Survival In High-risk Patients Research Articles

Long term survival in high-risk patients after percutaneous mitral leaflet repair in a single centre: comparable mortality regardless of aetiology

Abstract Background Percutaneous mitral leaflet repair (PMVR) is a safe and effective alternative to conventional surgery in high-risk patients with both degenerative (DMR) and functional (FMR) mitral regurgitation. We present an analysis of a large cohort of consecutive patients treated with PMVR at a high-volume UK centre. Purpose We sought to analyse the outcomes of a group of patients undergoing PMVR over a 7-year period at a single centre, where surgery had been excluded. We hypothesised that the long-term mortality in this group would be high and would differ depending on the aetiology of MR. Methods We identified 246 consecutive patients over the duration of the PMVR programme, where follow up and pre-procedural data were available. We collected baseline characteristics including age at procedure, left ventricular ejection fraction (LVEF), left ventricular indexed diastolic volumes (LVEDVi) and aetiology of MR. Post procedural data included MR at end of procedure, all-cause mortality and duration of follow up. Results Baseline characteristics for the group, as a whole, were as follows: mean age 76±11 years, 170 (69%) male, DMR 136 (55%) vs. FMR 110 (45%), LVEF 49±15%. Baseline data by aetiology subgroup: mean age DMR 80±9 vs. FMR 71±11 (p<0.001), LVEF DMR 58±10 vs. FMR 40±14 (p<0.001), LVEDVi DMR 71±25 FMR 85±25 (p<0.001). 99% of patients were treated with the MitraClip® device (Abbott, US), 1% received the Pascal device (Edwards, US). Post-procedural MR grade was similar for both groups (DMR 1.5±0.8 vs. 1.4±0.8, p=NS). Overall procedural mortality was 0.4% and at a mean follow up of 1097 days (median 1021, IQR 289–1555) was 30.8%. Mortality was identical regardless of aetiology (DMR 30.9% vs. FMR 30.8%, p=NS). Conclusions This analysis of consecutive “real world” patients demonstrates encouraging survival outcome at a mean of 3 years after PMVR, regardless of MR aetiology. DMR patients tended to be older but with lower LVEDVi and significantly higher LVEF. These data compare favourably with the published literature, where mortality for mixed and similarly high-risk populations at 12 months averages approximately 20–25%. Mortality in our FMR group at 3 years was also similar to that seen in the recently published COAPT study at 2 years. We have demonstrated that PMVR is a safe option for our cohort of unselected high-risk patients presenting with either degenerative or functional MR. We hypothesise that the absence of survival difference could relate to the younger age of FMR patients despite the significantly lower baseline LVEF and higher ventricular volumes. This analysis encourages the more routine use of PMVR for FMR in the UK, where currently only DMR is commissioned. Funding Acknowledgement Type of funding source: None

Competing Endogenous RNA (ceRNA) Network Analysis of Autophagy-Related Genes in Hepatocellular Carcinoma.

PurposeAutophagy plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). We aimed to develop an autophagy-related genes signature predicting the prognosis of HCC and to depict a competing endogenous RNA (ceRNA) network.MethodsDifferentially expressed autophagy-related genes (DE-ATGs), miRNAs and lncRNAs and clinical data of HCC patients were extracted from TCGA. The GO and KEGG analysis were performed to investigate the gene function. Univariate and multivariate Cox regression analysis were used to identify a prognostic signature with the DE-ATGs. And a nomogram, adapted to the clinical characteristics, was established. Then, we established a ceRNA network related to autophagy genes.ResultsWe screened out 27 differentially expressed genes which were enriched in GO and KEGG pathways related to autophagy and cancers. In univariate and multivariate Cox regression analysis, BIRC5, HSPB8, and SQSTM1 were screened out to establish a prognostic risk score model (AUC=0.749, p<0.01). Kaplan–Meier survival analysis showed that the overall survival of high-risk patients was significantly worse. Furthermore, the signature was validated in the other two independent databases. The nomogram, including the autophagy-related risk signature, gender, stage and TNM, was constructed and validated (C-index=0.736). Finally, the ceRNA network was established based on DE-ATGs, differentially expressed miRNAs and lncRNAs.ConclusionWe constructed a reliable prognostic model of HCC with autophagy-related genes and depicted a ceRNA network of DE-ATGs in HCC which provides a basis for the study of post-transcriptional modification and regulation of autophagy-related genes in HCC.

