scholarly journals Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Damy ◽  
P Elliott ◽  
B Gundapaneni ◽  
S See Tai ◽  
M.B Sultan ◽  
...  
Keyword(s):  
Median Survival ◽  
Free Acid ◽  
Funding Source ◽  
Private Company ◽  
Heart Transplants ◽  
Term Survival ◽  
Long Term Survival ◽  
All Cause Mortality ◽  
Amyloid Cardiomyopathy

Abstract Background The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), demonstrated that tafamidis was an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Tafamidis, at an 80 mg daily dose, was subsequently approved in several countries for the treatment of ATTR-CM. Patients who completed ATTR-ACT were eligible to enroll in an ongoing long-term extension study (LTE) which provides additional data on the long-term efficacy of tafamidis. Purpose To assess the long-term benefit of tafamidis in patients with ATTR-CM and to determine median survival times with treatment. Methods Patients with ATTR-CM who completed ATTR-ACT (in which they were randomized to tafamidis meglumine 80 mg, 20 mg or placebo for 30 months) could enroll in the ongoing LTE in which patients continued to be treated with the same dose of tafamidis or, if previously treated with placebo, were randomized to tafamidis meglumine 80 mg or 20 mg. Tafamidis free acid 61 mg is a new formulation (bioequivalent to tafamidis meglumine 80 mg) developed for patient convenience and all patients in the LTE transitioned to tafamidis free acid 61 mg as of 1 Aug, 2018. All-cause mortality (with heart transplant or cardiac mechanical assist device [CMAD] implantation counted as death) was assessed using a Cox proportional hazards model (as of 1 Aug, 2019). Patients treated with tafamidis meglumine 80 mg in ATTR-ACT and the LTE who transitioned to tafamidis free acid 61 mg (tafamidis 80/61 mg) were compared with patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE (placebo/tafamidis). Results There were a total of 176 tafamidis 80/61 mg patients and 177 placebo/tafamidis patients. Median treatment duration was 51.9 months with tafamidis 80/61 mg and 51.4 months with placebo/tafamidis. With tafamidis 80/61 mg, there were 75 (42.6%) all-cause deaths; consisting of 67 (38.1%) deaths, 6 (3.4%) heart transplants, and 2 (1.1%) CMAD implantations. With placebo/tafamidis, there were 108 (61.0%) all-cause deaths; consisting of 102 (57.6%) deaths and 6 (3.4%) heart transplants. There was a significant reduction of 41.1% in the risk of all-cause mortality with tafamidis 80/61 mg compared with placebo/tafamidis (hazard ratio [95% CI], 0.5888 [0.4370, 0.7931]; P=0.0004). Median survival time with placebo/tafamidis was 35.8 months but was not reached with tafamidis 80/61 mg. Conclusions Treatment with tafamidis significantly improves long-term survival in patients with ATTR-CM. The comparatively poorer survival in patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE highlights the importance of early diagnosis and treatment. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer.

scholarly journals Long-term survival after Carpentier-Edwards Perimount aortic valve replacement in Western Denmark: a multi-centre observational study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lytfi Krasniqi ◽  
Mads P. Kronby ◽  
Lars P. S. Riber
Keyword(s):  
Risk Factors ◽  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Significant Risk ◽  
Valve Prosthesis ◽  
Term Survival ◽  
Long Term Survival ◽  
All Cause Mortality

