Benefit In Terms Of Survival Research Articles

Unresectable Ovarian Cancer Requires a Structured Plan of Action: A Prospective Cohort Study

Patients with unresectable disease during cytoreductive surgery (CRS) for advanced-stage ovarian cancer are underreported. Knowledge of treatment and survival after surgery is limited. The aim of this study is to address the knowledge gap about postoperative treatment and survival of patients whose surgery was abandoned due to unresectability after abdominal exploration. Women with FIGO stage IIIB-IV epithelial ovarian cancer whose disease was considered to be unresectable during surgery were included in this prospective study, a post hoc analysis of the PlaComOv study. The unresectable disease was defined as the inability to achieve at least suboptimal CRS without attempted CRS after careful inspection of the entire abdomen. Preoperative clinical data, perioperative findings, postoperative treatment and survival data were analyzed. From 2018 to 2020, 27 patients were included in this analysis. Treatment ranged from the cessation of treatment to one or several lines of chemotherapy with or without maintenance therapy. The median overall survival was 16 (IQR 5-21) months (95%CI 14-18). At 24 months of follow-up, four patients (15%) were alive. This study indicated a two-year survival of 15%. Optimal treatment strategies in terms of survival benefits are still ill-defined. Further study of this specific group of patients is warranted. We advocate an (inter)national registry of patients with unresectable cancer and comprehensive follow-up.

Gilteritinib Maintenance Therapy Post-Allogenic Stem-Cell Transplantation Improves the Prognosis of Patients with FLT3-Mutated AML