Preoperative Predictors of Biochemical Recurrence-Free Survival in High-Risk Prostate Cancer Following Radical Prostatectomy.

Background: D'Amico high-risk prostate cancer (Pca) patients experience poor and heterogeneous oncological outcomes. This heterogeneity highlights a need to extensively explore factors associated with poor outcomes to guide decision-making.Objective: To assess predictors of biochemical recurrence (BCR)-free survival in high-risk patients following radical prostatectomy (RP), and subsequently establish a model predicting outcomes.Methods: We retrospectively identified D'Amico high-risk non-metastatic Pca patients who underwent RP between 2013 and 2019 in our hospital. We collected data including PSA level, clinical stage, biopsy Gleason score (GS), number of D'Amico high-risk factors (RF), the inflammatory status (Neutrophil-to-lymphocyte ratio [NLR], derived NLR [dNLR], platelet-to-lymphocyte ratio [PLR] and LDH). Kaplan–Meier methods were used to analyze BCR-free survival. Univariate and multivariate analyses were performed using Cox proportional hazards model to evaluate the association between clinicopathological parameters and BCR-free survival.Results: The median follow-up time for the 101 patients' cohort was 26 months (range: 3–81 months). The number of RF (1RF vs. ≥2RF), biopsy GS (<8 vs. ≥8), clinical stage (≤cT2c vs. >cT2c), pathological stage, and the presence of adverse pathological features were significant predictors of BCR (P < 0.05). Other parameters including inflammatory status (dNLR, NLR, PLR, and LDH) were not of predictive value. On multivariable analysis, biopsy GS (<8 vs. ≥8; HR 2.439) and clinical stage (≤cT2c vs. >cT2c; HR 3.271) were the independent predictors of BCR. Based on these two independent predictors, patients were stratified into three risk subgroups: favorable (0 risk factor; 47% of patients), intermediate (1 risk factor; 42 %), unfavorable (2 risk factors; 11%). The intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup (P < 0.001).Conclusion: Several factors are associated with BCR. Clinical stage (≤cT2c vs. >cT2c) and biopsy GS (<8 vs. ≥8) are the independent predictors of BCR. The stratification of high-risk patients into risk subgroups based on these two predictors shows that the intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup. The preoperative stratification model may help urologists and patients during decision-making. In non-metastatic high-risk patients, preoperative inflammatory markers (NLR, dNLR, PLR, and LDH) are not of prognostic value.

Role of radiation therapy in node-negative esophageal cancer: A propensity-matched analysis.

BackgroundThis study investigated the prognostic impact of (neo‐)adjuvant radiation therapies in early stage esophageal cancer.MethodsA retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database was conducted from 2004 to 2016. Patients with pathologically staged T1‐4N0M0 esophageal cancer were divided into two treatment groups: (i) neoadjuvant radiotherapy followed by surgery; and (ii) upfront esophagectomy followed by adjuvant radiotherapy. Propensity scored match and Cox proportional hazards model were used to identify covariates associated with overall survival and cancer‐specific survival.ResultsThere were 821 patients selected, of whom 588 (71.6%) received neoadjuvant radiotherapy and 233 (28.4%) received adjuvant radiotherapy. For the entire cohort, neoadjuvant radiotherapy was associated with a significantly benefit in five‐year survival outcomes compared with adjuvant radiotherapy (P < 0.01). After matching, the survival outcomes were still better for neoadjuvant radiotherapy than that of adjuvant treatment. Stratifying based on pathologic tumor status, neoadjuvant radiation was associated with improved CSS (five‐year survival 73.7% vs. 42.1%; P = 0.014) for localized (pT3‐4N0) disease. The Cox multivariate regression analysis revealed that the addition of neoadjuvant radiation for pT3‐4N0 diseases with tumor length ≥ 5 cm and squamous cell carcinoma, was a powerful prognostic factor for improved cancer‐specific survival (P < 0.01).ConclusionsCompared with adjuvant radiotherapy, the addition of neoadjuvant radiation for pT3‐4N0 diseases has been associated with improved cancer‐specific survival in high‐risk patients. Studies on preoperative neoadjuvant therapies would be plausible in high‐risk esophageal cancer patients.

