scholarly journals P09.06 Investigating various patient parameters as prognostic markers for patients with advance stage nasopharyngeal carcinoma undergoing induction chemotherapy followed by Epstein-Barr virus cytotoxic T-lymphocyte immunotherapy

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A30.2-A31
Author(s):  
A Chu ◽  
S Han ◽  
H Toh
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Median Survival ◽  
Cytotoxic T Lymphocyte ◽  
Survival Outcome ◽  
First Line ◽  
Patient Factors ◽  
Initial Stage ◽  
Ebv Dna

BackgroundPrevious prospective phase II study conducted by our research group at the National Cancer Centre Singapore had shown the efficacy of combined induction chemotherapy followed by cytotoxic T-lymphocyte (CTL) immunotherapy as a first-line treatment for advance nasopharyngeal carcinoma (NPC) – i.e. median survival for patients treated with combined therapy was 29.9 months, compared to 17.7 months for patients who received only standard chemotherapy.1 Using the same data set, we further investigate the correlation between various patient factors (Eastern Cooperative Oncology Group (ECOG) score, gender, age, initial stage of cancer, neutrophil-to-lymphocyte ratio (NLR), initial EBV-DNA titre) on overall survival (OS). This is to further validate our hypothesis that the improved OS is due to an effect of treatment and not due to intrinsic patient factors.Materials and MethodsSurvival distribution curves were estimated using the Kaplan-Meier method and differences were compared statistically using log-rank test. IBM SPSS statistics software package (v. 22) was used for the purpose of statistical analysis. Overall survival was defined as time from diagnosis to date of event (date of death/date of last follow-up). For analysis of overall survival, data for patients who were alive or who were lost to follow-up were censored at the end of study period.ResultsIt was revealed that lower ECOG score, a scale used to assess the physical condition of patients, correlated with longer OS while other characteristics such as gender, age, initial stage of cancer, NLR, and initial EBV-DNA titre did not correlate with survival outcomes. ECOG0 patients had a median survival of 146.7 weeks, compared to ECOG1 patients, which had a median survival of 86.6 weeks (hazard ratio: 0.35; 95% CI: 0.14-0.84; P = 0.033).ConclusionsEven though ECOG performance status is found to be statistically associated with survival outcome of patients with advance stage NPC. This result is unsurprising as the prognostic value of ECOG has been well documented in literature, albeit in other cancer types. Other patient parameters such as gender, age, initial stage of cancer, NLR, and initial EBV titre, did not yield significance and did not prognosticate for survival outcome. This finding supports our hypothesis that the improved survival outcomes observed in advance NPC patients treated with chemotherapy followed by EBV CTL-immunotherapy is due to effects of treatment and not because of intrinsic patient factors.ReferenceChia WK, Teo M, Wang WW, Lee B, Ang SF, Tai WM, Chee CL, Ng J, Kan R, Lim WT, Tan SH, Ong WS, Cheung YB, Tan EH, Connolly JE, Gottschalk S, Toh HC. Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma. Mol Ther 2014 Jan;22(1):132–9.Disclosure InformationA. Chu: None. S. Han: None. H. Toh: None.

Maintenance intervention to improve survival in patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment: A prospective multicenter randomized controlled clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6035-6035
Author(s):  
Ying Lu ◽  
Haixin Huang ◽  
Hui Yang ◽  
Xiaohua Hu ◽  
Xianbing Feng ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Maintenance Therapy ◽  
Poor Prognosis ◽  
Observation Group ◽  
First Line ◽  
Metastatic Nasopharyngeal Carcinoma ◽  
Ebv Dna ◽  
Maintenance Intervention ◽  
First Line Treatment

