Changes in Serum Free Light Chain Rather Than Intact Monoclonal Immunoglobulin Levels Predict Outcome with Therapy in Patients with Light Chain Amyloidosis.

Abstract Abstract 747 Background: Light chain amyloidosis is a monoclonal plasma cell proliferative disorder characterized by multiorgan deposition of monoclonal light chain derived amyloid fibrils. The diffuse organ infiltration by the amyloid fibrils leads to various AL related clinical features. Therapy of AL has been primarily aimed at elimination or control of the monoclonal plasma cells, thus decreasing the light chain available for amyloid formation. Assessment of response to therapy has been grouped into hematological response demonstrating elimination or reduction of the monoclonal population and organ response demonstrating actual improvement in its structure or function. Given the potentially long delay in observing organ improvement, hematological response has been the surrogate short term marker for long term outcome given the relatively rapid decline seen in the monoclonal protein with effective therapy, as well as studies showing improved long term outcome with a hematological response, especially complete response. However, conventional hematological response criteria give priority to the intact monoclonal protein rather than the light chain, which is the amyloidogenic protein. We hypothesized that a light chain response will correlate better with outcome than changes in the intact monoclonal protein levels. Methods: We identified 348 patients who had undergone stem cell transplant (SCT) for AL from among a large group of patients undergoing different treatments for AL, and in whom serial tests results were available. We identified the lowest value attained following SCT for various hematological response parameters (intact serum M-protein [MP], the difference between involved and uninvolved serum free light chain [FLC-diff], and urine M-protein [UP]) before an alternate therapy was instituted. We first estimated the best cutoff for the degree of change in each parameter that predicted 5-year survival from SCT. Cox proportional hazards model was used for multivariable analysis of factors influencing overall survival (OS). Results: We first examined the relative contribution of the MP and the FLC-diff on the overall survival following transplant. The best cutoff for reduction in FLC-diff to predict OS at 5 years from SCT was 88% if all patients were considered and 90% if only those with a baseline FLC diff > 7.5 mg/dL were considered. The best cutoff for MP reduction was 40% for 5 year survival for all patients and 67% for those with a baseline MP > 1.0 gm/dL. We then looked at the impact of FLC reduction and MP reduction in a multivariable analysis using OS as endpoint. For all patients, FLC reduction, but not MP reduction significantly impacted outcome, and results were similar when considering patients with MP>1.0 gm/dl and FLC-diff > 7.5 mg/dl at baseline. Among those with a baseline FLC-diff >7.5 mg/dL (n=125), the overall survival was 35 mos from SCT for those with less than 90% decrease in FLC-diff (45 pts) compared to not reached for those with at least 90% decrease (80 pts); P < 0.001 (Figure). Conclusions: The current study supports the notion that reductions in the free light chain parameters represent a more useful measure of hematological response that translates into better overall survival and possible better chance at organ improvement. A reduction in the FLC difference of 90% appears to correlate best with prolonged survival. Disclosures: Kumar: CELGENE: Research Funding; MILLENNIUM: Research Funding; BAYER: Research Funding; GENZYME: Research Funding; NOVARTIS: Research Funding. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lacy:celgene: Research Funding.

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Early Serum Free Light Chain Response after High-Dose Melphalan and Stem Cell Transplantation Predicts Hematologic Response in AL Amyloidosis

Blood ◽

10.1182/blood-2020-138500 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 26-26

Author(s):

Vanessa Fiorini Furtado ◽

Dina Brauneis ◽

Shayna Sarosiek ◽

Karen Quillen ◽

Vaishali Sanchorawala

Keyword(s):