Introduction FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) and -tyrosine kinase domain (TKD) mutation were common mutations in acute myeloid leukemia (AML). FLT3-ITD mutation adversely affected the outcome of hematopoietic stem-cell transplantation (SCT). While sorafenib and midostaurin as maintenance therapy after SCT prolonged relapse-free and overall survival (OS), there are very few reports of post-transplant gilteritinib maintenance therapy outside of clinical trials. Hence, to explore the efficacy of the gilteritinib maintenance therapy post-SCT, we here report the prognostic impact of post-SCT gilteritinib maintenance in a clinical setting. Methods We retrospectively analyzed 25 FLT3-mutated relapsed or refractory AML patients who received allogeneic SCT at our center from January 1, 2011 to April 30, 2022. FLT3 mutation was analyzed by a commonly used polymerase chain reaction (PCR)-based assay. Measurable residual disease (MRD) was assessed by Wilms tumor 1 (WT1) mRNA expression in peripheral blood, and MRD positivity was defined as WT-1 >50 copies/μg in this study. Relapse was defined as an increase of 5% blasts or more. Non-relapse mortality (NRM) was defined as death without relapse. Leukemia-free survival (LFS) was defined as the time from transplantation to leukemia relapse or death from any cause, which comes first. OS was defined as the time from transplantation to death from any cause. Results The median age was 52 years. Twenty-two patients had ITD mutation and 5 had TKD mutation (2 had both ITD and TKD mutation). At the time of the transplant, 20 patients were in remission (6 were MRD-negative and 14 were MRD-positive) and five were in non-remission. All patients achieved hematologic complete remission (CR) after SCT and no patients relapsed within 30 days post-SCT. After hematological engraftment, 14 patients started to receive gilteritinib as maintenance therapy and 11 patients did not. Between the two groups, the patients' characteristics including disease status at transplant, SCT procedures, and donor sources were well balanced except for the administration of FLT3-inhibitor prior to SCT (100% in patients with gilteritinib maintenance and 45.5% in those without gilteritinib maintenance, p = 0.003). Eleven patients (78.6%) in the gilteritinib group and eight (72.7%) patients in the non-gilteritinib group had residual MRD in hematological CR or were non-CR prior to SCT. The median time from SCT to the initiation of gilteritinib was 36 days. The median dose at gilteritinib initiation was 40mg (range 20-120 mg). One patient developed grade 2 skin acute graft-versus-host disease (GVHD) after gilteritinib administration and 4/14 patients (28.6%) developed moderate-severe chronic GVHD (cGVHD, two developed pulmonary cGVHD, one eye and mouse, and one skin) with a median onset of 10.5 months (range 3.1-30.5 months), while only one patient temporary discontinued gilteritinib until the improvement of cGVHD. Late engraftment failure during gilteritinib maintenance was not observed. In terms of survival benefit, patients with gilteritinib maintenance showed significantly longer LFS and OS than those without gilteritinib (1-y LFS; 100% vs. 36.4%, 95% CI; 100-100% vs. 11.2-62.7%, p = 0.0028, Figure A, and 1-y OS; 100% vs. 45.5%, 95% CI; 100-100% vs. 16.7-70.7%, p = 0.0075, Figure B). The cumulative incidence of AML relapse at one-year in patients with gilteritinib maintenance group was significantly lower than those without (0% vs. 51.5%, 95% CI; 0-0% vs. 24.9-86.0%, p = 0.005). Especially, among patients with MRD positive or non-CR prior to SCT (n=19), patients who received gilteritinib maintenance showed a lower cumulative incidence of AML relapse at one-year than those without gilteritinib maintenance (0% vs. 68.8%, 95% CI; 0-0% vs. 35.9-95.2%, p = 0.0028, Figure C). Patients without MRD prior to SCT did not relapse with or without gilteritinib maintenance. These results suggest that gilteritinib maintenance therapy contributes to preventing post-transplant relapse in patients who remain MRD positive at the time of SCT. Conclusion Gilteritinib maintenance therapy post-SCT showed survival benefit in a clinical setting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 15666: Survival Benefit of Implantable Cardioverter Defibrillators in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Introduction: The effectiveness of implantable cardioverter-defibrillators (ICDs) in reducing mortality in patients with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is debated.Hypothesis. The ICD confers survival benefit in patients with CPVT. Methods: We included n=238 genotype-proven CPVT patients, of whom 91 (38%) had an ICD implanted. All patients were treated with beta-blocker (BB) monotherapy. Survival probability at the occurrence of a first Life-threatening Arrhythmic Event (LAE, defined as: sudden cardiac death, aborted cardiac arrest or hemodynamically non-tolerated ventricular tachycardia) was compared between ICD carriers and non-ICD carriers. In ICD carriers, the benefit-to-harm ratio (rate of appropriate shocks on LAE over rate of major complications) was investigated. Results: During 1,643 person-years of follow-up, 35/238 (15%) patients experienced a first LAE on BB monotherapy (annual LAE rate 2.1%, 95%CI: 1.5-3.0%). Of the 35 individuals who experienced an LAE, 23 patients had an ICD when the LAE occurred, and all survived after ICD shock. Of the remaining 12 patients who were not carriers of an ICD, 4/12 (33%) died suddenly, 2/12 (17%) survived but suffered anoxic brain injury, while 6/12 (50%) survived without consequences. The probability of dying at the occurrence of a first LAE was 25-fold higher (OR: 24.9, 95% CI: 1.2-513.0; p=0.037) in patients without an ICD, as compared to patients with an ICD. Major complications occurred in 17/91 (19%) patients with an ICD (2.6% per year, 95%CI: 1.5%-4.1%). Comparing the rate of major complication to the rate of appropriate ICD shocks on LAE (LAE rate 5.2% per year, 95%CI: 3.5-7.4%), the benefit-to-harm ratio was 2, favoring the benefit of ICD therapy. Conclusion: The ICD conferred a significant survival benefit in terms of arrhythmic mortality at the occurrence of the first LAE in BB monotherapy.

Preclinical Experience of the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL) in Management of Acute Liver Failure

The Spheroid Reservoir Bioartificial Liver (SRBAL) is an innovative treatment option for acute liver failure (ALF). This extracorporeal support device, which provides detoxification and other liver functions using high-density culture of porcine hepatocyte spheroids, has been reported in three randomized large animal studies. A meta-analysis of these three preclinical studies was performed to establish efficacy of SRBAL treatment in terms of survival benefit and neuroprotective effect. The studies included two hepatotoxic drug models of ALF (D-galactosamine, α-amanitin/lipopolysaccharide) or a liver resection model (85% hepatectomy) in pigs or monkeys. The SRBAL treatment was started in three different settings starting at 12 h, 24 h or 48 h after induction of ALF; comparisons were made with two similar control groups in each model. SRBAL therapy was associated with significant survival and neuroprotective benefits in all three animal models of ALF. The benefits of therapy were dose dependent with the most effective configuration of SRBAL being continuous treatment of 24 h duration and dose of 200 g of porcine hepatic spheroids. Future clinical testing of SRBAL in patients with ALF appears warranted.