6035 Background: The role of drug maintenance intervention in improving survival outcomes remains controversial.To investigate the safety and effect of Tegafur(S1) maintenance intervention in patients with metastatic nasopharyngeal carcinoma who benefit from the first-line treatment in a multicenter randomized controlled study, and to identify the related biological prognostic factors and guide the individualized treatment choice. Methods: Patients with metastatic nasopharyngeal carcinoma in the Fourth Affiliated Hospital of Guangxi Medical University and other cancer centers who met the inclusion criteria were randomly divided into maintenance therapy group: S1 maintenance therapy until disease progression or intolerance; Observation group: follow-up to disease progression. PFS, overall survival (OS) and adverse reactions of S1 maintenance therapy were compared between the two groups. The correlation between EBV-DNA, human serum amyloid A (SAA) and prognosis was evaluated. Results: Follow-up was conducted to May 2020, with a median follow-up of 19.8 months (6.1-51.3 months), 183 cases were evaluable (88 cases in S1 maintenance treatment group, 95 cases in observation group). Compared with the observation group, the S1 maintenance treatment group significantly increased patients' median PFS (16.2 months vs. 8.7 months, P < 0.001) and median OS (32.1 months vs. 18.2 months, P < 0.001). Reduced the risk of poor prognosis for PFS and OS (PFS: HR 0.305, 95%CI 0.211-0.441, < 0.001; OS: HR 0.363, 95%CI 0.238-0.553, P < 0.001). In the maintenance treatment group, the median S1 treatment lasted for 14 courses (4-58 courses), and the main adverse reactions were grade 1 skin pigmentation, oral mucositis, hand-foot syndrome, nausea, etc. No grade 4 toxic reaction occurred, and it was well tolerated. Compared with observation patients with negative EBV-DNA, observation patients with positive EBV-DNA had a higher risk of poor prognosis for PFS (HR 1.764, 95%CI 1.078-2.887, P = 0.024). The risk of poor prognosis in patients with positive EBV-NDA was significantly reduced by 61.1% ( < 0.001) for PFS and 65.5% (P = 0.001) for OS (P = 0.001). Compared with the observation group with stable SAA expression, S1 maintenance therapy significantly improved the prognosis of patients. Patients with continuous decline in SAA had a 61.9% lower risk of poor prognosis in PFS (P < 0.001) and a 60.2% lower risk of poor prognosis in OS (P = 0.007). Conclusions: For patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment, maintenance therapy of S1 can significantly improve the survival prognosis and is well tolerated. Patients with positive EBV-DNA and continuous decline in SAA may benefit more from maintenance intervention. Clinical trial information: ChiCTR-IOR-16007939.

scholarly journals Plasma Epstein-Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-Jie Chen ◽  
Wen-Na Xu ◽  
Hai-Yun Wang ◽  
Xiao-Xia Chen ◽  
Xue-Qi Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Screening Program ◽  
Southern China ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Objective Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. Materials and methods A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. Results Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. Conclusion Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.

scholarly journals Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma

2020 ◽  
Vol 28 (11) ◽  
pp. 5271-5279 ◽  
Author(s):  
Shuichi Mitsunaga ◽  
Eiji Kasamatsu ◽  
Koji Machii
Keyword(s):  
Overall Survival ◽  
Weight Loss ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cachexia ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
First Line ◽  
Timing Of Onset ◽  
Line Chemotherapy

Abstract Purpose Cachexia influences the patient’s physical wellbeing and quality of life, and the patient’s ability to tolerate their cancer therapies, especially cytotoxic chemotherapy. The purpose of this study was to investigate the frequency and timing of onset of cancer cachexia during chemotherapy and its association with prognosis and toxicity in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We performed a retrospective study in patients who underwent first-line chemotherapy after diagnosis of advanced PDAC between 6 June 2008 and 31 March 2017. Base cachexia (weight loss up to 6 months before starting first-line chemotherapy) and follow-up cachexia (after starting first-line chemotherapy) were defined as weight loss > 2% with a body mass index (BMI) < 20 kg/m2 or weight loss > 5%. Results A total of 150 patients were registered. The median age and BMI were 65 years and 21.7 kg/m2, respectively. Base cachexia occurred in 50% of patients. Follow-up cachexia occurred in 32% within 12 weeks of starting first-line chemotherapy, reaching 64% at 1 year. Overall survival was not significantly different between patients with and without follow-up cachexia, regardless of whether cancer cachexia occurred within 12, 24, or 48 weeks of starting first-line treatment. Appetite loss, fatigue, nausea, and diarrhea were more frequent in patients with follow-up cachexia than in those without follow-up cachexia. Conclusion Follow-up cachexia had an early onset, but was not a prognostic factor for overall survival in patients with PDAC. Some adverse events tended to be more frequent in patients with follow-up cachexia than in those without follow-up cachexia.