Light Chain ◽

Research Funding ◽

Amyloid Fibrils ◽

Advisory Board ◽

Free Light Chain ◽

Light Chains ◽

High Dose ◽

Al Amyloidosis ◽

Serum Free Light Chain ◽

High Dose Melphalan

Introduction Immunoglobulin light chain (AL) amyloidosis is a rare disease caused by a clonal plasma cell dyscrasia producing monoclonal light chains that misfold and form amyloid fibrils which can deposit in a variety of tissues and organs. This deposition of amyloid fibrils can lead to progressive organ impairment, multi-organ failure, and death if left untreated. High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is known to improve patient outcomes with hematologic complete responses (CR) rates of 25-67%. Hematologic CR is currently defined as the absence of monoclonal protein in serum and urine by immunofixation electrophoreses and normal serum free light chain ratio (FLCR). Studies have shown that even among patients achieving a normal FLCR after initial therapy with HDM, persistent elevation of the involved FLC (hiFLC) predicts poor prognosis. Serum half-life of FLCs is approximately 2-6 hours, even with diminished glomerular filtration rates, and could be a tool for early treatment response evaluation. We sought to determine the extent to which early FLC responses after HDM/SCT predict hematologic complete response (CR) at 6 months. Methods We analyzed patients with AL amyloidosis who underwent HDM/SCT from 2012-2019 at Boston Medical Center. Exclusion criteria included death within 100 days, lack of FLC data at any time point, pre-SCT normal FLC concentrations and ratio, and chronic renal insufficiency (serum creatinine >1.3 mg/dL) with a normal FLC ratio. All subjects received a total of 140-200 mg/m2 melphalan IV in equally divided doses on days -3 and -2. Stem cells were infused on day 0. FLC measurements were obtained early in the peri-SCT period (< 1 month), at 6 months, and at 12 months after HDM/SCT. The patients were evaluated for response according to the consensus response criteria at 6 months. Statistical analysis to compare CR at 6 months and early post-SCT free light chain levels was performed by Chi-square with significance considered at p<0.05. Results Of the 113 patients with AL amyloidosis treated with HDM/SCT during the specified time period, 32 were excluded (4 died within 100 days of SCT, 15 had normal FLCs pre-SCT, 5 lacked data, and 8 had chronic renal insufficiency (Cr >1.3 mg/dL) with normal FLCR. A total of 81 subjects (females=30) were analyzed. Median follow-up from SCT was 27.6 months (range, 6-145). Median time of early post-SCT FLC measurement was 8 days (range, 7-30). Median age at diagnosis was 58 years (range 30-79) and the iFLC was lambda in 81.5% (n = 66) of patients. Median number of bone marrow plasma cells was 10% (range, 1-50). The mean absolute involved FLC was 196 mg/L ±221 prior to SCT, 60 mg/L ± 77 in the early post-SCT period, 92 mg/L ± 152 at 6 months post-SCT. In early post-SCT period, 39.5% (n=32) had iFLC <20 mg/L, 28% (n=16/57) had dFLC<10 mg/L, and 84% (n=48/57) had normal FLCR. Early post-SCT dFLC <10 mg/dL and early post-SCT iFLC <20 mg/L were statistically associated with prediction of hematologic CR at 6 months (p=0.025 and p=0.001, respectively). However, early post-SCT normal FLCR was not associated with predicting hematologic CR at 6 months. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of early post-SCT iFLC <20 mg/L, dFLC <10 mg/L and normal FLCR to predict hematologic CR at 6 months are presented in table 1. Conclusion This study concludes that achievement of dFLC <10 mg/L and iFLC <20 mg/L in the early post-SCT period is associated with prediction of hematologic CR at 6 months. Early post-SCT dFLC <10 mg/L could be considered a tool for early evaluation of treatment response following HDM/SCT in AL amyloidosis. Key words: immunoglobulin light chains; AL amyloidosis, HDM/SCT Disclosures Sarosiek: Spectrum: Research Funding. Sanchorawala:Caelum: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Proclara: Other: advisory board; Abbvie: Other: advisory board; UpToDate: Patents & Royalties; Oncopeptide: Research Funding; Regeneron: Other: advisory board; Caleum: Other: advisory board; Janssen: Research Funding.

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Phase I Study of a Novel Bcl-2 Inhibitor, at-101 in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)

Blood ◽

10.1182/blood-2019-128610 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3137-3137

Author(s):

Sikander Ailawadhi ◽

Victoria R. Alegria ◽

Salman Ahmed ◽

Betsy Laplant ◽

Alak Manna ◽

...