Threats to UK freshwaters under climate change: Commonly traded aquatic ornamental species and their potential pathogens and parasites

The aquatic ornamental industry, whilst providing socio-economic benefits, is a known introduction pathway for non-native species, which if invasive, can cause direct impacts to native species and ecosystems and also drive disease emergence by extending the geographic range of associated parasites and pathogens and by facilitating host-switching, spillover and spill-back. Although current UK temperatures are typically below those necessary for the survival and establishment of commonly-traded tropical, and some sub-tropical, non-native ornamental species, the higher water temperatures predicted under climate-change scenarios are likely to increase the probability of survival and establishment. Our study aimed primarily to identify which of the commonly-traded non-native ornamental aquatic species (fish and invertebrates), and their pathogens and parasites, are likely to benefit in terms of survival and establishment in UK waters under predicted future climate conditions. Out of 233 ornamental species identified as traded in the UK, 24 were screened, via literature search, for potential parasites and pathogens (PPPs) due to their increased risk of survival and establishment under climate change. We found a total of 155 PPPs, the majority of which were platyhelminths, viruses and bacteria. While many of the identified PPPs were already known to occur in UK waters, PPPs currently absent from UK waters and with zoonotic potential were also identified. Results are discussed in the context of understanding potential impact, in addition to provision of evidence to inform risk assessment and mitigation approaches.

S3206 Turmeric-Associated Liver Injury: The Yellow in Your Food Causing the Yellow in Your Skin

Introduction: Turmeric is a herbal medication that has gained significant popularity recently. Turmeric is used for its flavor, color, and purported antiinflammatory, antioxidant, antineoplastic, and antimicrobial properties. Turmeric supplements are generally self-medicated and patients can avail of them over the counter or through online portals. Turmeric typically has low bioavailability orally and is hence sometimes enhanced with nanoparticle delivery methods or piperine (black pepper) to increase absorption. Studies have linked these formulations to a higher incidence of hepatotoxicity. Case Description/Methods: A 55-year-old female with a past medical-only significant for alcohol use presented to the emergency room with jaundice. She stated that she drank about 2 glasses of wine daily for the past 30 years and five days before her admission she drank around 5 drinks during St’ Patrick’s Day. Vital signs were stable and scleral icterus was noted. Lab investigations showed an alanine transaminase (ALT) of 2143U/L, aspartate transaminase (AST) of 2025U/L, alkaline phosphatase (ALP) of 590U/L, total bilirubin 8.1mg/dL, direct bilirubin 6mg/dL, and INR of 1.2. On further questioning, she revealed that she had been taking turmeric supplements daily for the past month for wrist arthralgias. She was consuming Qunol turmeric 1500mg once daily. Ultrasound of the abdomen was normal. She was given 19,200mg of NAC over 24 hours and all her medications were held. Over the course of the next five days her ALT came down to 1,730U/L and her AST came down to 1,517U/L without any additional therapy and she was asymptomatic. An extensive workup including hepatitis viruses, cytomegalovirus, smooth muscle antibody, and ceruloplasmin was sent which were all negative. She was discharged with close outpatient monitoring and her liver function tests normalized over two months (Figure). Discussion: What makes our case unique is the use of NAC and quick discharge. There are few studies that have explored the role of NAC in the management of acute liver failure for non-acetaminophen-induced causes. The data is mixed with one Cochrane analysis showing no benefit in terms of death and need for a liver transplant. Another study shows that there may be a survival benefit in terms of post-transplant survival, transplant-free survival, and overall survival while decreasing the overall length of hospital stay. Through our case report, we hope to encourage clinicians to keep this etiology in mind when diagnosing acute liver enzyme elevations.Figure 1.: Turmeric.

Emerging insights of drug resistance in metastatic castration resistant prostate cancer.

In recent years, castration resistant prostate cancer patients therapeutic landscape has dramatically changed. The use of taxane-based chemotherapy, new generation hormone therapy, an immunotherapeutic agent Sipuleucel-T, an alpha-emitter Radium-223, and recently PARP-inhibitors has provided a consistent benefit in terms of survival and quality of life.

Is pelvic exenteration in the presence of liver metastases justified?

The presence of liver metastases in association with pelvic recurrence has been considered for a long period of time as the sign of systemic neoplastic impregnation and therefore, these patients were considered as candidates for palliative chemotherapy. However, in the last decades attention was focused on identifying patients who could benefit from surgery in such cases. The aim of the current paper is to discuss about the indications and contraindications of associating extended pelvic resections and liver resections in order to maximize the benefits in terms of survival for patients with advanced stage or recurrent rectal cancer.