A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Wang Fang FangZheng
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Long Term Outcomes ◽  
First Line ◽  
Grade 3

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

Prognostic Impact of Clinical and Tumor Associated Variables in a Population-Based Cohort of Mantle Cell Lymphomas in the Stockholm Region Between 1998–2010

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1592-1592 ◽  
Author(s):  
Stefanie Baumgartner Wennerholm ◽  
Monika Klimkowska ◽  
Lina Nygren ◽  
Eva Kimby ◽  
Birgitta Sander
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Median Survival ◽  
Biological Markers ◽  
Population Based ◽  
Prognostic Impact ◽  
Female Ratio ◽  
Significant Difference ◽  
Mantle Cell

Abstract Abstract 1592 Introduction: Mantle cell lymphoma (MCL) constitutes 3–10% of non-Hodgkin lymphomas and affects predominantly middle-aged to elderly men. The median survival is 3–5 years and seems to improve with new therapeutic regimens. The MCL International Prognostic Index (MIPI) has been proven useful for predicting survival in MCL patients included in clinical trials, but its value in unselected population based MCL cohorts is less well known. Biological markers are increasingly used for prognostication of MCL patients, especially for defining indolent cases. Material and Methods: All 186 patients diagnosed with MCL, confirmed by IHC for cyclinD1 and/or by FISH for t(11;14), between January 1998 and June 2010 in the Stockholm region, were included in a retrospective analysis. Clinical data from patient files, diagnostic biopsies and flow cytometry data were reviewed. Last follow-up was in May 2011. The prognostic value of the following variables, evaluated at the time of diagnosis, were analyzed: age, sex, Ann Arbor stage, ECOG, B-symptoms, Hb, LDH, albumin, lymphocytosis, leukocytosis, splenomegaly, nodal, extranodal and bone marrow involvement, blastoid morphology, expression of CD23, light chain, Ki 67, p53 and nuclear SOX11. Results: The median age at diagnosis was 68.8 years (range 36.2 – 89.9); 67.4 in males and 72.1 in females, respectively. The male: female ratio was 2. Thirty patients had a known malignancy of other type before the MCL diagnosis and 12 acquired a cancer later. In 13 patients the other malignancy was the cause of death. Median overall survival (OS) time was 43 months in the whole cohort and 38 months, when excluding 39 patients receiving ASCT as part of first-line therapy. No statistically significant difference in OS was seen with respect to whether the lymphoma was diagnosed before or after 2005. In the non-transplanted patients (n=149), univariate analysis showed the following clinical variables to be negatively correlated to overall survival: age >65 years, B-symptoms, splenomegaly, ECOG >2, low albumin, and high LDH. The median survival was not reached in the low risk MIPI group, and was 79 and 34 months, in the middle and high risk MIPI group, respectively. Blastoid morphology and p53 positivity (>20%), were negatively correlated to overall survival (both with p<0.0001), as was increasing tumor cell proliferation (measured as a continous variable or using the cut-offs >50%, both with with p<0.0001), but not with cut-off >30% (p=0.061), while SOX11 positivity was related to a prolonged survival (p=0.015). Multivariate analyses showed that age >65 (HR 6.1, p<0,002), ECOG >2 (HR 63, p<0.001), high LD (HR 3.7, p< 0.001), and p53 positivity (HR 5.6, p< 0.0001) remained significant. Clinically indolent MCL, defined as in retrospect not requiring treatment within two years from diagnosis, was seen in 17 patients. In two of these patients the proliferation was >30%, in one >50%, two had a p53 expression >20% and two were SOX11 negative. Therapy was never required in 9 of these initially indolent patients and only one had an autologous transplantion later in the disease course. The median OS was 72 months for the 17 indolent MCL compared with 34 months in patients requiring treatment earlier in their disease (p=0.003). The follow-up time did not differ significantly between the two groups. Conclusions: Compared to data from published clinical trials of advanced MCL, our population-based cohort of 186 cyclin D1 positive MCL patients were diagnosed at an older age, which may contribute to a shorter overall survival. Certain well-established prognostic variables seem to loose significance outside study populations. In the group of 147 non-transplanted patients multivariate analysis showed that only age, ECOG, LDH and p53 positivity were independently associated with overall survival. Leukocytosis as a variable of MIPI had no impact. Neither SOX11, CD23 or other biological markers applied at the time of diagnosis could predict for clinically indolent disease. Disclosures: No relevant conflicts of interest to declare.