Keyword(s):

Clinical Trial ◽

High Risk ◽

Febrile Neutropenia ◽

Phase I ◽

Light Chain ◽

Clinical Benefit ◽

Research Funding ◽

Phase I Study ◽

Free Light Chain ◽

Monoclonal Protein

Background: The development of novel treatment strategies has extended the median survival of MM to nearly a decade but the disease remains incurable and relapse is inevitable. The Bcl-2 pathway is highly relevant to MM cell survival and can be mitigated therapeutically. AT-101 is a novel, orally available pan Bcl-2 inhibitor (Bcl-2, Bcl-xl, Mcl-1, and Bcl-w). Preclinical in vitro and in vivo studies showed that AT-101 enhanced cytotoxicity of lenalidomide-dexamethasone (Rd). We conducted a phase I study in RRMM patients to establish the effective dose of AT-101 with Ld as well as record safety and preliminary efficacy of this combination (NCT02697344). Methods: Key eligibility criteria included: RRMM with measurable disease (serum monoclonal protein ≥1.0 g/dL or urine monoclonal protein >200mg/24 hour or serum immunoglobulin free light chain >10mg/dL AND abnormal serum free light chain ratio). Patients must have received 1-3 prior treatment regimens and have an absolute neutrophil count ≥1.0 x 109, platelets 75 x 109, creatinine clearance ≥50 mL/min, and ECOG performance status ≤2. AT-101 dosing was designed to reach a maximum daily target of 20mg (Cohort 1; 10 mg PO QD, Cohort 2; 20 mg PO QD) utilizing a standard 3 +3 dose escalation design in combination with standard doses of Rd. Treatment was given as outpatient for a maximum of 12, 28-day cycles. For pharmacodynamic studies, AT-101 alone was given in cycle 1, with R (25 mg on days 1-21) and d (40 mg weekly) added cycle 2 onwards. Results: Enrolled patients (n=10) included 60% males with median age 68.5 years (range 55-75) and median time since MM diagnosis 4.5 years (range 0.6-8.3). MM ISS stage was II/III in 7 patients and 8/10 had high-risk cytogenetics with 4 each having del17p and 1q+. Only 1 patient had t(11;14).Patients had received median 2 prior lines of therapy (range 1-3), with 7 having had prior autologous stem cell transplant (ASCT) and the initial induction regimen being bortezomib (V), R and dexamethasone (d) (VRd) in 8, Rd in 1 and cyclophosphamide (C) with Vd (VCd) in 1 patient. At the time of study entry, 3 patients were R refractory while 2 were refractory to both, V and daratumumab (Dara). Median duration of treatment was 7.5 cycles (range 2-12) and 3 patients completed all planned 12 cycles of treatment. Among the evaluable patients, dose limiting toxicities (DLTs) at 20 mg daily dose of AT-101 with 25 mg of R and 40 mg weekly included one patient with grade 4 febrile neutropenia and grade 4 neutropenia lasting 9 days and one patient with grade 4 thrombocytopenia lasting 8 days. G3/4 adverse events (AEs) included atrial flutter (n=1), white blood cell count decrease (n=3), neutropenia (n=5), febrile neutropenia (n=1) and thrombocytopenia (n=2), and back pain (n=1) . No G3/4 non-hematological AEs were noted. Any grade non-hematologic AEs seen in at least 20% (n=2) patients included fatigue (n=9), neuropathy (n=6), nausea (n=3), diarrhea (n=5), constipation (n=3), and creatinine increased (n=2). No patients experienced tumor lysis syndrome. Overall response rate (ORR) was 44% (2 each with very good partial response, VGPR and PR) and clinical benefit rate (CBR) was 89% with 2 additional patients showing minor response (MR) and 2 experiencing stable disease (SD) (Fig 1). Patients with high-risk disease had an ORR of 43% and a CBR of 100%. Median progression-free survival (PFS) for all patients was 8.1 months. Correlative analysis from patients who showed an objective response to treatment revealed a significant increase in bone marrow Th-effector cells, NK cells and cytotoxic CD8+ T-cells along with a significant decrease in immunosuppressive T-regulatory and B-regulatory cells was noted after 1 complete cycle of the combination therapy (p<0.05, Fig 2). Conclusions: This is the first reported clinical trial combining a Bcl-2 inhibitor with immunomodulatory drugs (IMiDs) in MM. AT-101-Rd is a clinically active regimen with an ORR of 40% in predominantly high-risk RRMM patients with an acceptable toxicity profile. Additional patients with MM experienced clinical benefit despite refractory status to prior therapy in this early phase clinical trial. These early findings support the further investigation of AT-101 specifically, and Bcl-2 inhibitors in general, with IMiDs in patients with MM. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy. Chanan-Khan:Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding; AbbVie: Research Funding. OffLabel Disclosure: AT-101 is not currently FDA-approved for treatment of any condition.

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Normalization of the Serum Free Light Chain (FLC) Ratio Is Associated with Superior Overall Survival among Myeloma Patients Achieving Immunofixation Negative State: Results Support Incorporation of Serum FLC Ratio in Stringent CR Definition.