Evaluation of abdominal compression–decompression combined with chest compression CPR performed by a new device: Is the prognosis improved after this combination CPR technique?

IntroductionThis study was designed to compare the outcomes of standard cardiopulmonary resuscitation (STD-CPR) and combined chest compression and abdominal compression–decompression cardiopulmonary resuscitation (CO-CPR) with a new device following out-of-hospital cardiac arrest (OHCA). Moreover, we investigated whether patient prognosis improved with this combination treatment.MethodsThis trial was a single-centre, prospective, randomized trial, and a blinded assessment of the outcomes was performed. A total of 297 consecutive patients with OHCA were initially screened, and 278 were randomized to the STD-CPR group (n = 135) or the CO-CPR group (n = 143). We compared the proportions of patients who achieved a return of spontaneous circulation (ROSC), survived to hospital admission and survived to hospital discharge. In addition, we also performed the Kaplan–Meier analysis with a log-rank test at the end of the follow-up period to compare the survival curves of the two groups.ResultsThe differences were not statistically significant in the proportion of patients who achieved ROSC [31/135 (23.0%) versus 35/143 (24.5%)] and survived to hospital admission [28/135 (20.7%) versus 33/143 (23.1%)] between the CO-CPR group and STD-CPR group. However, there was a significant difference in the proportion of patients who survived to hospital discharge [16/135 (11.9%) versus 7/143 (4.9%)] between the two groups. Nine patients (6.7%) in the CO-CPR group and 2 patients (1.4%) in the STD group showed good neurological outcomes according to the cerebral performance category (CPC) scale score, and the difference was statistically significant (P = 0.003). The Kaplan–Meier curves showed that the patients in the CO-CPR group achieved better survival benefits than those in the STD-CPR group at the end of the follow-up period (log-rank P = 0.007).ConclusionCO-CPR was more beneficial than STD-CPR in terms of survival benefits in patients who have suffered out-of-hospital cardiac arrest.Trial registration Chinese Clinical Trial Registry, registered number: ChiCTR2100049581. Registered 30 July 2021- Retrospectively registered. http://www.medresman.org.cn/uc/index.aspx.

Coronariografía urgente en los pacientes con parada cardiaca extrahospitalaria sin elevación del segmento ST. Ensayo clínico COUPE

Introduction and objectivesThe role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest (OHCA) in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. We aimed to assess whether emergency CAG and PCI would improve survival with good neurological outcome in this population. MethodsIn this multicenter, randomized, open-label, investigator-initiated clinical trial, we randomly assigned 69 survivors of OHCA without STEMI to undergo immediate CAG or deferred CAG. The primary efficacy endpoint was a composite of in-hospital survival free of severe dependence. The safety endpoint was a composite of major adverse cardiac events including death, reinfarction, bleeding, and ventricular arrhythmias. ResultsA total of 66 patients were included in the primary analysis (95.7%). In-hospital survival was 62.5% in the immediate CAG group and 58.8% in the delayed CAG group (HR, 0.96; 95%CI, 0.45-2.09; P=.93). In-hospital survival free of severe dependence was 59.4% in the immediate CAG group and 52.9% in the delayed CAG group (HR, 1.29; 95%CI, 0.60-2.73; P=.4986). No differences were found in the secondary endpoints except for the incidence of acute kidney failure, which was more frequent in the immediate CAG group (15.6% vs 0%, P=.002) and infections, which were higher in the delayed CAG group (46.9% vs 73.5%, P=.003). ConclusionsIn this underpowered randomized trial involving patients resuscitated after OHCA without STEMI, immediate CAG provided no benefit in terms of survival without neurological impairment compared with delayed CAG.ClinicalTrials.gov Identifier: NCT02641626Full English text available from:www.revespcardiol.org/en