Comprehensive Cytokine Profiling in Systemic Mastocytosis: Prognostic Relevance of Increased Plasma IL-2R Levels.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2836-2836 ◽  
Author(s):  
Animesh Pardanani ◽  
Christy Finke ◽  
Terra L Lasho ◽  
Ayalew Tefferi
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Mast Cell ◽  
Median Survival ◽  
Systemic Mastocytosis ◽  
B Cell Lymphoma ◽  
World Health ◽  
Serum Tryptase ◽  
Who Criteria

Abstract Abstract 2836 Background: The clinical phenotype of systemic mastocytosis (SM) is highly variable; establishing prognosis in terms of overall survival or risk of transformation to aggressive disease for those with non-indolent and indolent disease variants, respectively, is not trivial. Similar to other clonal hemopathies, mast cell (MC) activation and/or stromal response to clonal MC expansion likely results in a dysregulated immuno cellular/cytokine profile; analysis of this aspect of SM may provide additional prognostic information within the context of well established parameters such as the World Health Organization (WHO) SM classification system. Here, we conducted a comprehensive analysis of circulating cytokines/chemokines with clinicopathologic and clinical outcome correlations in a cohort of SM patients seen at our institution. Methods: The diagnosis of SM and its subclassification were established according to WHO criteria. Inclusion in this study required availability of archived plasma, bone marrow biopsy, and cytogenetic information at the time of first referral. Follow up information including data on survival and disease progression were updated in July 2012. Concentrations of plasma cytokines were analyzed in duplicate by using Multiplex Bead-Based Luminex technology (Invitrogen, Carlsbad, CA). Results: Forty six SM patients met the above stipulated criteria; 25 (54%) were male and the median age at referral was 61 years (range 21–85). Subclassification of patients per WHO criteria was: indolent SM (ISM) 23 (50%), aggressive SM (ASM) 8 (17%) and SM with associated clonal hematological non-MC lineage disease (SM-AHNMD) 15 (33%). When the distribution of 30 cytokines was considered across the 3 SM sub groups, only interleukin (IL)-8 was significantly different (SM-AHNMD > ISM/ASM; p=0.0002). For ISM patients, increased levels of sIL-2R were associated with presence of B-findings (p=0.0046) including splenomegaly (p=0.001) and serum tryptase levels >200 ng/mL (p=0.0046), and decreased levels of IL-8 and hepatocyte growth factor (HGF) with MC mediator-release symptoms (p <0.05). Increased levels of sIL-2R (r2=0.6; p<0.0001) and RANTES (r2=0.37; p=0.0013) were correlated with bone marrow MC burden, and sIL-2R (r2=0.34; p=0.004) and MIG (r2=0.42; p=0.0012) with serum tryptase levels in ISM patients; similar findings were noted for the overall cohort. At a median follow up of 28 months (range 0–116), 20 (43%) deaths, and 3 (13%) and 1 (2%) transformations to ASM and mast cell leukemia, respectively, were recorded for the overall cohort. In univariate analysis, increased sIL-2R levels were predictive for inferior overall survival (p=0.005); this prognostic significance was maintained in multivariate analysis after adjusting for other known prognostic variables individually (i.e. WHO SM subtypes, age >65 years, hemoglobin <10 g/dL, thrombocytopenia, weight loss or hypoalbuminemia) (all p <0.05). Increased sIL-2R (>75th percentile) effectively stratified patients in the overall cohort into 2 well-delineated risk groups for overall survival (median survival 109 vs. 26 months; p=0.0004) (Figure). This sIL-2R threshold was also able to risk stratify patients within ISM (median survival not reached vs. 38 months) and non-ISM (median survival 31 vs. 5 months) categories (p <0.0001). Conclusions: The current study demonstrates s-IL2R to be a key inflammatory cytokine in SM; it is significantly correlated with a phenotype of high systemic MC burden and in this regard, is an attractive surrogate for treatment response in clinical practice, if validated. The predictive value of sIL-2R for overall survival is akin to similar observations in primary myelofibrosis and diffuse large B-cell lymphoma; in this study, it was noted to be independent of conventional measures of organopathy from MC infiltration, and thus may reflect a novel pathogenetic process in SM, mediated by dysregulated inflammatory and/or immuno cellular pathways. Disclosures: No relevant conflicts of interest to declare.