Blood ◽

10.1182/blood.v112.11.1692.1692 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1692-1692 ◽

Cited By ~ 4

Author(s):

Shaji Kumar ◽

Angela Dispenzieri ◽

Dirk Larson ◽

Colin Colby ◽

Robert Kyle ◽

...

Keyword(s):

Overall Survival ◽

Light Chain ◽

Median Overall Survival ◽

Free Light Chain ◽

Serum Free ◽

Monoclonal Protein ◽

Protein Levels ◽

Serum Free Light Chain ◽

Serum And Urine

Abstract Background: Traditionally response to therapy in multiple myeloma (MM) is based on changes in the serum and urine monoclonal protein by immunoelectrophoresis. Immunofixation allows for detection of small amounts of monoclonal protein that cannot be quantitated on immunoelectrophoresis. Serum immunoglobulin free light chain (FLC) assay allows for detection of unbound kappa and lambda free light chain and has allowed disease measurement in patients with oligosecretory myelomas and can potentially allow detection of low levels of tumor burden, below the threshold of the standard tests. We examined this hypothesis in patients who had obtained a negative immunofixation in serum and urine following treatment of their MM. Methods: For the purposes of the study, we included selected patients with MM who had measurable monoclonal (M) protein levels at baseline (defined as >1 gm/dL in the serum or >200 mg/24 hour in the urine or involved free light chain > 10 mg/dL) on protein electrophoresis; patients with non-secretory and oligo-secretory myeloma were excluded. We then identified patients who since 1995 had a negative immunofixation in the serum and urine, all done at the same time (within 30 days of each other). Baseline demographics and clinical characteristics; date of diagnosis, last follow up, and follow up status; serum and urine M protein levels at diagnosis; and results of serum and urine immunofixation, and serum free light chain (FLC) ratio within 30 days of the immunofixation were all collected from the existing databases. Results: Eighty-four patients met the criteria for the study, all of whom had measurable disease at baseline and subsequently achieved negative immunofixation in serum and urine. Among these, 46 patients (55%) also had a normal FLC ratio (K/L ratio; 0.26–1.65). Th median time from diagnosis to the documented immunofixation was 7.5 months (range, 1–157). The median overall survival from diagnosis among those with a normal FLC ratio along with negative immunofixation was not reached compared to 76 months for those with abnormal FLC ratio, P = 0.02. The median overall survival from the documentation of negative immunofixation was not reached for the group with normal FLC ratio compared to 46.5 months for those with an abnormal FLC, P = 0.03. Conclusion: Attainment of a normal FLC ratio at the time of serum and urine immunofixation negative status identifies a group of patients with better outcome. The presence of an abnormal FLC ratio likely represents persistence of the clonal population that is secreting none or very small amounts of monoclonal protein. The data presented here supports the inclusion of FLC measurements as part of response criteria for MM as has been done for the definition of stringent CR in the IMWG response criteria. Figure: Overall survival from diagnosis in patients with or with out a normal FLC ratio at the time of serum and urine immunofixation. Figure:. Overall survival from diagnosis in patients with or with out a normal FLC ratio at the time of serum and urine immunofixation.

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Bortezomib Versus Non-Bortezomib Based Treatment for Transplant Ineligible Patients with Light Chain Amyloidosis

Blood ◽

10.1182/blood.v128.22.3317.3317 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3317-3317 ◽

Cited By ~ 3

Author(s):