Abstract Background This study describes the long-term survival, risk of reoperation and clinical outcomes of patients undergoing solitary surgical aortic valve replacement (SAVR) with a Carpentier-Edwards Perimount (CE-P) bioprosthetic in Western Denmark. The renewed interest in SAVR is based on the questioning regarding the long-term survival since new aortic replacement technique such as transcatheter aortic-valve replacement (TAVR) probably have shorter durability, why assessment of long-term survival could be a key issue for patients. Methods From November 1999 to November 2013 a cohort of a total of 1604 patients with a median age of 73 years (IQR: 69–78) undergoing solitary SAVR with CE-P in Western Denmark was obtained November 2018 from the Western Danish Heart Registry (WDHR). The primary endpoint was long-term survival from all-cause mortality. Secondary endpoints were survival free from major adverse cardiovascular and cerebral events (MACCE), risk of reoperation, cause of late death, patient-prothesis mismatch, risk of AMI, stroke, pacemaker or ICD implantation and postoperative atrial fibrillation (POAF). Time-to-event analysis was performed with Kaplan-Meier curve, cumulative incidence function was performed with Nelson-Aalen cumulative hazard estimates. Cox regression was applied to detect risk factors for death and reoperation. Results In-hospital mortality was 2.7% and 30-day mortality at 3.4%. The 5-, 10- and 15-year survival from all-cause mortality was 77, 52 and 24%, respectively. Survival without MACCE was 80% after 10 years. Significant risk factors of mortality were small valves, smoking and EuroSCORE II ≥4%. The risk of reoperation was < 5% after 7.5 years and significant risk factors were valve prosthesis-patient mismatch and EuroSCORE II ≥4%. Conclusions Patients undergoing aortic valve replacement with a Carpentier-Edwards Perimount valve shows a very satisfying long-term survival. Future research should aim to investigate biological valves long-term durability for comparison of different SAVR to different TAVR in long perspective.

Benefits of tafamidis in patients with advanced transthyretin amyloid cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Rapezzi ◽  
A.V Kristen ◽  
B Gundapaneni ◽  
M.B Sultan ◽  
M Hanna
Keyword(s):  
Disease Severity ◽  
Nyha Class ◽  
Funding Source ◽  
Class Iii ◽  
Private Company ◽  
Risk Of Death ◽  
6Mwt Distance ◽  
All Cause Mortality ◽  
Amyloid Cardiomyopathy

Abstract Background In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis was shown to be an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Further assessment of the efficacy of tafamidis in patients with more advanced ATTR-CM would aid treatment decisions. Purpose To characterize the benefits of tafamidis in patients with advanced ATTR-CM. Methods In ATTR-ACT, ATTR-CM patients were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Efficacy outcomes included all-cause mortality and frequency of cardiovascular (CV)-related hospitalisations. Key secondary endpoints were change from baseline to Month 30 in 6MWT distance and KCCQ-OS score. Efficacy assessments in NYHA Class III patients at baseline (n=141) were a pre-specified analysis. In a post-hoc analysis, mortality and CV-related hospitalizations were assessed in all patients grouped into quartiles of increasing disease severity based on 6MWT distance at baseline. Longer-term all-cause mortality (as of 1 Aug 2019) was assessed in NYHA Class III patients utilizing data from ATTR-ACT patients who enrolled in a long-term, extension study (LTE) and continued treatment with higher dose tafamidis (n=55; median treatment duration 51.6 months); or, if previously treated with placebo, started tafamidis treatment (placebo/tafamidis; n=63 [50.1 months]). Results In advanced ATTR-CM patients (NYHA Class III), tafamidis reduced the risk of death (HR [95% CI] 0.837, [0.541, 1.295], P=0.4253), and the decline in 6MWT distance (LS mean [SE], 31.6 (22.1) m; P=0.1526) and KCCQ-OS score (LS mean [SE], 13.1 (5.0); P=0.0090), vs placebo. Paradoxically, there was a higher frequency of CV-related hospitalizations with tafamidis (RR [95% CI] vs placebo, 1.411 [1.048, 1.900]). In all patients by 6MWT quartile, CV-related hospitalizations/year with tafamidis and placebo increased with disease severity, with the exception that placebo-treated patients in the highest severity quartile had fewer CV-related hospitalisations (0.73) than those in the third quartile (0.92). Mortality with tafamidis and placebo increased, and was greater with placebo, in every quartile (Figure). Survival (NYHA Class III patients in ATTR-ACT and LTE) was improved with high dose tafamidis with longer term follow-up (HR vs placebo/tafamidis [95% CI], 0.6569 [0.4175, 1.0336]; P=0.0692). Conclusions These analyses, including longer-term follow-up, demonstrate that patients with advanced ATTR-CM benefit from tafamidis. The decrease in CV-related hospitalisations in more severe patients treated with placebo suggests that the comparatively greater hospitalisation frequency in NYHA Class III patients treated with tafamidis is a consequence of their lower mortality rate. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer

