Venous Thromboembolism Is Associated with Increased Mortality in Patients with Multiple Myeloma

Abstract Introduction: Previous studies have demonstrated conflicting results regarding the effect of venous thromboembolism (VTE) on survival in patients with multiple myeloma (MM). Recently, a population-based study demonstrated inferior overall survival in patients with MM and VTE (Kristinsson 2012). Given the nature of the data, the prior study was unable to verify venous thrombotic event or adjust for known confounding prognostic risk factors. In an attempt to verify the impact of VTE on survival in MM, we studied outcomes in a nationwide population of United States Veterans with MM. Methods: Patients with newly diagnosed MM treated within the Veterans Health Administration (VHA) system between September 1, 1999 and September 30, 2009 were identified within the VHA Central Cancer Registry. To avoid including patients with precursor states (i.e. monoclonal gammopathy of undetermined significance or smoldering myeloma), patients who did not receive treatment within 6 months of diagnosis were excluded. The cohort was followed using administrative data through April 22, 2013. Data on age, sex, race, body mass index (BMI), co-morbidities, treatment including transplant status, hemoglobin (HGB), albumin, and renal function were obtained. VTE was identified using an algorithm consisting of a combination of VTE international classification of diseases (ICD)-9 codes and VTE treatment data. Cox proportional hazards regression modeling was used to assess the association between VTE and overall survival while controlling for known prognostic factors. Results: The final analytic cohort consisted of 2785 patients of which 190 developed VTE after MM diagnosis (6.8%). After controlling for age, race, BMI, medical comorbidities, baseline lab characteristics, year of diagnosis, and upfront treatment with a novel agent (thalidomide, bortezomib, or lenalidomide), patients with MM and VTE had a 46% increased risk of death at 2 years compared to those without (table 1). This risk persisted at 5-year analysis; however, was no longer statistically significant (HR 1.16; 95% CI, 0.95-1.40). Conclusion: After controlling for known MM prognostic factors, VTE was significantly associated with increased mortality in the 2-years following MM diagnosis. Whether the observed increase in mortality is a direct result of VTE could not be determined in this study. Further study of MM patients with a high-risk for VTE, including studies of thromboprophylaxis, could clarify the significance of this association. Table 1:Increased Risk of Death from VTE in 2,785 US Veterans with MMHR for death within 2 years of MM diagnosis (95% CI)HR for death within 5 years of MM diagnosis (95% CI)VTE1.46 (1.13-1.89)1.15 (0.95-1.40)BMI < 18.5 25 <= BMI < 30 BMI >= 301.45 (1.09-1.93) 0.87 (0.76-0.99) 0.76 (0.65-0.89)1.50 (1.18-1.92) 0.87 (0.79-0.97) 0.78 (0.69-0.88)Age (year)1.01 (1.00-1.02)1.02 (1.01-1.02)Race (AA vs. non)0.87 (0.76-0.99)0.88 (0.79-0.97)HGB mg/dL1.30 (1.15-1.47)1.26 (1.14-1.39)HGB Unknown mg/dL (n=152)0.98 (0.73-1.30)0.88 (0.71-1.10)CrCl < 30 ml/min1.47 (1.28-1.68)1.42 (1.27-1.59)CrCl Unknown ml/min (n=184)1.15 (0.89-1.49)1.11 (0.90-1.10)Albumin <=3 g/dL1.42 (1.25-1.61)1.26 (1.14-1.40)Albumin Unknown g/dL (n=366)0.76 (0.62-0.94)0.85 (0.73-1.00)Year of Diagnosis0.99 (0.96-1.01)0.97 (0.95-0.99)Charlson Comorbidity Index1.08 (1.06-1.11)1.07 (1.05-1.10)Transplant0.22 (0.15-0.31)0.46 (0.38-0.55)Upfront Treatment with Novel Therapy0.47 (0.42-0.53)0.63 (0.57-0.70) Disclosures Carson: Spectrum: Consultancy; Celgene: Consultancy, Speakers Bureau.