First Line Treatment of Advanced Stage Hodgkin Lymphoma with Six Cycles of BEACOPPescalated Results in Superior Overall Survival Compared to ABVD: Results of a Network Meta-Analysis Including 10,011 Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 551-551
Author(s):  
Peter Borchmann ◽  
Sven Trelle ◽  
Michaela Rancea ◽  
Heinz Haverkamp ◽  
Volker Diehl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Initial Treatment ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Abstract 551 Background: The best treatment strategy for advanced stage Hodgkin lymphoma (HL) is still a matter of debate. The German Hodgkin Study Group (GHSG) advocates aggressive treatment with BEACOPPescalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) to cure as many patients as possible with first-line therapy. However, BEACOPPescalated may expose patients to excessive toxicity. Treatment with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is supposed to be better tolerable. Proponents of primary ABVD therapy acknowledge a lower progression-free survival (PFS) compared to BEACOPPescalated. However, they argue that relapsing patients can subsequently be cured by high-dose chemotherapy resulting in comparable overall survival (OS). All trials evaluating these two strategies directly were either very small or included patient subgroups only. Although they congruently showed a significant PFS advantage for BEACOPPescalated, they were not powered to detect differences in OS, which obviously is the most important endpoint. Purpose: To assess the benefits and risks of different initial treatment strategies for adult patients with advanced stage HL and to provide patients and physicians with a high-level evidence for treatment decisions. Methods: Data Sources: We developed sensitive search strategies for CENTRAL, MEDLINE, and conference proceedings (searched from 01/1980 to 03/2012). Missing data was obtained from investigators. Study selection: Randomized trials that compared at least two out of twelve pre-defined chemotherapy regimens in adults with advanced stage HL. Two authors independently assessed studies for eligibility. Data extraction: We extracted data and assessed quality of trials in duplicate. The primary outcome was OS. Secondary outcomes included freedom-from-treatment failure (FFTF) and secondary malignancies. Data relates to four or five years of follow-up depending on the status of the trial. Data synthesis: We pooled data using network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian random-effects model. Results are reported relative to ABVD with a hazard ratio (HR) >1 indicating superiority of ABVD. Results: 1,984 references were identified, of which 77 publications, reporting 14 trials, evaluating 11 different regimens were included. A total of 10,011 patients with 59,000 patient-years of follow-up were evaluable for the analyses of survival outcomes. Six cycles of BEACOPPescalated and 8 cycles of BEACOPP-14 were associated with the lowest risk for death of any cause (HR 0.38, 95%-CrI 0.20 to 0.75 and HR 0.43, 95%-CrI 0.22 to 0.86, respectively). Assuming a five-year survival rate of 89% for ABVD this would result in a 5-year survival benefit of 7% and 6% for 6 cycles of BEACOPPescalated and 8 cycles of BEACOPP-14, respectively (95%-CrI 3% to 9% and 2% to 9%, respectively). Eight cycles of BEACOPPescalated were also statistically significantly better as compared to ABVD but the effect was less pronounced. All other treatment strategies showed no statistically significant difference to ABVD. Similar results were obtained for FFTF. Between-trial heterogeneity was negligible in both analyses (tau-square 0.01 and 0.05, respectively). Overall, 327 secondary malignancy and 109 leukemia events accumulated over 57,529 patient-years of follow-up. Given the low number of events we were not able to accurately quantify the risk associated with each regimen; however, Stanford V might be associated with the lowest risk and C(M)OPP/EBV/CAD with the highest risk for secondary leukemias. Limitations: Some of the regimens were only evaluated in one trial. The number of secondary malignancies, especially leukemias, was low. Conclusions: The comparison of different first-line treatment strategies for advanced stage HL in this network meta-analysis shows a significant and relevant OS benefit for both, 6 cycles of BEACOPPescalated and 8 cycles of BEACOPP-14 over standard ABVD treatment. This analysis provides the currently best available evidence on OS of different initial treatment strategies for advanced stage HL patients and therefore adds valid and important information for both, patients and physicians. Disclosures: No relevant conflicts of interest to declare.