scholarly journals Lower plasma melatonin levels predict worse long-term survival in pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Z Cai ◽  
T Klein ◽  
L.W Geenen ◽  
L Tu ◽  
S Tian ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Funding Source ◽  
Cardiovascular Research ◽  
Term Survival ◽  
Long Term Survival ◽  
Treatment Naïve ◽  
Pulmonary Arterial ◽  
Endogenous Melatonin

Abstract Background Exogenous melatonin has been reported to be beneficial in the treatment of pulmonary hypertension (PH) in animal models. Multiple mechanisms may be involved, with melatonin exerting anti-oxidant and anti-inflammatory effects, as well as inducing vasodilation and cardio-protection. However, endogenous levels of melatonin in treatment-naïve pulmonary arterial hypertension (PAH) patients and their clinical significance are still unknown. Methods and results Plasma levels of endogenous melatonin were measured by liquid chromatography-tandem mass spectrometry in treatment-naïve PAH patients (n=43) and healthy controls (n=111). Melatonin levels were higher in PAH patients when compared with controls (Median 118.9 [IQR 109.3–147.7] versus 108.0 [102.3–115.2] pM, P&lt;0.001) (Figure 1A). The overall mortality was 26% (11/43) during a median long-term follow-up of 42 [IQR: 32–58] months. When PAH patients were stratified into 4 groups according to the quartiles of melatonin levels, the mortality from below 1st quartile to above 4th quartile was 55% (6/11), 10% (1/10), 0% (0/12), and 40% (4/10), respectively (Figure 1B). Kaplan-Meier analysis further showed that patients with melatonin levels below the 1st quartile (&lt;109.3 pM) had a worse long-term survival than patients with melatonin levels above the 1st quartile (Mean survival times were 46 [95% CI: 30–65] versus 68 [58–77] months, Log-rank, p=0.026) (Figure 1C). Conclusion Endogenous melatonin levels were increased in treatment-naïve PAH patients, and lower levels of melatonin were associated with worse long-term survival in patient with PAH, however, whether exogenous melatonin supplements may be effective as a therapeutic strategy in human PAH remains to be established. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): This work was supported by the China Scholarship Council (201606230252) as well as the Netherlands CardioVascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-11, RECONNECT), and German Center for Cardiovascular Research (DZHK81Z0600207). Instrumentation support was received from AB Sciex, ltd. for LC-MS/MS analyses performed in this study.

EXTH-13. LOCAL DELIVERY OF AN IL-15 SUPERAGONIST USING A REPLICATING RETROVIRUS SIGNIFICANTLY IMPROVES SURVIVAL AND LYMPHOCYTE INFILTRATION IN POORLY IMMUNOGENIC MURINE GLIOBLASTOMA MODELS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi166-vi166
Author(s):  
Alexander Haddad ◽  
Jordan Spatz ◽  
Megan Montoya ◽  
Sara Collins ◽  
Sabraj Gill ◽  
...  
Keyword(s):  
T Cell ◽  
Median Survival ◽  
T Cell Activation ◽  
Term Survival ◽  
Long Term Survival ◽  
Immunosuppressive Cell ◽  
Imaging Results ◽  
Local Immunosuppression ◽  
Inflammatory Changes

