 605 (31%) underwent LDP. After PSM two well-balanced groups of 544 patients each were analyzed. There was a trend towards improved overall survival (OS) in patients undergoing LDP as compared to ODP (HR: 0.83, 95% CI 0.68-1.0; Median OS 29 vs. 23 months, p = 0.06). Patients undergoing ODP had a higher margin positive rate compared to those undergoing LDP (21.1% vs. 14.9%, p-value = 0.007). Overall conversion rate was 27%. Patients undergoing ODP had comparable outcomes to LDP in regards to median time to chemotherapy (50 vs. 48 days, p-value = 0.96); median nodes examined (12 vs. 12, p-value = 0.61); 30-day mortality (1.6% vs. 1.1%, p-value = 0.43); 90-day mortality (3.5% vs. 2.4%, p-value = 0.28); 30-day readmission rate (8.6% vs. 9.4%, p-value = 0.67). However, the median length of stay was shorter in the LDP group (6 vs. 7 days, p = 0.0001). Conclusions: In the absence of randomized trials, this is the largest comparative study demonstrating LDP as an acceptable alternative ODP, associated with a lower margin positive rate and shorter length of stay, and with no detriment in long term survival.

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Allogenic Stem Cell Transplantation for Secondary CNS Lymphoma: A Retrospective Review of 21 Patients

Blood ◽

10.1182/blood-2019-126253 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3342-3342 ◽

Cited By ~ 1

Author(s):

Cole Sterling ◽

Nina D. Wagner-Johnston ◽

Douglas E Gladstone ◽

Richard F. Ambinder ◽

Lode J. Swinnen ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Residual Disease ◽

Cns Lymphoma ◽

P Value ◽

Myeloablative Conditioning ◽

Advisory Committees ◽

Term Survival ◽

Cns Disease ◽

Post Transplant

INTRODUCTION: Allogeneic blood or marrow transplant (alloBMT) is widely used in relapsed/refractory systemic non-Hodgkin lymphoma. The graft-versus-tumor effect has been thought to be blunted by the immune privilege of the central nervous system (CNS). Communication between the CNS and the systemic immune system suggests that CNS disease could benefit from the graft versus lymphoma (GVL) effect provided by alloBMT. METHODS: The charts of all patients who received post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis between January 2004 and October 2018 were reviewed. Survival statistics were calculated using the Kaplan-Meier method. Differences in time to death between groups were estimated using Cox proportional hazards models. RESULTS: Twenty-one patients with systemic lymphoma involving the CNS were identified. The median age was 59 years (range 24-73); 7 were over the age of 60 and 13 were male. Histology types included diffuse large B cell (71%), Burkitt (10%), T cell (10%), follicular (5%), and anaplastic large cell (5%). Prior to transplant, 12 patients were in complete remission, 9 had residual disease, and 5 had residual CNS disease by imaging. Induction therapy included CNS radiation therapy in 11 of 21 patients (52%) and high-dose methotrexate (HD-MTX) in 10 (48%). Only 1 patient was in first remission, with the remaining 20 in second or later remission. All but 1 patient received non-myeloablative conditioning using fludarabine, cyclophosphamide, and total-body irradiation; the other patient received busulfan and cyclophosphamide. Fifteen patients (71%) had haploidentical donors. Graft source was bone marrow in 18 patients and G-CSF-stimulated peripheral blood in 3. Median overall survival (OS) for the entire cohort was 1375 days (95% confidence interval [CI] 184-NR) and median progression free survival (PFS) was 1375 days (95% CI 112-NR). Three-year overall survival was 51% (95% CI 27-71%). The cumulative incidence of relapse was 29% (95% CI 9-49%) at 3 years, and non-relapse mortality was 20% (95% CI 2-38%) at 1 year. Of the 6 patients who relapsed, 2 were CNS only, 2 were systemic only, and 2 were combined CNS / systemic. There were 2 cases of grade III-IV acute GVHD and 1 case of chronic GVHD involving the mouth. Univariable analysis revealed no predictors of survival in our small data set: age > 60 (hazard ratio [HR] 1.48, 95% CI 0.42-5.29, p-value 0.54), haploidentical donor (HR 4.2, 95% CI 0.53-33.66, p-value 0.17), residual disease (HR 1.3, CI 0.37-4.52, p-value 0.68), and prior CNS radiation (HR 1.5, 95% CI 0.42-5.31, p-value 0.53). DISCUSSION: Allogeneic BMT with non-myeloablative conditioning is potentially curative in patients with secondary CNS lymphoma. Post-transplant cyclophosphamide is well tolerated in this older group. Myeloablative conditioning directed at the CNS is not required for long-term survival. Given its biologic plausibility and potential as a viable treatment option in certain patient populations, the role of alloBMT in CNS lymphoma deserves further investigation. Figure Disclosures Wagner-Johnston: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Jannsen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Swinnen:Pharmacyclics: Consultancy; AbbVie: Consultancy.

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Prognostic Factors in Resected Pancreatic Ductal Adenocarcinoma: Is Neutrophil-Lymphocyte Ratio a Useful Marker?

10.21203/rs.3.rs-1157384/v1 ◽

2021 ◽

Author(s):

Ignacio Guillermo Merlo ◽

Victoria Ardiles ◽

Rodrigo Sanchez-Clariá ◽

Eugenia Fratantoni ◽

Eduardo de Santibañes ◽

...