Patient Outcomes with Proteosome Inhibitor Bortezomib in Multiple Myeloma at an English District General Hospital

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5745-5745
Author(s):  
Anil Vaikunth Kamat ◽  
Tariq Shafi ◽  
Raphael A. Ezekwesili
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Second Primary ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Second Primary Malignancies

Abstract Bortezomib is a targeted proteosome inhibitor licensed & approved for in multiple myeloma both as first line and in relapsed setting. This is a retrospective non experimental cross sectional quantitative comparative group study using clinical case notes, laboratory & pharmacy records for patients treated with Bortezomib in 2011 & 2012. Outcomes studied included remission status, adverse events, progression free survival and overall survival at follow up. The study also looked at the comparative responses of cohort of patients administered Bortezomib through intravenous & subcutaneous route. The cohort consisted of 33 patients, 21 male, 11 female, median age 71 years, first line 10 patients, second line 23 , median number of cycles in 2011 & 2012 – first line 3 & 8 , second line 5 & 4, respectively. In 2011, 8 received intravenous treatment, 9 were switched from intravenous to subcutaneous route whilst all patients from 2012 received subcutaneous Bortezomib. The most frequently used regimen was Bortezomib Dexamethasone ( VD). The overall response rate ( ORR >/= Minor Response) was: First line 70% (7/10) ; Second line 47.8% ( 11/23); median PFS ( Figure 1) 6 months ( First line: 7 months ; Second line : 6 months) and median overall survival ( Figure 2) at follow up: 9 months ; 39.4 % ( 13/33) First line 8.5 months, Second line 11 months. Subcutaneous Bortezomib was equivalent to intravenous Bortezomib in terms of efficacy & tolerance. Of 33 patients, there were 12 dose reductions. Adverse events reported included: peripheral Neuropathy - grade 3 - 6% ( all grades 27.3%); Diarrhoea - grade 3 - 3% (all grades 6%); Nausea / Vomiting - grade 3 - 3% ( all grades 6%) and Second Primary Malignancies - 12% ( 4 of 33). Mortality at follow up was 20 patients from cohort of 33 ; causes included disease progression in 11, second primary malignancy with disease progression in 4, COPD 2, Systemic Amyloidosis 2, Tuberculosis 1 , Multiple co morbidities 1 and Asthma with mechanical failure in single patient. Second primary malignancies ( 4/33) included Prostate carcinoma ( 1), Renal Cell Carcinoma (1), Neuroendocrine tumour ( 1 ) and Unknown Primary in single patient. Beyond second line treatment, majority (14 of 23 patients; 60.9 %) did not have further active treatment. These data indicate that patient outcomes were modest compared to published data from VISTA and APEX trials. Majority of patients did not have further active treatment beyond second line which suggests the most effective treatment strategy should be used upfront as patients may not be fit to have further lines of therapy despite availability of recently introduced novel targeted agents. A higher percentage of second primary malignancies were noticed in this cohort which should be an area of further clinical research. Figure 1: Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 1:. Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 2: Overall survival with Bortezomib as first line & second line in multiple myeloma Figure 2:. Overall survival with Bortezomib as first line & second line in multiple myeloma Disclosures No relevant conflicts of interest to declare.

Homologous recombination deficiency (HRD): A biomarker for first-line (1L) platinum in advanced pancreatic ductal adenocarcinoma (PDAC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4132-4132 ◽  
Author(s):  
Wungki Park ◽  
Winston Wong ◽  
Kenneth H. Yu ◽  
Anna M. Varghese ◽  
Nadeem Riaz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ductal Adenocarcinoma ◽  
Clinical Implications ◽  
Genomic Profiling ◽  
First Line ◽  
Biomarker Validation ◽  
Definition Of ◽  
Platinum Chemotherapy ◽  
Prospective Database