Abstract Glioblastoma (GBM) leads to severe systemic and local immunosuppression, and immunotherapies have had limited clinical success. Here, we evaluated the treatment efficacy of RLI, a superagonist of T-cell activator IL-15, delivered to tumor cells using a tumor-selective retroviral replicating vector (RRV) in the syngeneic murine SB28 and Tu2449 GBM models, which are both engineered to be poorly immunogenic with low-mutational burden and known resistance to immunotherapy, and hence more accurate biomimetic models of human GBM. RRV-RLI replicated and spread effectively in cultured murine GBM cells with robust production of functional RLI (165.4 ± 5.3 ng/mL). Stereotactic injection of RRV-RLI into pre-established intracerebral SB28 tumors significantly reduced tumor growth on bioluminescent imaging, and increased median survival compared to control mice (55 vs. 19 days, p=0.002), leading to long-term survival in 12% of treated mice. In the Tu2449 model, imaging results showed complete eradication of intracerebral tumors after RRV-RLI treatment, with long-term survival (median not reached) in &gt; 85% of treated mice, compared to a median survival of 12.5 days in control mice (p=0.001). RRV-RLI treated tumors showed significantly increased CD8 T-cell infiltration, without altering immunosuppressive cell populations. Similarly, broad anti-tumor inflammatory changes, including increased expression of genes involved in T-cell activation and killing, were observed in the NanoString nCounter platform using a 770-gene panel representing various immune cell types. Notably, RLI was not detected in the blood of treated mice, and tumor-localized RRV-RLI gene delivery showed no adverse systemic immune effects in either model. In summary, RRV-mediated RLI immunotherapy results in immunostimulatory and pro-inflammatory changes to the tumor microenvironment and achieves a significant survival benefit in two poorly immunogenic syngeneic murine models of GBM. This tumor-localized immunomodulatory gene therapy has the potential to safely reverse the T-cell depleted immunophenotype of GBM.

Relationship between frailty and all-cause mortality in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational research programme AF general long-term registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Proietti ◽  
M Vitolo ◽  
S Harrison ◽  
G.A Dan ◽  
A.P Maggioni ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Frailty Index ◽  
Primary Study ◽  
Funding Source ◽  
Private Company ◽  
Kaplan Meier ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Introduction Frailty is a major health determinant for cardiovascular disease. Thus far, data on frailty in patients with atrial fibrillation (AF) are limited. Aims To evaluate frailty in a large contemporary cohort of European AF patients, the relationship with oral anticoagulant (OAC) prescription and with risk of all-cause death. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. A 38-items frailty index (FI) was derived from baseline characteristics according to the accumulation of deficits model proposed by Rockwood and Mitnitsky. All-cause mortality was the primary study outcome. Results Out of the 11096 AF enrolled patients, data for evaluating frailty were available for 6557 (59.1%) patients who have been included in this analysis (mean [SD] age 68.9 [11.5], 37.7% females). Baseline median [IQR] CHA2DS2-VASc and HAS-BLED were 3 [2–4] and 1 [1–2], respectively. At baseline, median [IQR] FI was 0.16 (0.12–0.23), with 1276 (19.5%) patients considered “not-frail” (FI&lt;0.10), 4033 (61.5%) considered “pre-frail” (FI 0.10–0.25) and 1248 (19.0%) considered “frail” (FI≥0.25). Age, female prevalence, CHA2DS2-VASc and HAS-BLED progressively increased across the FI classes (all p&lt;0.001). Use of OAC progressively increased among FI classes; after adjustments FI was not associated with OAC prescription (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.98–1.19 for each 0.10 FI increase). Conversely, FI was directly associated with vitamin K antagonist (VKA) use (OR: 1.26, 95% CI: 1.18–1.34 for each 0.10 FI increase) and inversely associated with non-VKA OACs (NOACs) use (OR: 0.82, 95% CI: 0.77–0.88). FI was significantly correlated with CHA2DS2-VASc (Rho= 0.516, p&lt;0.001). Over a median [IQR] follow-up of 731 [704–749] days, there were 569 (8.7%) all-cause death events. Kaplan-Meier curves [Figure] showed an increasing cumulative risk for all-cause death according to FI categories. A Cox multivariable analysis, adjusted for age, sex, type of AF and use of OAC, found that increasing FI as a continuous variable was associated with an increased risk of all-cause death (hazard ratio [HR]: 1.56, 95% CI: 1.40–1.73 for each 0.10 FI increase). An association with all-cause death risk was found across the FI categories (HR: 1.71, 95% CI: 1.23–2.38 and HR: 2.88, 95% CI: 2.02–4.12, respectively for pre-frail and frail patients compared to non-frail ones). FI was also predictive of all-cause death (c-index: 0.660, 95% CI: 0.637–0.682; p&lt;0.001). Conclusions In a European contemporary cohort of AF patients the burden of frailty is significant, with almost 1 out of 5 patients found to be “frail”. Frailty influenced significantly the choice of OAC therapy and was associated with (and predictive of) all-cause death at follow-up. Kaplan-Meier Curves Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies have supported it with unrestricted grants.