A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma

PurposeThe role of concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) is still controversial. Our objective is to evaluate the value of concurrent chemotherapy in stage II NPC receiving radiotherapy (RT).MethodsWe searched the PubMed, Embase, and Scopus databases for studies comparing CCRT versus RT alone in stage II NPC with survival outcomes and toxicities, including locoregional recurrence-free survival (LRFS), metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and grade 3–4 acute toxicities. The hazard ratios (HRs) of survival outcomes and risk ratios (RRs) of toxicities were extracted for meta-analysis. Subgroup analysis for stage N1 patients was performed to further explore whether these populations can earn benefits from concurrent chemotherapy.ResultsNine eligible studies with a total of 4,092 patients were included. CCRT was associated with a better OS (HR = 0.61, 95% CI 0.44–0.82), LRFS (HR = 0.62, 95% CI 0.50–0.78), and PFS (HR = 0.65, 95% CI 0.54–0.79), but with similar DMFS (HR = 0.81, 95% CI = 0.46–1.45) compared with two-dimensional RT (2DRT) alone. However, CCRT showed no survival benefit in terms of OS (HR = 0.84, 95% CI 0.62–1.15), LRFS (HR = 0.85, 95% CI 0.54–1.34), DMFS (HR = 0.96, 95% CI 0.60–1.54), and PFS (HR = 0.96, 95% CI 0.66–1.37) compared with intensity-modulated RT (IMRT) alone. Subgroup analyses indicated that CCRT had similar OS (HR = 1.04, 95% CI 0.37–2.96), LRFS (HR = 0.70, 95% CI 0.34–1.45), DMFS (HR = 1.03, 95% CI 0.53–2.00), and PFS (HR = 1.04, 95% CI 0.58–1.88) in the stage N1 populations. Meanwhile, compared to RT alone, CCRT significantly increased the incidence of grade 3–4 leukopenia (RR = 4.00, 95% CI 2.29–6.97), mucositis (RR = 1.43, 95% CI 1.16–1.77), and gastrointestinal reactions (RR = 8.76, 95% CI 2.63–29.12). No significant differences of grade 3–4 toxicity in thrombocytopenia (RR = 3.45, 95% CI 0.85–13.94) was found between the two groups.ConclusionFor unselected patients with stage II NPC, CCRT was superior to 2DRT alone with better LRFS, PFS, and OS, while adding concurrent chemotherapy to IMRT did not significantly improve survival but exacerbated acute toxicities.Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022318253.

Modulation of mTOR Signaling in Cardiovascular Disease to Target Acute and Chronic Inflammation.

Inflammation is a key component in the pathogenesis of cardiovascular diseases causing a significant burden of morbidity and mortality worldwide. Recent research shows that mammalian target of rapamycin (mTOR) signaling plays an important role in the general and inflammation-driven mechanisms that underpin cardiovascular disease. mTOR kinase acts prominently in signaling pathways that govern essential cellular activities including growth, proliferation, motility, energy consumption, and survival. Since the development of drugs targeting mTOR, there is proven efficacy in terms of survival benefit in cancer and allograft rejection. This review presents current information and concepts of mTOR activity in myocardial infarction and atherosclerosis, two important instances of cardiovascular illness involving acute and chronic inflammation. In experimental models, inhibition of mTOR signaling reduces myocardial infarct size, enhances functional remodeling, and lowers the overall burden of atheroma. Aside from the well-known effects of mTOR inhibition, which are suppression of growth and general metabolic activity, mTOR also impacts on specific leukocyte subpopulations and inflammatory processes. Inflammatory cell abundance is decreased due to lower migratory capacity, decreased production of chemoattractants and cytokines, and attenuated proliferation. In contrast to the generally suppressed growth signals, anti-inflammatory cell types such as regulatory T cells and reparative macrophages are enriched and activated, promoting resolution of inflammation and tissue regeneration. Nonetheless, given its involvement in the control of major cellular pathways and the maintenance of a functional immune response, modification of this system necessitates a balanced and time-limited approach. Overall, this review will focus on the advancements, prospects, and limits of regulating mTOR signaling in cardiovascular disease.

P956: EMMY COHORT: MANAGEMENT OF NEWLY DIAGNOSED OR RELAPSED/ REFRACTORY MULTIPLE MYELOMA IN PATIENTS AGED OF 80 YEARS AND OVER