4132 Background: HRD is an emerging biomarker for platinum therapy in PDAC. The clinical implications regarding differences in outcome between germline and somatic HRD in advanced PDAC treated with 1L platinum is unexplored. Methods: We evaluated overall survival (OS) for advanced PDAC (stage III/IV) based on their pathogenic germline (gHRD) and somatic HRD (sHRD) using integrated genomic profiling from MSK-IMPACT and 1L platinum use. HRD defined by pathogenic alterations from the following genes: BRCA1/2, PALB2, ARID1A/B/2, ATR, ATRX, ATM, BAP1, RAD50/51C/D, BRIP1, NBN, CHECK1/2, FANCA/C, CDK12, and MRE11. Results: Advanced PDAC patients (n=461) treated at MSK enrolled in a prospective database, were evaluated. Median follow-up was 27.6 months (95% CI, 24.6-30.6). Both germline and somatic profilings were available for n=350 (76%) but only somatic profiling was available for n=111 (24%). We identified n=52 patients with gHRD (11.3%), n=42 patients with sHRD (9.1%), and 48 patients with somatic VUS for HRD genes. From all 461 patients, the OS was not different between 1L non-platinum vs. 1L platinum groups (19 M vs. 19.3 M), regardleess of their HRD status. (Table) The OS was superior for gHRD vs. non-gHRD (28.7 M vs. 18.2 M), regardless of 1L treatment choice. However, similar significant OS superiority was neither observed in sHRD vs. non-sHRD, nor in VUS sHRD vs. non-VUS sHRD. In a subgroup analysis of 1L platinum treated patients, the OS was superior in gHRD vs. non-gHRD (NR vs. 17.9 M); however, there was no OS difference between sHRD and non-sHRD. Conclusions: In advanced PDAC patients, only gHRD predicted better overall survival for first-line platinum chemotherapy. These findings emphasize the importance of germline mutation testing of HRD in PDAC. Biomarker validation and functional definition of HRD such as loss of heterozygosity analysis is underway. [Table: see text]

Small cell carcinoma of the prostate: National patterns of care and outcomes.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 9-9
Author(s):  
Zachary D. Horne ◽  
Ryan P Smith ◽  
Sushil Beriwal ◽  
Ronny Kalash ◽  
Ashwin Shinde ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Median Survival ◽  
Systemic Therapy ◽  
Cell Cancer ◽  
Small Cell ◽  
Treatment Modalities ◽  
Cancer Data

9 Background: Small cell prostate cancer (SCPC) is a rare entity with treatment patterns extrapolated from small cell cancer of the lung. Outcomes have been evaluated in small series but prognostic factors are relatively poorly defined. Methods: We utilized the National Cancer Data Base to analyze men diagnosed with SCPC from 2004-2015. Only men with known clinical TNM staging, treatment modalities, and follow up were included. Overall survival (OS) was analyzed and compared with Kaplan-Meier, log-rank, and Cox proportional hazards ratios. Associations with baseline and tumor properties were performed with Chi-squared, independent t-test, and bivariate regression analyses. Results: 800 men with SCPC were identified. Median PSA was 79.0 ng/dL. 55.6% of men had cM1 disease at diagnosis, 31.4% had cN0M0 disease, and 13.0% were cN1M0. Median follow up was 12.4 months for all patients and 19.3 months for cM0 patients. Median survival for cM1, cN0M0, and cN1M0 patients was 9.8, 28.5, and 17.1 months, respectively (p<0.001). In cM0 patients, 66 (18.7%) underwent radical prostatectomy (RP), 177 (50.1%) received radiation therapy (XRT), and 195 (45.2%) received chemotherapy (CT). Median survival for men undergoing RP was not reached vs those who did not undergo RP (p<0.001). XRT also showed a trend towards improved median OS (25.2 vs. 19.1 months, p=0.139). On multivariable analysis for cM0 men, only age (HR 1.044 [95% CI 1.025-10.64] p<0.001), cN1 (HR 1.378 [95% CI 1.001-1.898] p=0.050, RP (HR 0.429 [95% CI 0.259-0.709] p=0.001), and XRT (HR 0.520 [95% CI 0.384-0.704] p<0.001) were predictive for overall survival. When examining only men who received systemic therapy, XRT was the only additional treatment modality to exhibit a survival benefit (HR 0.623 [95% CI 0.425-0.912] p=0.015). Of men with cM1 disease, 78 (17.5%) underwent definitive local therapy (RP/XRT), but no difference in OS was observed. Conclusions: Small cell prostate cancer is an aggressive disease with the majority of men presenting with metastases. In those with pelvis-confined disease who are fit for systemic therapy, radiation therapy to the primary should be considered.

Sign in / Sign up

Export Citation Format

Share Document