scholarly journals Patient Age and Survival After Surgery for Esophageal Cancer

2020 ◽  
Vol 28 (1) ◽  
pp. 159-166 ◽  
Author(s):  
Jesper Lagergren ◽  
Matteo Bottai ◽  
Giola Santoni
Keyword(s):  
Esophageal Cancer ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival ◽  
Flexible Parametric Model ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Disease Specific Mortality ◽  
Disease Specific

Abstract Background Esophagectomy for esophageal cancer is associated with a substantial risk of life-threatening complications and a limited long-term survival. This study aimed to clarify the controversial questions of how age influences short-term and long-term survival. Methods This population-based cohort study included almost all patients who underwent curatively intended esophagectomy for esophageal cancer in Sweden in 1987–2010, with follow-up through 2016. The exposure was age, analyzed both as a continuous and categorical variable. The probability of mortality was computed using a novel flexible parametric model approach. The reported probabilities are proper measures of the risk of dying, and the related odds ratios (OR) are therefore more suitable measures of association than hazard ratios. The outcomes were 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality. A novel flexible parametric model was used to derive the instantaneous probability of dying and the related OR along with 95% confidence intervals (CIs), adjusted for sex, education, comorbidity, tumor histology, pathological tumor stage, and resection margin status. Results Among 1737 included patients, the median age was 65.6 years. When analyzed as a continuous variable, older age was associated with slightly higher odds of 90-day all-cause mortality (OR 1.05, 95% CI 1.02–1.07), 5-year all-cause mortality (OR 1.02, 95% CI 1.01–1.03), and 5-year disease-specific mortality (OR 1.01, 95% CI 1.01–1.02). Compared with patients aged < 70 years, those aged 70–74 years had no increased risk of any mortality outcome, while patients aged ≥ 75 years had higher odds of 90-day mortality (OR 2.85, 95% CI 1.68–4.84), 5-year all-cause mortality (OR 1.56, 95% CI 1.27–1.92), and 5-year disease-specific mortality (OR 1.38, 95% CI 1.09–1.76). Conclusions Patient age 75 years or older at esophagectomy for esophageal cancer appears to be an independent risk factor for higher short-term mortality and lower long-term survival.

Peritoneal Colorectal Carcinomatosis Treated With Surgery and Perioperative Intraperitoneal Chemotherapy: Retrospective Analysis of 523 Patients From a Multicentric French Study

2010 ◽  
Vol 28 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Dominique Elias ◽  
François Gilly ◽  
Florent Boutitie ◽  
François Quenet ◽  
Jean-Marc Bereder ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Median Survival ◽  
Intraperitoneal Chemotherapy ◽  
Combined Treatment ◽  
Prognostic Impact ◽  
Term Survival ◽  
Multicentric Study ◽  
Long Term Survival ◽  
French Speaking

Purpose Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. Patients and Methods A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. Conclusion This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.