Surbhi Sidana ◽

Nidhi Tandon ◽

Angela Dispenzieri ◽

Morie A. Gertz ◽

Francis Buadi ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Light Chain ◽

Research Funding ◽

Free Light Chain ◽

Cardiac Response ◽

Organ Involvement ◽

Advisory Committees ◽

Light Chain Amyloidosis ◽

Bortezomib Treatment

Abstract Introduction: Chemotherapeutic options for patients with systemic light chain amyloidosis (AL) who are not transplant candidates include bortezomib based therapy, melphalan with dexamethasone, and less commonly, immunomodulatory drugs (IMiDs). However, prospective clinical trial data comparing these regimens are lacking. This study aims to compare efficacy of bortezomib-based treatment to other therapies. Methods: All patients with AL seen within 90 days of diagnosis at our institution over a 10-year period (2006 to 2015) who did not undergo a stem cell transplant were identified from our institutional database. Data pertaining to demographics, diagnosis, treatment and follow-up were extracted from electronic medical records. Analyses were carried out by chi-square and Fisher's exact test for categorical variables and Kruskal-Wallis and Wilcoxon rank sum test for ordinal and continuous variables. Progression free survival (PFS) is defined as time to death, progression requiring treatment change or relapse requiring re-institution of treatment. PFS and overall survival was analyzed via the Kaplan-Meier method. Results: Seven hundred and twenty five patients met the inclusion criteria, of which 38% (n=275) received bortezomib containing regimens and 62% (n=450) received non-bortezomib based therapies. Bortezomib was used with dexamethasone in 24% (n=67) patients; and with other drugs, most commonly cyclophosphamide, in 76% (n=208) patients. Non-bortezomib treatment regimens included melphalan-based treatment in the majority (92%, n=414) followed by IMiDs with steroids and other drugs (8%, n=36). Baseline variables similar in both groups and their distribution in the entire cohort was as follows: gender distribution (63.3% males, n=459), median age of diagnosis (66.3 years, range 32.2 to 93.6), type of involved free light chain (FLC) (lambda 73%, n=523) and median plasma cell burden (10%, range 0 to 91). Median difference between the involved and uninvolved free light chain (dFLC) was higher in the bortezomib group (29 mg/dL vs. 23 mg/dL; p=0.017). There was no difference in organ involvement. In the bortezomib group, organ involvement was as follows: cardiac (81%, n=219), renal (62%, n=168) and hepatic (18%, n=48). In the non-bortezomib group, the rates of organ involvement were similar: cardiac (78%, n=346), renal (57%, n=247) and hepatic (19%, n=85). Median duration of first line treatment was similar in the 2 groups, with 178 days in the bortezomib cohort and 187 days in the non-bortezomib cohort. Response rates are illustrated in Table 1. Rates of very good partial response (VGPR) or better response were higher in the bortezomib group (64 % vs. 54%, p=0.0002). Patients treated with bortezomib achieved VGPR faster with higher rates of VGPR or better response seen at 3 months (48% vs. 27%, p <0.0001) and 6 months (57% vs. 34%, p < 0.0001) after initiation of therapy compared to non-bortezomib treatment. Rates of organ response were similar amongst the 2 groups as shown in Table 1. However, median time taken to achieve a cardiac response was shorter in the bortezomib group (23 vs. 38 weeks, p=0.0026). In a multivariable model, bortezomib-based treatment and dFLC at diagnosis were predictors of VGPR. Relapse or progression requiring change in therapy was more common in patients treated with non-bortezomib based therapy (38%, n=143/372) compared to bortezomib-based treatment (28%, n=67/236); p =0.01). However, no difference in overall survival was observed in patients treated with bortezomib (2.2 years; 95% confidence interval (CI): 1.7 to 3.3) vs. non-bortezomib therapies (1.7 years; 95% CI: 1.3 to 2.5). Conclusion: Treatment with bortezomib-based regimens results in a deeper response including higher rates of early VGPR at 3 and 6 months from starting therapy. Moreover, these patients achieve cardiac response faster and have lower rate of relapse. However, no difference in overall survival was seen, which may be explained by subsequent use of bortezomib-based therapies in this population. Disclosures Dispenzieri: Celgene: Research Funding; Alnylam: Research Funding; pfizer: Research Funding; Jannsen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees. Kumar:Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; AbbVie: Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; BMS: Consultancy; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Array BioPharma: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Kesios: Consultancy; Glycomimetics: Consultancy.

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Serum free light chain measurements to reduce 24-h urine monitoring in patients with multiple myeloma with measurable urine monoclonal protein

American Journal of Hematology ◽

10.1002/ajh.25215 ◽

2018 ◽

Vol 93 (10) ◽

pp. 1207-1210 ◽

Cited By ~ 1

Author(s):

Marcella Tschautscher ◽

Vincent Rajkumar ◽

Angela Dispenzieri ◽

Martha Lacy ◽

Morie Gertz ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Free Light Chain ◽

Serum Free ◽

Monoclonal Protein ◽

Serum Free Light Chain

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Sarcopenia Is a Negative Prognostic Factor in Patients Undergoing Transarterial Chemoembolization (TACE) for Hepatic Malignancies

Cancers ◽

10.3390/cancers11101503 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1503 ◽

Cited By ~ 4

Author(s):