Background: Multiple myeloma (MM) patients aged 80 years and older are a population more prone to comorbidities, frailty, cognitive impairment or physical decline and require appropriate management of their myeloma. They are often underrepresented in pivotal clinical trials, with little data available on their management. The EMMY study is a large-scale epidemiological study to assess the epidemiology and real-life management of MM and can focus on the use and real-life efficacy of treatments for newly diagnosed or relapsed/ refractory elderly MM patients. Aims: To describe the management of MM in newly diagnosed or relapsed patients aged 80 years and over and to assess the real-life effectiveness of the treatments received. Methods: EMMY is a descriptive, multicenter, national, non-interventional study conducted in 72 IFM (Intergroupe Francophone du Myélome, sponsor) centers in France. Any patient initiating treatment for MM over a 3-month observation period, from October to December, is included, since 2017. It is a dynamic cohort with the inclusion of approximately 900 patients each year: 2765 patients included at the end of 2019 of which 561 were aged 80 and over (20.3%). Data are updated annually from hospital records up to 2020 at the time of the analysis. Four cohorts of patients aged 80 years and older were analysed according to the line of treatment initiated during their follow-up: L1, L2, L3 or L4+. Median time to next treatment (mTNT), median progression-free survival (mPFS) and median overall survival (mOS) were assessed in months(m). Results: Patients ≥80 years initiated 19.8% of L1s (237/1199) 22.7% (232/1022) of L2s, 22.2% (167/751) of L3s and 18.7% (288/1540) of L4+. They are 7.5% patients ≥85 years old to initiate L1, 8.7% L2, 7.4% L3 and 5.1% L4+. When the line is started, an ECOG ≥2 is reported for 39.4% of L1, 27.7% of L2, 35.1% of L3 and 38.5% of L4 patients and comorbidities recorded in 45.1% of L1, 39.6% of L2, 35.4% of L3 and 38.6% of L4+. In L1, the ISS is level I, II, III for 20.2%, 27.4% and 52.4% of patients. In L1, over the 2017-2020 study period, patients received treatment with PI (58.6%), IMID (32.1%), PI/IMID (4.2%), anti-CD38 (1.3%) or other molecules (3.8%). In L2, they received PI (22.8%), IMID (48.7%), PI/IMID (11.7%), anti-CD38 (14.2%) or other (2.6%), in L3 PI (12.6%), IMID (38, 9%), PI/IMID (9.6%), anti-CD38 (29.3%) or other (9.6%) and in L4+ a PI (23.3%), IMID (20.1%), PI/IMID (5.6%), anti-CD38 (29.2%) or other (21.9%). More than half received a double combination in L1 (50.2%), L2 (59.9%), L3 (54.4%) and L4+ (53.8%). Regarding efficacy, mTNT is 20.3m [15.2; 24.6] in L1, 14.7m [12.3; 20.4] in L2, 10.8m [9; 13.5] in L3 and 8.2m [6.5; 11.2] in L4+. The mPFS is 19.3m [15.1; 23.2] in L1, 12.6m [10.1; 17.5] in L2, 8.9m [10.1; 17.5] in L3 and 5.9m [4.5;7.4] in L4+. The mOS is not reached in L1 (rate at 30m: 76.7% [70; 83.3]) and L2 (rate at 30m: 58.1% [48.1; 68]; it is 25.7m [17.1; NE] in L3 and 18.3m [13.4; 22.4] in L4+. Summary/Conclusion: Patients ≥80 years of age account for more than 20% of de novo and relapsed myeloma patients treated in EMMY. Double combinations are used in half of the situations. Over the study period, PI-based treatments were preferred in L1, IMID-based in L2 and antiCD38 for 30% of patients in L3 and L4+. The benefits in terms of survival are real and this specific population is likely to increase significantly in the near future, requiring human and logistical resources.

Coronary angiography in patients without ST-segment elevation following out-of-hospital cardiac arrest. COUPE clinical trial

Introduction and objectivesThe role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest (OHCA) in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. We aimed to assess whether emergency CAG and PCI would improve survival with good neurological outcome in this population. MethodsIn this multicenter, randomized, open-label, investigator-initiated clinical trial, we randomly assigned 69 survivors of OHCA without STEMI to undergo immediate CAG or deferred CAG. The primary efficacy endpoint was a composite of in-hospital survival free of severe dependence. The safety endpoint was a composite of major adverse cardiac events including death, reinfarction, bleeding, and ventricular arrhythmias. ResultsA total of 66 patients were included in the primary analysis (95.7%). In-hospital survival was 62.5% in the immediate CAG group and 58.8% in the delayed CAG group (HR, 0.96; 95%CI, 0.45-2.09; P=.93). In-hospital survival free of severe dependence was 59.4% in the immediate CAG group and 52.9% in the delayed CAG group (HR, 1.29; 95%CI, 0.60-2.73; P=.4986). No differences were found in the secondary endpoints except for the incidence of acute kidney failure, which was more frequent in the immediate CAG group (15.6% vs 0%, P=.002) and infections, which were higher in the delayed CAG group (46.9% vs 73.5%, P=.003). ConclusionsIn this underpowered randomized trial involving patients resuscitated after OHCA without STEMI, immediate CAG provided no benefit in terms of survival without neurological impairment compared with delayed CAG.ClinicalTrials.gov Identifier: NCT02641626

Debulking surgery for metastatic endometrial cancer – a case report and literature review

Although endometrial cancer is usually diagnosed in early stages of the disease due to the frequent association of worrisome symptoms such as postmenopausal bleeding, in certain cases the patients are diagnosed when metastatic lesions are already present. In such cases, a multidisciplinary approach is needed in order to achieve a maximum benefit in terms of survival. The aim of the current paper is to report a 62 year old patient diagnosed with endometrial cancer with bone and pulmonary metastases in whom a complex oncological and surgical therapeutic strategy was performed with good results.