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TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽

10.1182/blood.v114.22.4866.4866 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4866-4866

Author(s):

Luciana Correa Oliveira de Oliveira ◽

Juliana Alves Uzuelli ◽

Ana Paula Alencar de Lima Lange ◽

Barbara Amelia Aparecida Santana-Lemos ◽

Marcia Sueli Baggio ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Prognostic Factors ◽

Bone Disease ◽

Cox Regression ◽

Conflicts Of Interest ◽

Newly Diagnosed ◽

Significant Difference ◽

The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

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Expression of Phosphorylated Signal Transducer and Activator of Transcription 5 (pSTAT5) Is Associated with An Increased Risk of Death In Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v116.21.1675.1675 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1675-1675

Author(s):

Anna Brady ◽

Sarah Gibson ◽

Lisa Rybicki ◽

Eric Hsi ◽

Edward Copelan ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Prognostic Factors ◽

Myeloid Leukemia ◽

Signal Transducer ◽

Newly Diagnosed ◽

Risk Of Death ◽

Increased Risk ◽

History Of ◽

Acute Myeloid

Abstract Abstract 1675 Background: Acute myeloid leukemia (AML) is characterized by rapid growth, resistance to therapy, and poor overall survival. Clinical and biologic prognostic markers can help define pathogenesis, guide treatment, and identify novel therapies. Phosphorylated signal transducer and activator of transcription 5 (pSTAT5) is one such potential marker. The transcription factor STAT5 regulates many aspects of cell growth, survival, and differentiation. Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including AML. We investigated whether the level of pSTAT5 expression correlates with complete remission (CR) rates, progression-free survival (PFS), and overall survival (OS) in patients (pts) with newly diagnosed AML. Methods: From 1999 to 2005, all adult pts with newly diagnosed AML (WHO criteria) receiving induction chemotherapy and with an available diagnostic bone marrow biopsy performed at our institution were evaluated. B5-fixed bone marrow core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed using 1 mm cores. The cores were arrayed in duplicate in the majority of samples. Immunohistochemistry was performed for pSTAT5 with anti-pSTAT5 a/b Y695/99 mouse monoclonal antibody (AX1; Advantex Bioreagents) using automated stainers and heat-induced epitope retrieval. In each case, five hundred blasts were counted. The percentage of cells staining positive for pSTAT5 expression was determined by a pathologist blinded to clinical results. Standard metaphase karyotypes were classified into cytogenetic (CG) risk groups by CALGB criteria. Cox proportional hazards analysis was used to identify univariate and multivariate prognostic factors for CR, PFS, and OS, including age at diagnosis, history of an antecedent hematologic disorder (AHD), WBC at diagnosis, pSTAT5 expression, and CG risk group. Results: Adequate tissue and clinical data were available in 112 pts. The median age was 57 years, and median WBC at diagnosis 12.0 K/ μL. Twenty six percent of pts had favorable CG, 41% intermediate risk, 27% high risk, and 6% other (unknown or could not be classified). Nineteen percent of pts had an AHD. pSTAT5 expression was absent in 58% of pts. The remainder of the pts had: 1–5% pSTAT5 (25% of pts), 10% pSTAT5 (11% of pts), 20% pSTAT5 (4% of pts), 30% pSTAT5 (1% of pts), and 50% pSTAT5 (2% of pts). Seventy percent of all pts achieved a CR following induction chemotherapy. Sixty-four percent of pts received post-remission chemotherapy, 3.6% an autologous transplant, and 13.6% an allogeneic transplant in first CR. Median PFS and OS were 9.6 months and 16.0 months, respectively. On univariate analysis, age, history of AHD, WBC at diagnosis, CG risk, and any pSTAT5 expression were prognostic factors for PFS and OS. In multivariable analyses controlling for the above prognostic factors, pSTAT5 expression > 0 was also significantly associated with an increased risk of death (HR 1.96, 95% CI 1.19–3.23, p=0.008), progression or death (HR 1.64, 95% CI 1.01–2.66, p=0.046), and relapse after achieving CR (HR 2.31, 95% CI 1.16–4.63, p=0.018). pSTAT5 expression was not a predictor of achievement of CR. Conclusions: pSTAT5 expression in newly diagnosed adults with AML is associated with a decreased PFS, decreased OS, and increased risk of relapse. Validation of its prognostic value requires additional study. Agents targeting this signaling pathway might improve the outcome of pts with AML. Disclosures: No relevant conflicts of interest to declare.