Loosen ◽

Schulze-Hagen ◽

Bruners ◽

Tacke ◽

Trautwein ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Muscle Mass ◽

Transarterial Chemoembolization ◽

Cox Regression ◽

Psoas Muscle ◽

Muscle Size ◽

Rapid Decline ◽

Term Outcome ◽

Long Term Outcome

: Background and Aims: While transarterial chemoembolization (TACE) represents a standard of therapy for intermediate-stage hepatocellular carcinoma (HCC) and is also routinely performed in patients with liver metastases, it is still debated which patients represent the ideal candidates for TACE therapy in terms of overall survival. Sarcopenia, the degenerative loss of skeletal muscle mass and strength, has been associated with an adverse outcome for various malignancies, but its role in the context of TACE has largely remained unknown. Here, we evaluated the role of sarcopenia on the outcome of patients undergoing TACE for primary and secondary liver cancer. Methods: The patients’ psoas muscle size was measured on axial computed tomography (CT) scans and normalized for the patients’ height squared. This value was referred to as the psoas muscle index (PMI). The PMI was correlated with clinical and laboratory markers. Results: While pre-interventional sarcopenia had no impact on the direct tumor response to TACE, sarcopenic patients with a pre-interventional PMI below our ideal cut-off value of 13.39 mm/m2 had a significantly impaired long-term outcome with a median overall survival of 491 days compared to 1291 days for patients with a high PMI. This finding was confirmed by uni- and multivariate Cox-regression analyses. Moreover, a progressive rapid decline in muscle mass after TACE was a predictor for an unfavorable prognosis. Conclusion: Our data suggest that sarcopenia represents a previously unrecognized prognostic factor for patients undergoing TACE therapy which might yield important information on the patients’ post-interventional outcome and should therefore be implemented into clinical stratification algorithms.

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RA02.08: SALVAGE LYMPHADENECTOMY FOR 14 PATIENTS OF ESOPHAGEAL CANCER AFTER DEFINITIVE CHEMORADIOTHRAPY

Diseases of the Esophagus ◽

10.1093/dote/doy089.ra02.08 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 22-22

Author(s):

Kazuki Odagiri ◽

Makoto Yamasaki ◽

Koji Tanaka ◽

Yasuhiro Miyazaki ◽

Tomoki Makino ◽

...

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Lymph Nodes ◽

Conflicts Of Interest ◽

Treatment Guideline ◽

Hospital Death ◽

Curative Surgery ◽

Term Outcome ◽

Long Term Outcome ◽

Salvage Lymphadenectomy

Abstract Background Salvage Lymphadenectomy is regarded as the only curative surgery to residual or recurrence lymph nodes of esophageal cancer after definitive chemoradiotherapy (dCRT). However, salvage lymphadenectomy is not described in the Japanese esophageal cancer treatment guideline because of little evidences for the safety and efficacy. Methods From January 2011 to December 2015, we performed 14 salvage lymphadenectomies to residual or recurrence LN of esophageal squamous cell carcinoma(ESCC) in Osaka University. We assessed postoperative complications and long-term outcome. Results Average age was 64 year-olds (SD: 5.2). Male: Female = 11: 3. cStage I: II-IV = 7: 7. Surgery to cervical LN were 11 patients and abdominal LN were 3 patients. Surgery to residual LN (res-LN) were 9 patients and recurrence LN (rec-LN) were 5 patients. rec-LN patient's median time to recurrence after dCRT was 14.3 months (10.2–29.3). 4 patients were performed lymphadenectomy resecting with adjacent organs, 3 patients were bronchus (trachea? ) and 1 patient was right subclavian artery. 4 patients had postoperative complication, two were pneumonia, one was pulmonary thrombosis and one was lymphorrhea, but there was no serious case (Clavien-Dindo Grade II or less). We didn’t have hospital death. Six of 14 patients had recurrence and died after salvage lymphadenectomy. Recurrence sites were 2 mediastinal lymph nodes and liver, lung, loco-regional and peritoneal. But no patients had recurrence of main tumor. 5-year overall survival rate was 51.1%. Median survival time in 9 patients, surgery to res-LN, was 18.9 months (10.4–132 months) and 5 patients, surgery to rec-LN, was 4.9 months (1.4–26.6 months). Surgery to res-LN patients were longer than rec-LN patients in overall survival after salvage lymphadenectomy (P = 0.395). There was no difference due to the difference in recurrence site of the cancer in overall survival after salvage lymphadenectomy. Conclusion Our data show salvage lymphadenectomy safety and effectiveness after dCRT. Salvage lymphadenectomy may extend the prognosis of patients with esophageal cancer after dCRT. Thus, salvage lymphadenectomy may be one of the treatment options for the patients with residual or recurrent, especially the former, lymph node after definitive CRT, although it is necessary to evaluate in many cases. Disclosure All authors have declared no conflicts of interest.