Abstract 2991: Survival reliability of Glioblastoma on CD38

Abstract Glioblastoma (GBM) is a fatal malignancy of the brain. Unfortunately, the current multimodality management approach does not lead to long term survival benefits. Several prognostic factors such as Blood Brain Barrier (BBB) & Blood Tumor Barrier (BTB), Glioma Stem-like Cells (GSCs), an immunosuppressive tumor microenvironment (TME) and genetic heterogeneity promotes GBM progression. To improve treatment efficacy, these factors should be addressed in a rational manner. Our pre-clinical investigations indicate that maintenance of CD38 expression, a type II transmembrane glycoprotein, is vital to GBM survival. CD38 could be an ideal biologically relevant target as it is homogeneously expressed on tumor cells and its TME elements. Furthermore, accessibility of FDA approved anti-CD38 therapies, non-overlapping toxicities and potential to cross the BBB has granted approval of our phase I study using Radiation/Temozolomide and Immunotherapy with Daratumumab to Improve Antitumor Efficacy in newly diagnosed Glioblastoma (PRIDE) (NCT04922723). In brief, we performed Western blot (WB), RT-qPCR, and flow cytometry to examine CD38 expression on human GBM cell lines and microglia (LN229, T98G, DI-321, SA21 and HMC3) including CD38 transfected cells. We used trans well assays to analyze changes in CD38 expression in several environments. MTS viability assay was used to study the viability of Temozolomide on GBM cells. Basal expression of CD38 on GBM cells was assessed, showing that CD38 expression varies amongst cell lines and components of its TME. CD38 negative (flow sorted) cells regain CD38 expression around Day 4 after sorting, indicating that CD38 is crucial for GBM survival. We then sorted cells into CD38 negative and positive and performed trans well experiments with overexpressing and knock down cells, revealing that CD38 expression changes based upon surrounding cells in its environment. Cells transfected with shRNA against CD38 have a slower proliferative rate compared to wild-type and CD38 overexpressing cells. We also saw that LN229 Temozolomide (TMZ) resistant (LN229-TR) cells also have a slower proliferative rate and show an increase in CD38 expression. We also observed that CD133, SOX2 and Nestin are significantly over expressed in LN229-TR compared to LN229 CD38 WT, while sharing similar CD38 expression as GSCs and malignant GBM cells. IC50 of TMZ on CD38 overexpressing cells was significantly higher than CD38 WT GBM cells suggesting that CD38 expression contributes towards treatment resistance. All experiments were performed in triplicate and p values less than 0.05 were considered significant. Our preliminary data suggests that CD38 is regulating the proliferation rate as well as stem cell like features of GBM cells. Moreover, overexpression of CD38 is leading to TMZ resistance in pre-clinical models. Our ongoing in vitro and in vivo gene deletion experiments will further solidify the biological importance of CD38 in GBM. Citation Format: Leland Earp, Srishti Kala, Sonikpreet Aulakh. Survival reliability of Glioblastoma on CD38 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2991.

Management of incidentally discovered appendiceal neuroendocrine tumors after an appendicectomy.

Appendiceal neuroendocrine tumors (aNETs) are an uncommon neoplasm that is relatively indolent in most cases. They are typically diagnosed in younger patients than other neuroendocrine tumors and are often an incidental finding after an appendectomy. Although there are numerous clinical practice guidelines on management of aNETs, there is continues to be a dearth of evidence on optimal treatment. Management of these tumors is stratified according to risk of locoregional and distant metastasis. However, there is a lack of consensus regarding tumors that measure 1-2 cm. In these cases, some histopathological features such as size, tumor grade, presence of lymphovascular invasion, or mesoappendix infiltration must also be considered. Computed tomography or magnetic resonance imaging scans are recommended for evaluating the presence of additional disease, except in the case of tumors smaller than 1 cm without additional risk factors. Somatostatin receptor scintigraphy or positron emission tomography with computed tomography should be considered in cases with suspected residual or distant disease. The main point of controversy is the indication for performing a completion right hemicolectomy after an initial appendectomy, based on the risk of lymph node metastases. The main factor considered is tumor size and 2 cm is the most common threshold for indicating a colectomy. Other factors such as mesoappendix infiltration, lymphovascular invasion, or tumor grade may also be considered. On the other hand, potential complications, and decreased quality of life after a hemicolectomy as well as the lack of evidence on benefits in terms of survival must be taken into consideration. In this review, we present data regarding the current indications, outcomes, and benefits of a colectomy.