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Comorbidities Impact Survival in Multiple Myeloma: Analysis of the Veterans Health Administration National Database

Blood ◽

10.1182/blood.v120.21.760.760 ◽

2012 ◽

Vol 120 (21) ◽

pp. 760-760

Author(s):

Tanya Wildes ◽

Suhong Luo ◽

Graham A Colditz ◽

Kenneth R. Carson

Keyword(s):

Cardiovascular Disease ◽

Multiple Myeloma ◽

Renal Impairment ◽

Proportional Hazards ◽

First Year ◽

Risk Of Death ◽

Increased Risk ◽

Comorbidity Index ◽

The Impact ◽

Over Time

Abstract Abstract 760 Introduction: The incidence of multiple myeloma (MM) increases with age, and the prognosis worsens. Comorbidities increase in prevalence with age, yet little is known about the impact of comorbid medical conditions on outcomes in MM. Methods: In a retrospectively-assembled cohort study, all patients with MM diagnosed between 1998 and 2009 at a Veterans' Administration (VA) hospital were identified in the VA central cancer registry. Patients who received no treatment within 6 months of diagnosis were excluded, eliminating those with smoldering myeloma or who received supportive care only. Comorbidities were ascertained from ICD-9 codes present prior to the diagnosis of MM, and categorized using the Romano adaptation of the Charlson Comorbidity Index (CCI). The independent effects of age, race and comorbidities were examined using Cox proportional hazards modeling. The impact of individual comorbidities on survival was also examined, controlling for age and race. Results: A total of 2,968 patients were identified. The median age was 69 (range 27–92). The vast majority of patients (98%) were male; 28.6% of the patients were black. The median Charlson Comorbidity Index score was 2 (range 0–13). The frequencies of selected comorbidities were: diabetes (31%), renal impairment (23.8%), cardiovascular comorbidities (38.8%) and pulmonary (26.6%). The median overall survival (OS) for the entire cohort was 28.6 months at a median follow up of 26.8 months (range 0–137 months). On multivariate analysis, age was significantly associated with mortality [Hazard Ratio (HR) 1.03 per year (95% confidence intervals (CI) 1.03–1.04), p<0.0001]. Race was not significantly associated with survival [HR 0.99 (95% CI 0.90–1.09), p=0.81]. The median OS, adjusted for age and race, was 36.5 months for patients with no comorbidities, 33.9 months for patients with a CCI score of 1–2, 25.6 months for patients with a CCI score of 3–4 and 20.2 months for patients with a CCI score ≥5. The impact of comorbidities on survival violated the proportional hazards assumption, with a cut-point at 1 year, indicating that the influence of comorbidities varied over time. Relative to those with no comorbidities, the HR for death among those with a CCI score 1–2 was 1.20 (0.97–1.48) in the first year, and 1.03 (95% CI 0.89–1.18) subsequent to the first year; among those with a CCI score 3–4, the HR for death was 1.67 (95% CI 1.34–2.08) in the first year and 1.23 (95% CI 1.05–1.45) subsequently; among those with a CCI score ≥5, the risk of death in the first year doubled [HR 2.15 (95% CI 1.73–2.67)] and was increased 40% subsequently [HR 1.42 (95% CI 1.19–1.69)]. Individual prevalent comorbidities were then examined. Cardiovascular disease, renal impairment, and pulmonary disease were all significantly associated with mortality. In the first year after diagnosis, cardiovascular disease was associated with a 55% increase in mortality [HR 1.55 (95% CI 1.35–1.78)] while, subsequent to the first year, the risk was only increased about 20% [HR 1.19 (95% CI 1.07–1.39)]. The impact of renal impairment and pulmonary impairment did not vary over time; both were associated with a 25% increased risk of death [renal impairment HR 1.26 (95% CI 1.14–1.38); pulmonary disease HR 1.24 (95% CI 1.13–1.37)]. Diabetes was not associated with survival (HR 1.02, p=0.64) after controlling for age, race and cardiovascular, pulmonary or renal impairment. Conclusion: Age and comorbidities are independently associated with increased risk of mortality in MM. The influence of comorbidities varies over time, with the greatest impact noted in the first year after diagnosis of MM among those with a CCI score ≥3 and with cardiovascular disease. Further study is needed to determine whether this increased early mortality is related to increased risk of toxicity of therapy, inadequate MM therapy or both. Disclosures: No relevant conflicts of interest to declare.