Relapse Rate and Long-Term Survival of AL Amyloidosis Patients Treated with High-Dose Melphalan and Autologous Stem Cell Transplantation (HDM/SCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3094-3094
Author(s):  
David C. Seldin ◽  
Martha Skinner ◽  
Betul Oran ◽  
Karen Quillen ◽  
Kathleen T. Finn ◽  
...  
Keyword(s):  
Median Survival ◽  
Plasma Cell ◽  
Relapse Rate ◽  
Long Term Results ◽  
High Dose ◽  
Al Amyloidosis ◽  
Term Survival ◽  
Long Term Survival ◽  
Early Results

Abstract AL amyloidosis is a plasma cell dyscrasia in which clonal immunoglobulin light chains misfold and are deposited in tissues, leading to organ failure in untreated patients, with median survival of only ~1 year. Oral melphalan and prednisone is minimally effective for the disease, with an increase in median survival to ~1.5 years, and a low rate of hematologic complete responses (CRs). Twelve years ago, we began treating patients with AL amyloidosis with HDM/SCT. In the plasma cell malignancy multiple myeloma, this approach produces hematologic CRs and improves survival, but is not curative, as all patients eventually relapse. In AL amyloidosis, the relapse rate and long-term survival have not been studied, but early results are promising, with most centers reporting CR rates of ~40% and excellent survival in responding patients. To address the durability and long-term results of treatment with HDM/SCT, here we report on the outcome for AL amyloidosis patients treated at Boston Medical Center with HDM/SCT >10 years ago. The first autologous transplant took place on July 18, 1994 in two years, by July 18, 1996, 43 patients with AL amyloidosis without myeloma or other hematologic disease had been treated with HDM/SCT, receiving 100–200 mg/m2 melphalan depending upon age and protocol. Of the 43 patients treated in this 2 yr period, 76% of the patients were male, 81% had a lambda monoclonal disease, and their median age was 52 (range, 29–71). In these first 43 patients, the 100 day peri-transplant mortality rate was 16%. Nineteen of the 43 patients (44%) achieved a hematologic CR after treatment. In annual followup, 4 of 19 patients (21%) eventually relapsed. Fourteen of 43 patients (33%) are still alive; 12 of 19 patients who achieved a CR (63%) are still alive, while only 2 of 34 patients who did not (6%) are still alive. Although there were fewer (8) patients with kappa clonal disease, they had a better outcome, with an 87% CR rate vs. 34% for lambda (P=0.006); 75% of the kappa patients are still alive, vs. 23% of the lambda patients (P=0.005). The median survival of all 43 patients is 4.7 years. Thus, treatment of AL amyloidosis patients with HDM/SCT produces a high CR rate that is durable and is associated with excellent 10 year survival, particularly for those patients achieving a hematologic CR and for patients with kappa clonal disease. Ongoing clinical trials of HDM/SCT, along with strategies to reduce morbidity and mortality and to improve the CR rate, incorporating additional cycles of HDM/SCT or new anti-plasma cell agents, appear to be well-justified by these results.

Long-term survival in patients with peritoneal metastasized gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 390-390
Author(s):  
Andreas Brandl ◽  
Yutaka Yonemura ◽  
Olivier Glehen ◽  
Paul H. Sugarbaker ◽  
Beate Rau
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Median Survival ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastasis ◽  
Tumor Recurrence ◽  
Term Survival ◽  
Long Term Survival ◽  
Crs And Hipec

390 Background: Peritoneal metastasis of gastric cancer is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in median survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyze a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. Methods: We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven peritoneal metastasis of gastric cancer, treated with CRS and HIPEC, and overall survival > 5 years. Patient, tumor, and therapeutic details were collected and analyzed. Results: A total of 29 patients with a mean age of 52.5 years and a mean PCI of 3.2 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and low PCI (PCI < 6) were present in 23/29 patients. 13/29 patients developed at a median of 82.2 months tumor recurrence. Tumor recurrence was associated with inferior median overall survival compared to patients without tumor recurrence (8.8 years vs. not reached; p = 0.002). Conclusions: Long-term survival and even cure are possible in patients with peritoneal metastasis of gastric cancer treated with CRS and HIPEC. Completeness of cytoreduction (CC-0) and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.