Continuous renal replacement therapy versus intermittent hemodialysis as first modality for renal replacement therapy in severe acute kidney injury: a secondary analysis of AKIKI and IDEAL-ICU studies

BackgroundIntermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI.MethodsThis is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient’s modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting.ResultsA total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan–Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01–1·60). In a complementary analysis of less severely ill patients (SOFA score: 3–10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01–3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients.ConclusionCompared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique.

The addition of the immunomodulator mifamurtide to adjuvant chemotherapy for early osteosarcoma: a retrospective analysis.

Current treatment recommendations for high grade non-metastatic osteosarcoma include perioperative chemotherapy and surgery. Despite this intensive protocol, approximately 40% of patients will relapse. The addition of the immunomodulator mifamurtide to adjuvant cytotoxic chemotherapy was associated with a significant improvement in 6-year overall survival (OS) in young patients with resectable osteosarcoma, leading to its approval in Europe and other countries. Very limited real-world data are reported on its use. We retrospectively evaluated data from osteosarcoma patients who received mifamurtide in the adjuvant setting. Data were obtained from medical records in 2 high-volume bone sarcoma centers. The aim of this study was to collect real-world data on mifamurtide safety and efficacy in Greece. We identified 15 patients with completely resected osteosarcoma who received mifamurtide from September 2015 to January 2020. Median age at diagnosis was 24years old (16-76). Osteosarcoma arose in the lower extremities (n = 12), in the upper extremities (n = 2) or in the ilium (n = 1). The majority of patients (n = 13) received cisplatin/doxorubicin/methotrexate as perioperative chemotherapy and the remaining patients cisplatin/doxorubicin. After a median follow-up of 46.9months (range, 32.8-61.1), the median recurrence-free survival was 58.7months (range, 18.5-98.8) and the median OS 64.1months (range, 25.6-102.6). Except for fever and chills, the only adverse event probably related to mifamurtide was pericarditis (n = 1). Mifamurtide was well tolerated in a Greek osteosarcoma population, including patients older than 30years. The small sample size and the non-comparative design do not allow drawing conclusions on the drug benefit in terms of survival.

Emerging Drugs for Amyotrophic Lateral Sclerosis

&#x0D; Horizon scan reports provide brief summaries of information regarding new and emerging health technologies. These technologies are identified through the CADTH Horizon Scanning Service as topics of potential interest to health care decision-makers in Canada. This Horizon Scan summarizes the available information regarding emerging drug therapies for the treatment of patients with amyotrophic lateral sclerosis.&#x0D; Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disorder characterized by muscle weakness and wasting. ALS can be classified as sporadic (sALS), which accounts for 85% to 90% of the cases, or familial (fALS), which includes 10% to 15% of the cases.&#x0D; At present, 2 drugs are available in Canada for the treatment of patients with ALS, riluzole and edaravone. These 2 drugs provide modest benefits in terms of survival and function.&#x0D; Many treatments are currently in various stages of clinical development. Fasudil, ibudilast, inosine, and masitinib are drugs of interest as they have completed phase II, and some have initiated phase III, of their respective clinical development. Several other drugs are in clinical development and are briefly described in this report: AT-1501, CNM-Au8, Engensis, Pridopidine, Verdiperstat, and Zilucoplan.&#x0D; Emerging drugs for ALS pertain to different drug classes. Despite different mechanisms of action, these drugs all aim at providing a neuroprotective effect that will result in slowing of disease progression, maintenance of patient functional status, and improvement in patient survival.&#x0D; Of the 4 ALS drugs of interest in late-stage development, Fasudil, Ibudilast, and Inosine have completed phase II of clinical development.&#x0D; The estimated completion date for phase III of clinical development for Masitinib is December 2022.&#x0D;