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Persistent Overall Survival Benefit and No Increased Risk of Second Malignancies With Bortezomib-Melphalan-Prednisone Versus Melphalan-Prednisone in Patients With Previously Untreated Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2012.41.6180 ◽

2013 ◽

Vol 31 (4) ◽

pp. 448-455 ◽

Cited By ~ 168

Author(s):

Jesús F. San Miguel ◽

Rudolf Schlag ◽

Nuriet K. Khuageva ◽

Meletios A. Dimopoulos ◽

Ofer Shpilberg ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Final Analysis ◽

Incidence Rates ◽

Phase Iii ◽

Second Primary ◽

Risk Of Death ◽

Increased Risk ◽

Second Primary Malignancies

Purpose This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies. Patients and Methods In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients. Results After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age ≥ 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates. Conclusion VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP.

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Effect of palliative surgery, chemotherapy, and radiation in stage IV pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15707 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15707-e15707 ◽

Cited By ~ 1

Author(s):

Brooke Vuong ◽

Ahmed Dehal ◽

Amanda N Graff-Baker ◽

Shu-Ching Chang ◽

Leland Foshag ◽

...

Keyword(s):

Overall Survival ◽

Palliative Therapy ◽

Stage Iv ◽

Multimodality Treatment ◽

Palliative Surgery ◽

Cancer Data ◽

Risk Of Death ◽

Dismal Prognosis ◽

Increased Risk ◽

The Impact

e15707 Background: Despite significant advances in multi-modality treatment for pancreatic adenocarcinoma (PC), prognosis for stage IV PC remains poor. While reducing suffering and optimizing quality of life are the primary goals of palliative therapies, these interventions may extend overall survival. We examined the impact on survival when aggressive palliative treatments including surgery, chemotherapy, or radiation were employed in end-of-life care. Methods: The 2004-2014 National Cancer Data Base (NCDB) was queried to identify patients with stage IV PC that did not undergo primary surgical resection. Univariate (Kaplan Meier and log-rank) and multivariable (Cox proportional hazard) analyses were used to assess the associations between patient characteristics, use of palliative therapies, and overall survival. Results: Of 72,736 patients identified with metastatic stage IV PC, 2,097 (3%) underwent surgical palliation (ST), 5,615 (8%) received palliative chemotherapy (CT), 940 (1%) received palliative radiation (RT), 1,163 (2%) received multimodality treatment (MMT), and 62,921 (87%) had no aggressive palliative intervention (NT). The choice of palliative therapy, if any, was influenced by all demographic and tumor variables except for gender (all p < 0.001). Median OS was greatest after CT (5.09 months, p < 0.001) compared to any other modality (NT: 3.45months, ST: 3.71months, RT: 3.25months, MMT: 4.47months). This remained true regardless of age, gender, race/ethnicity, insurance, and facility type. After adjusting for all demographic and tumor factors, use of CT decreased the annual risk of death by 20% (HR = 0.8; 95%CI [0.77, 0.82]) and MMT by 10% (HR = 0.9; 95%CI [0.84, 0.96]). Employment of RT increased risk of death by 9% (HR = 1.09; 95%CI [1.01, 1.17]) and ST did not affect OS (HR = 1.01; 95%CI [0.96,1.06]). Conclusions: Despite advances in palliative treatments, Stage IV PC arries a dismal prognosis. Palliative RT may shorten survival. Equivalent survival for ST versus NT suggests that this may be beneficial in the appropriate patient. Palliative CT independently improved survival by approximately 6 weeks and should be considered in patients that want to extend survival and can tolerate the toxicity.