scholarly journals MO516A STRUCTURED EXPERT ELICITATION TO INFORM AND VALIDATE MORTALITY EXTRAPOLATIONS FOR A COST-EFFECTIVENESS ANALYSIS OF DAPAGLIFLOZIN

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Bartholomeus Willigers ◽  
Mario Ouwens ◽  
Andrew Briggs ◽  
Oliver Darlington ◽  
Purav Bhatt ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Expert Elicitation ◽  
Mortality Data ◽  
Term Survival ◽  
Long Term Survival ◽  
Literature Searches ◽  
All Cause Mortality ◽  
Elicitation Process ◽  
Study Population

Abstract Background and Aims Elevated albuminuria in patients with chronic kidney disease (CKD) is associated with increased risks of CKD progression, cardiovascular events and all-cause death. In the DAPA-CKD study, dapagliflozin significantly reduced the risk of all-cause death in patients with elevated albuminuria compared with placebo (hazard ratio: 0.69; 95% confidence interval 0.53–0.88). To assess the cost-effectiveness of new treatments, decision makers require survival estimates over a longer period than that of a typical clinical trial, usually over a lifetime time horizon. A formal elicitation process is currently underway to obtain estimates of long-term survival of patients with albuminuric CKD from clinical experts. Their responses will be used to validate extrapolations of all-cause mortality data from DAPA-CKD, which could inform cost-effectiveness analyses for dapagliflozin. Method Targeted literature searches were conducted to collate data on all-cause mortality in patients with CKD and elevated albuminuria. Clinical trials and observational studies were included if they involved non-dialysis-dependent patients with CKD aged 18 years and over, had more than 500 participants per study arm and reported incidence of all-cause death and/or all-cause mortality/survival Kaplan–Meier (KM) curves. To estimate long-term survival, KM curves were extrapolated to 20 years by calculating standard mortality ratios (SMRs) using age- and sex-adjusted general-population lifetable data. Study and patient characteristics and mortality data from relevant studies were provided to clinical experts to inform their judgements in a formal elicitation process. After receiving training on the elicitation process, six leading disease area experts were invited to complete the elicitation survey using an Excel-based tool, which consisted of 10 calibration questions, and three questions regarding the survival of patients in the placebo arm of the DAPA-CKD study at 10 and 20 years. The elicited estimates will be weighted and aggregated using Cooke’s method. Results Literature searches identified 13 relevant articles (seven clinical trials and six observational studies), with a range of 1094 to 5674 participants. Mean age varied across studies (range: 55–70 years). Where reported, median follow-up was 9–144 months, and mean estimated glomerular filtration rate (eGFR) at baseline was 22.4–56.3 mL/min/1.73 m2. Five studies exclusively included patients with type 2 diabetes (T2D). The incidence of all-cause death was reported in nine studies and was 1.5–9.4 deaths per 100 patient-years, with the highest incidence observed in a study reporting data for patients with CKD stage 4 and 5 (8.0 and 9.4 deaths per 100 patient-years, respectively). Nine studies provided KM curves; from these, estimated survival at 2 years ranged from 86% (study population mean age 67 years, eGFR &lt; 15 mL/min/1.73 m2) to 98% (study population mean age 58 years, mean eGFR 46.2 mL/min/1.73 m2). The SMR-extrapolated survival at 10 and 20 years was 36–80% and 2–69%, respectively. The ranges defined by the expert judgements collected to date for survival at 10 and 20 years are in line with the variability of the extrapolated KM survival curves. The elicitation process is ongoing and therefore, to avoid biasing the judgements that remain to be collected, preliminary results are not reported here. Results of the expert elicitation will be presented in full at the congress. Conclusion Initial results from the survey calibration questions suggest that the expert elicitation process provides expert judgements that are both informative and precise. The elicitation of survival estimates for patients with CKD and elevated albuminuria at 10 and 20 years will provide greater insight than extrapolated data alone, and will increase the validity of long-term survival projections for dapagliflozin cost-effectiveness analyses.

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