Keyword(s):

Overall Survival ◽

Pancreatic Ductal Adenocarcinoma ◽

Adjuvant Treatment ◽

Tumor Size ◽

Pancreatic Resection ◽

Perineural Invasion ◽

Undifferentiated Carcinoma ◽

Ductal Adenocarcinoma ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

Abstract Background: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio and its variation pre and post-operatively (delta NLR) in overall survival after pancreatectomy for pancreatic ductal adenocarcinoma at a single centre and to identify factors associated with overall survival.Methods: A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between evaluated factors and overall survival were analyzed using a log-rank test and Cox proportional hazard regression model.Results: Overall, 242 patients underwent complete pancreatic resection for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% CI: 19.5-29) and survival rates at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. NLR and delta NLR were not significantly associated with survival (HR=1.14, 95%CI: 0.77-1.68, p=0.5). Lymph node ratio was significantly associated (HR=1.66, 95%CI: 1.21-2.26, p=0.001) in the bivariate analysis. In multivariable analysis the only factors that were significantly associated with survival were perineural invasion (HR=1.94, 95%CI: 1.21-3.14, p=0.006), surgical margin (HR=1.83, 95%CI: 1.10-3.02, p=0.019), tumor size (HR=1.01, 95%CI: 1.003-1.027, p=0.16), postoperative CA 19-9 level (HR=1.001, p<0.001), and completion of adjuvant treatment (HR=0.53, 95%CI: 0.35-0.8, p=0.002).Conclusion: Neutrophil-lymphocyte ratio and delta NLR were not associated with overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.

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The Importance of Thrombotic Risk Factors in the Development of Idiopathic Sudden Hearing Loss

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029607306399 ◽

2008 ◽

Vol 14 (3) ◽

pp. 356-359 ◽

Cited By ~ 15

Author(s):

Zuleyha Yildiz ◽

Arzu Ulu ◽

Armagan Incesulu ◽

Yalcin Ozkaptan ◽

Nejat Akar

Keyword(s):

Hearing Loss ◽

Patient Group ◽

Sudden Hearing Loss ◽

Cell Protein ◽

Control Group ◽

P Value ◽

Factor V ◽

Plasminogen Activator Inhibitor 1 ◽

Thrombotic Risk ◽

Pai 1

Impaired cochlear blood circulation has been suggested to cause sudden hearing loss. In this study, the role of factor V 1691 G-A (FV 1691 G-A), prothrombin 20210 G-A (PT 20210 G-A), methylene tetrahydrofolate reductase 677 C-T (MTHFR 677 C-T), factor V 4070 A-G (FV 4070 A-G), endothelial cell protein C receptor (EPCR) gene 23-bp insertion, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G mutation was assessed. Fifty-three patients with idiopathic sudden sensorineural hearing loss and 80 individuals comprising the control group were included in this study. The frequency for FV 1691 A was 6.2% in the patient group and 3.7% in the control group, PT 20210 G-A was 1.2% in the patient group and 1.9% in the control group, and FV 4070 A-G was 7.5% in the patient group and 11.3% in the control group. The frequency of MTHFR 677 C-T was significantly higher in the patient group than in the control group, with a P value of .03. PAI-1-675 4G/5G polymorphism was found to be 71.2% and 69.8%, in the control group and the patient group, respectively. The EPCR 23-bp insertion was 0% in the control group and was found in 3 patients (3.7%), which needs further study.

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Surgical Outcomes and Risk Analysis of Primary Pulmonary Sarcoma

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0039-1695784 ◽

2019 ◽

Author(s):

Yoshito Yamada ◽

Tevfik Kaplan ◽

Alex Soltermann ◽

Isabelle Schmitt-Opitz ◽

Didier Schneiter ◽

...

Keyword(s):

Overall Survival ◽

Surgical Resection ◽

Tumor Size ◽

Lung Neoplasm ◽

Incomplete Resection ◽

Pathological Grade ◽

Pathological Stage ◽

Term Survival ◽

Advanced Pathological Stage ◽

Pulmonary Sarcoma

Background Primary pulmonary sarcoma (PPS) is a rare malignant lung neoplasm, and there is very little medical evidence about treatment of PPS. The aim of this study is to clarify the clinical characteristics and therapeutic outcome of patients who underwent surgical resection for PPS. Methods We retrospectively reviewed the records of patients who underwent surgical resection for PPS in our institution between 1995 and 2014. Cases who only underwent biopsy were excluded. Results A total of 24 patients (18 males, 6 females), with a median age of 60 (interquartile range: 44–67) years, were analyzed. The surgical procedures performed in these patients were pneumonectomy (n = 10), lobectomy (n = 11), and wedge resection (n = 3). Complete resection was achieved in 16 patients. The pathological stages (tumor, node, metastases lung cancer classification, 8th edition) of the patients were I (n = 4), II (n = 12), III (n = 2), and IV (n = 5), and there were four cases of lymph node metastasis. The 5-year overall survival rate of the patients was 50% (95% confidence interval [CI]: 29–72). Adverse prognostic factors for overall survival were incomplete resection (hazard ratio [HR]: 4.4, 95% CI: 2.1–42), advanced pathological stage (HR 14, 95% CI: 2.8–66), higher pathological grade (HR 4.5, 95% CI: 1.2–17), and tumor size ≥ 7 cm (HR 4.7, 95% CI: 1.1–21). Conclusions Our series of PPS revealed that incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long-term survival.

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