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Stereotactic radiosurgery (SRS) for brain metastasis (BM) in hormone receptor positive (HR+) HER2 negative breast cancer (BC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.1069 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 1069-1069

Author(s):

Akshara Singareeka Raghavendra ◽

Chao Gao ◽

Fuchenchu Wang ◽

Ran An ◽

Yan Wang ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Salvage Therapy ◽

Brain Lesion ◽

Multivariable Analysis ◽

Karnofsky Performance Score ◽

Performance Score ◽

Risk Of Death ◽

The Impact

1069 Background: With the increase of the utilization of SRS for the treatment of oligometastatic BM over surgical reaction or whole brain radiation therapy (WBRT), we sought to evaluate the impact of SRS on overall survival in HR+Her2- BC and prognostic factors associated with SRS. Methods: We reviewed prospectively collected data in the electronic data bases of the breast medical, surgical and radiation oncology departments at MD Anderson cancer center. We aimed at identifying HR+HER2- BC patients who received upfront SRS for BM’s between 08/10/2009 and 02/27/2018.Overall survival was defined as the time from the first SRS to last follow-up/death. Multivariate analysis by the Cox proportional hazards regression analysis was performed to evaluate the prognostic factors (age at BM, stage, Karnofsky performance score (KPS), symptomatic BM, BM at 1stdistant metastatic presentation, extracranial Disease, treatment history, salvage therapy, number of brain lesion treated) of SRS that influenced survival. Results: A total of 125 patients were identified, and we are reporting on 68 with completed analysis. Median age at time of first SRS was 53.86 years. 51 patients of the 68 were deceased at the time of this analysis and 17 patients were alive at the time of last follow-up. 49 patients (72.06 %) presented with radiation necrosis after SRS; 36 patients (52.94 %) presented with BM as 1st distant metastasis including metastasis to other sites. Number of BM’s lesions <4 was 60 (88.2%) and >=4 was 7 (10.3%). The median follow-up from time of first SRS for survivors was 10.84 months. 24 (35.29%) received two or more sessions of SRS and the mean time between first and second SRS sessions for these patients was 14.24 months. Median time from first SRS to second SRS for ER+HER2− patients was 10.84 months (n = 24); on multivariable analysis, higher Karnofsky performance score (KPS) was associated with better survival compared to no salvage therapy. Patients with KPS>90 (p=0.005) had better survival and reduced the hazard by a factor of 0.33 (or 67%). Receiving SRS (p=0.0003) or SRS+WBRT (0.0001) as salvage therapy reduced the hazard (risk of death) by 86% and 85%, respectively. Conclusions: SRS is an effective treatment modality for HR+HER2- BM from BC. Patients who received SRS or SRS and WBRT, KPS >90 had better survival than patients who didn’t receive any salvage therapy. Updated data will be available at the time of the presentation.[Table: see text]

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The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy: a population-based cohort study

Diseases of the Esophagus ◽

10.1093/dote/doz079 ◽

2019 ◽

Vol 33 (6) ◽

Author(s):

Alfred Adiamah ◽

Lu Ban ◽

Joe West ◽

David J Humes

Keyword(s):

Gastric Cancer ◽

Cohort Study ◽

Venous Thromboembolism ◽

Adjuvant Chemotherapy ◽

Cumulative Incidence ◽

Population Based ◽

Risk Of Death ◽

Increased Risk ◽

Esophagogastric Cancer ◽

The Impact

SUMMARY To define the incidence of postoperative venous thromboembolism (VTE) and effects of chemotherapy in a population undergoing surgery for esophagogastric cancer. This population-based cohort study used linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data from England to identify subjects undergoing esophageal or gastric cancer surgery between 1997 and 2014. Exposures included age, comorbidity, smoking, body mass index, and chemotherapy. Crude rates and adjusted hazard ratios (HRs) were calculated for rate of first postoperative VTE using Cox regression models. The cumulative incidence of VTE at 1 and 6 months was estimated accounting for the competing risk of death from any cause. Of the 2,452 patients identified, 1,012 underwent gastrectomy (41.3%) and 1,440 esophagectomy (58.7%). Risk of VTE was highest in the first month, with absolute VTE rates of 114 per 1,000 person-years (95% CI 59.32–219.10) following gastrectomy and 172.73 per 1,000 person-years (95% CI 111.44–267.74) following esophagectomy. Neoadjuvant and adjuvant chemotherapy was associated with a six-fold increased risk of VTE following gastrectomy, HR 6.19 (95% CI 2.49–15.38). Cumulative incidence estimates of VTE at 6 months following gastrectomy in patients receiving no chemotherapy was 1.90% and esophagectomy 2.21%. However, in those receiving both neoadjuvant and adjuvant chemotherapy, cumulative incidence following gastrectomy was 10.47% and esophagectomy, 3.9%. VTE rates are especially high in the first month following surgery for esophageal and gastric cancer. The cumulative incidence of VTE at 6 months is highest in patients treated with chemotherapy. In this category of patients, targeted VTE prophylaxis may prove beneficial during chemotherapy treatment.