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P6406Platelet reactivity in Hepatitis C virus infected patients on dual antiplatelet therapy for acute coronary syndrome

European Heart Journal ◽

10.1093/eurheartj/ehz746.1001 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

F Scudiero ◽

R Valenti ◽

R Marcucci ◽

G D Sanna ◽

A M Gori ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Platelet Reactivity ◽

Multivariable Analysis ◽

Hcv Infection ◽

Term Outcome ◽

Long Term Outcome ◽

Coronary Syndrome

Abstract Background Coronary artery disease (CAD) has been recognized as a serious and potentially life-threatening complication of Hepatitis C Virus (HCV) infection. High on treatment platelet reactivity has been associated with high risk of ischemic events in patients with CAD, but data regarding the association with HCV infection are still lacking. Purpose We sought to assess platelet reactivity on dual anti-platelet therapy and long-term outcome of acute coronary syndrome (ACS) patients infected with HCV. Methods ACS patients infected with HCV were matched to ACS patients without HCV for age, sex, diabetes, hypertension and renal function. Primary and secondary study endpoints were the proportion of patients with high on treatment platelet reactivity (HTPR) and long-term outcomes, respectively. Results HCV-infected ACS patients had higher levels of platelet reactivity (ADP10-LTA: 56% ± 18% vs. 44% ± 22%; p=0.002; Arachidonic Acid-LTA: 25% ± 21% vs. 16% ± 15%; p=0.011) and higher rate of HTPR on clopidogrel and aspirin compared with non-HCV patients. Multivariable analysis demonstrated HCV-infection to be an independent predictor of HTPR. At follow-up, estimated major adverse clinical events (MACE: cardiac death, non fatal myocardial infarction and any revascularization) were 57% vs. 37%, p=0.006 in HCV-infected ACS and non-HCV, respectively. Also, TIMI major bleeding rates were higher in HCV-infected subjects (11% vs. 3%; p=0.043) as compared with non-infected patients. Platelet function according to HCV status Conclusions ACS patients with HCV infection have increased on treatment platelet reactivity, higher rate of HTPR, MACE and bleedings as compared with non-HCV patients.

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The Prognostic Role of the Surgical Margins in Squamous Vulvar Cancer: A Retrospective Australian Study

Cancers ◽

10.3390/cancers12113375 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3375

Author(s):

Ellen L. Barlow ◽

Michael Jackson ◽

Neville F. Hacker

Keyword(s):

Vulvar Cancer ◽

Multivariable Analysis ◽

Surgical Margin ◽

Hazard Ratio ◽

Primary Site ◽

Surgical Margins ◽

Remote Site ◽

Term Outcome ◽

Subdistribution Hazard ◽

Long Term Outcome

For the last 30 years at the Royal Hospital for Women, unifocal vulvar squamous cancers have been treated by radical local excision, aiming to achieve a histopathological margin of ≥8 mm, equating to a surgical margin of 1 cm. The need for a margin of this width has recently been challenged. We aimed to determine the long-term outcome following this conservative approach, and the relationship between vulvar recurrences and surgical margins. Data were obtained retrospectively on 345 patients treated primarily with surgery for squamous vulvar cancer between 1987 and 2017. Median follow-up was 93 months. Five-year disease-specific survival was 86%. Of 78 vulvar recurrences, 33 (42.3%) were at the primary site and 45 (57.7%) at a remote site. In multivariable analysis, a margin < 5 mm showed a higher risk of all vulvar (Hazard ratio (HR), 2.29; CI, 1.12−4.70), and primary site recurrences (subdistribution hazard ratio (SHR), 15.20; CI, 5.21−44.26), while those with a margin of 5 to <8 mm had a higher risk of a primary site recurrence (SHR, 8.92; CI, 3.26−24.43), and a lower risk of remote site recurrence. Excision margins < 8 mm treated by re-excision or radiation therapy had a significantly decreased risk of recurrence. Guidelines should continue to recommend a surgical margin of 1 cm.

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