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Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities

Blood Advances ◽

10.1182/bloodadvances.2020002218 ◽

2020 ◽

Vol 4 (15) ◽

pp. 3509-3519 ◽

Cited By ~ 1

Author(s):

Nadine Abdallah ◽

Patricia Greipp ◽

Prashant Kapoor ◽

Morie A. Gertz ◽

Angela Dispenzieri ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Characteristics ◽

Tumor Burden ◽

Disease Stage ◽

Cytogenetic Abnormalities ◽

Chromosome 1Q ◽

Risk Of Death ◽

High Tumor Burden ◽

Increased Risk ◽

The Impact

Abstract A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities in multiple myeloma (MM). It is unclear whether +1q is independently associated with decreased overall survival (OS). The objective of this study was to evaluate the impact of +1q on clinical characteristics, treatment response, and survival outcomes. We included 1376 Mayo Clinic patients diagnosed with MM from 2005 to 2018 who underwent fluorescence in situ hybridization testing at diagnosis with a panel including the +1q probe. A gain in 1q was found in 391 patients (28%) and was associated with anemia, hypercalcemia, high tumor burden, International Staging System (ISS) stage 3, high-risk (HR) translocations, and chromosome 13 abnormalities. There was no difference in overall response or deeper responses to proteasome inhibitor (PI)–, immunomodulatory drug (iMiD)–, or PI plus IMiD–based induction. Time to next treatment was shorter in patients with +1q compared with those without +1q (19.9 vs 27.7 months; P < .001). On univariate analysis, +1q was associated with increased risk of death (risk ratio [RR], 1.9; P < .001), and decreased OS was seen in all treatment groups. +1q was independently associated with decreased OS on multivariate analysis when other HR cytogenetic abnormalities, ISS stage 3, and age ≥70 years were included (RR, 1.5; P < .001). Gain of >1 copy of 1q was not associated with worse OS compared with gain of 1 copy (4.9 vs 4.3 years; P = .21). +1q was associated with high tumor burden, advanced disease stage, and HR translocations. It is independently associated with decreased OS, even in the setting of novel therapy and transplant.

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The Impact of the NOD2/CARD15 Variant (3020insC) and PSMA6 Polymorphism (-8C>G) on the Development and Outcome of Multiple Myeloma

BioMed Research International ◽

10.1155/2020/7629456 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

S. Zmorzyński ◽

S. Popek-Marciniec ◽

W. Styk ◽

M. Wojcierowska-Litwin ◽

I. Korszeń-Pilecka ◽

...

Keyword(s):

Multiple Myeloma ◽

Progressive Disease ◽

Bone Marrow Cells ◽

Risk Of Death ◽

Automated Dna Sequencing ◽

Increased Risk ◽

Pcr Rflp ◽

Relationship Of ◽

The Impact

Introduction. Multiple myeloma (MM) is a hematological malignancy characterized by genetic variety. The 3020insC variant of the NOD2/CARD15 gene results in the upregulation of proinflammatory cytokines. Chronic inflammation and abnormal function of the proteasome system may lead to MM development. The polymorphism (-8C>G) in the PSMA6 gene affects proteasome activity. The aim of our study was to analyze the possible relationship of NOD/CARD15 and PSMA6 genes with the risk of development and outcome of MM, as well as the sensitivity to bortezomib (proteasome inhibitor) in cell cultures derived from MM patients. Objects and Methods. Genomic DNA from 100 newly diagnosed MM patients and 100 healthy blood donors was analyzed by methods such as PCR-RFLP (for PSMA6 genotyping) and automated DNA sequencing (for NOD2/CARD15 genotyping). In a subgroup of 50 MM patients, nucleated bone marrow cells were treated with bortezomib in vitro. Results. Patients with PSMA6 CG+GG genotypes had higher chances for progressive disease (OR=5.0, 95% CI 1.07-23.16, p=0.05), shorter overall survival taking into account the type of treatment (p=0.039), and increased risk of death due to MM at the level of tendency (OR=4.74, 95% CI 1.02-21.97, p=0.06). The presence of NOD2/CARD15 3020insC decreased the risk of renal dysfunction in MM (OR=0.23, 95% CI 0.07-0.74, p=0.009). The analyzed changes in NOD2/CARD15 and PSMA6 genes did not impact the MM risk. In an in vitro study, bortezomib increased the number of apoptotic cells at 8 nM and 12 nM between wild-type and 3030insC variants of NOD2/CARD15 (p=0.018 and p=0.03, respectively). Conclusion. The presented results suggest a possible impact of PSMA6 CG+GG genotypes on the MM outcome and the association of the NOD2/CARD15 variant with bortezomib in vitro sensitivity.

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The Impact of Fractures on Survival in Multiple Myeloma: Results from a Population-Based Study

Blood ◽

10.1182/blood-2018-99-115403 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4490-4490

Author(s):

Sigrun Thorsteinsdottir ◽

Ingigerdur S Sverrisdottir ◽

Gauti Gislason ◽

Ola Landgren ◽

Ingemar Turesson ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Cox Regression ◽

Population Based ◽

Advisory Committees ◽

Population Based Study ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Introduction Multiple myeloma (MM) causes lytic bone lesions, osteopenia, and fractures, which increase the morbidity of MM patients. Results from small previous studies have indicated that fractures in MM have a negative effect on survival. Aims The aim of the study was to evaluate the impact of fractures on survival in MM patients diagnosed in Sweden in the years 1990-2013. Furthermore, to analyze the effect of bone fractures at MM diagnosis on subsequent survival. Methods Patients diagnosed with MM in 1990-2013 were identified from the Swedish Cancer Registry. Information on date of birth, diagnosis, and death were collected from the Registry of Total Population. Information on all fractures were retrieved from the Swedish Patient Registry. Cox regression model was used with fractures as time-dependent variables. The effect of fractures on survival was assessed for any fracture or a subtype of fracture (a specific bone fracture or ICD-coded pathologic fracture). Either first fracture or the first subtype of fracture was used in the analysis. The effect of a fracture at MM diagnosis (within 30 days before or 30 days after MM diagnosis) on survival was also estimated using a Cox regression model. All models were adjusted for age, sex, time of diagnosis, and previous fractures. Results A total of 14,008 patients were diagnosed with MM in the study period. A total of 4,141 (29.6%) patients developed a fracture including fractures that occurred within a year before MM diagnosis and thereafter. Hereof 2,893 (20.7%) patients developed a fracture after MM diagnosis. The risk of death was significantly increased for patients that developed a fracture after the time of MM diagnosis with a hazard ratio (HR) of 2.00 (95% confidence interval (CI) 1.91-2.10) for all fractures combined. The risk of death was significantly increased for patients that developed all subtypes of fractures after MM diagnosis except ankle fractures. The risk of death was significantly increased for patients that developed pathologic fractures (HR=2.17; 95% CI 2.03-2.32), vertebral fractures (HR=1.73; 95% CI 1.61-1.87), hip fractures (HR=1.99; 95% CI 1.82-2.18), femoral fractures (HR=2.62; 95% CI 2.32-2.98), humerus fractures (HR=2.57; 95% CI 2.32-2.86), forearm fractures (HR=1.24; 95% CI 1.05-1.46), and rib fractures (HR=1.52; 95% CI 1.31-1.77), but not for ankle fractures (HR 1.07; 95% CI 0.79-1.44). A total of 942 (6.7%) of all MM patients were diagnosed with a fracture within 30 days before or 30 days after MM diagnosis. The patients with a fracture at diagnosis were at a significantly increased risk of death compared to those without (HR 1.31; 95% CI 1.21-1.41; Figure) Conclusions Our large population-based study, including over 14,000 patients diagnosed with MM in Sweden in the years 1990-2013, showed that MM patients that developed a fracture after the time of diagnosis were at twofold increased risk of dying compared to MM patients without a fracture. Furthermore, MM patients with a fracture at diagnosis had a 30% higher risk of dying compared to patients without a fracture. Our results indicate that fractures in MM reflect a more advanced disease at diagnosis and stress the importance of managing MM bone disease in all MM patients. Figure. Figure. Disclosures Landgren: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

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