Quest for Universal Health Coverage for Pediatric Acute Lymphoblastic Leukemia in Mexico

PURPOSE Until 2005, most Mexican children did not have coverage for cancer treatment. In that year, Seguro Popular began funding the treatment of children with acute lymphoblastic leukemia (ALL). We aimed to estimate 5-year survival in children with ALL. We also sought to evaluate the relationship of hospital volume, out-of-state treatment, and treatment administered by an adult hematologist to 5-year survival. METHODS We categorized patients according to risk (National Cancer Institute age criteria), hospital volume, out-of-state treatment, and treatment administered by an adult hematologist. We obtained overall 5-year survival using the Kaplan-Meier method and compared survival among groups. We used Cox proportional hazards regression analysis to conduct multivariable analysis and obtained hazard ratios (HRs) and 95% CI. RESULTS Between 2005 and 2015, 9,555 children were treated for ALL under Seguro Popular. Mean age (± standard deviation) was 7.4 (4.7) years. Five-year overall survival was 61% (95% CI, 60% to 62%); survival for high-risk patients was 51% (95% CI, 49% to 52%) and 66% (95% CI, 65% to 67%) for those with standard risk. We observed state heterogeneity (Sinaloa: 75% [95% CI, 69% to 80%] v Campeche: 45% [95% CI, 54% to 62%]). Patients who were treated in low-volume hospitals had lower survival rates compared with those treated in medium- and high-volume hospitals (HR v low, 1.17 [95% CI, 1.08 to 1.26]). Patients treated outside of their residence state had 10% lower mortality compared with those treated in their home state (HR, 0.89 [95% CI, 0.82 to 0.99]). The hazard of death among children who were treated by an adult hematologist was 1.93 times (95% CI, 1.44 times to 2.57 times) higher than the hazard of death among those treated by a pediatric oncologist/hematologist (26% [95% CI, 16% to 37%] v 61% [95% CI, 60% to 62%]). CONCLUSION Our results highlight the disparities in survival for ALL in Mexico. Health reform must consider increasing the patient volume required for hospital accreditation and mandating treatment by pediatric oncologists/hematologists.

Randomised clinical trial: standard of care versus early-transjugular intrahepatic porto-systemic shunt (TIPSS) in patients with cirrhosis and oesophageal variceal bleeding.

Early-transjugular intrahepatic porto-systemic shunt (TIPSS) has been recommended in international guidelines for high-risk patients with oesophageal variceal bleeding. To validate the results of a previous randomised control trial which supports use of early-TIPSS. In a two-centre open-label parallel-group randomised control trial, patients with cirrhosis and acute variceal bleeding were recruited following haemostasis with vaso-active drugs and endoscopic band ligation. Participants were randomised to standard of care or early-TIPSS. The primary outcome was 1-year survival, secondary outcomes included early and late rebleeding, and complications of portal hypertension. Fifty-eight patients (58±11.12years; 32.7% female) were randomised. After one year, seven patients died in the standard of care group and six in the early-TIPSS group, a 1-year survival of 75.9% vs 79.3% respectively (P=0.79). Variceal rebleeding occurred in eight patients in the standard of care group compared with three patients in the early-TIPSS group (P=0.09). Not all participants randomised to early-TIPSS received the intervention in time. For those receiving TIPSS per-protocol, variceal rebleeding rates were reduced (0% vs 27.6%, P=0.04) but this had no effect on survival (76.9% vs 75.9%, P=0.91). Serious adverse events were similar in both treatment groups, except that rates of hepatic encephalopathy were higher in patients receiving TIPSS (46.1% vs 20.7%, P<0.05). Early-TIPSS reduced variceal rebleeding, increased encephalopathy but had no effect on survival in high-risk patients with oesophageal variceal bleeding. Early-TIPSS may not be feasible in many centres however, larger studies are needed. ClinicalTrials.gov reference: NCT02377141.

Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells.

Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more tolerable and effective treatments for this disease. While the monoclonal antibody dinutuximab has demonstrated the potential for immunotherapy to improve overall NB outcomes, the 5-year overall survival of high-risk patients has not yet substantially changed. The frequency and type of invariant natural killer T cells (iNKTs) and natural killer cells (NKs) has been associated with improved outcomes in several solid and liquid malignancies, including NB. Indeed, iNKTs and NKs inhibit tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs), kill cancer stem cells (CSCs) and neuroblasts, and robustly secrete cytokines to recruit additional immune effectors. These capabilities, and promising pre-clinical and early clinical data suggest that iNKT- and NK-based therapies may hold promise as both stand-alone and combination treatments for NB. In this review we will summarize the biologic features of iNKTs and NKs that confer advantages for NB immunotherapy, discuss the barriers imposed by the NB tumor microenvironment, and examine the current state of such therapies in pre-clinical models and clinical trials.

A Randomized Controlled Trial of Bone–Patellar Tendon–Bone Anterior Cruciate Ligament Reconstruction With and Without Lateral Extra-articular Tenodesis: 19-Year Clinical and Radiological Follow-up

Background: Arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) with a bone–patellar tendon–bone graft (BTB) is a reliable surgical option for the control of anterior knee laxity after ACL injury. The addition of a lateral extra-articular tenodesis (LET) may improve control of rotation knee laxity and improve short-term graft survival in high-risk patients. Purpose: The aims of this study were to compare long-term patient-reported outcomes, graft survival, and risk of osteoarthritis between ACLR with and without LET. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: This study included 121 consecutive knees (120 patients) presenting to a single center with an ACL rupture between 1998 and 1999. In total, 61 knees were randomized to an isolated BTB ACLR, and 60 knees were randomized to a BTB ACLR with an extra-articular lateral tenodesis with gracilis tendon (modified Lemaire). Results: Eighty knees in 79 patients (66%) were available for follow-up at a postoperative mean of 19.4 years (range, 19-20.2). Of those patients, 43 had a clinical examination and completed patient-reported outcome questionnaires, and the other 37 patients were evaluated through the questionnaires alone. Standard radiographs were available for 45 patients and laximetry (TELOS) for 42 patients. Mean subjective International Knee Documentation Committee score at last follow-up was 81.8, and no differences were noted between the BTB and BTB-LET groups (P = .7). Two-thirds of patients were still participating in pivoting sports. A total of 17 knees (21%) experienced a graft failure, 5 of which (6%) underwent revision ACLR. There was no significant difference in graft failure risk between the BTB group (29%) and the BTB-LET group (13%; P = .1). Lateral tibiofemoral osteoarthritis was significantly more frequent in the BTB-LET group (59%) as compared with the BTB group (22%; P = .02). Lateral compartment osteoarthritis was correlated with partial lateral meniscectomy. Conclusion: There were no significant differences in long-term patient-reported outcomes after ACLR with or without an LET. LET may increase the risk of lateral compartment osteoarthritis at long-term follow-up. There was a trend toward decreased graft failure risk with the addition of LET but this study was underpowered to assess this outcome.

Less Invasive Approach to Left Ventricular Assist Device Implantation May Improve Survival in High-Risk Patients

Despite improvement in outcomes after left ventricular assist device (LVAD) implantation over the past 2 decades, high-risk recipients continue to have a prohibitive rate of morbidity and mortality. We hypothesized that a less invasive approach to LVAD implantation would be associated with improved survival compared to a conventional approach in this high-risk cohort. All consecutive LVAD recipients (2013 to 2017) that underwent centrifugal LVAD implantation were retrospectively reviewed. Patients were classified as high-risk if INTERMACS 1 or required temporary VAD/venoarterial extracorporeal membrane oxygenation prior to durable VAD implantation. Patients were stratified into 3 groups: left thoracotomy with hemi-sternotomy (LTHS) high-risk, conventional sternotomy (CS) high-risk, and non-high-risk. The primary outcome was 1-year survival. A total of 57 patients (LTHS high-risk: 11, CS high-risk: 12, non-high-risk: 34) were identified. Preoperative right ventricular failure scores, HeartMate-II mortality scores, and end-organ dysfunction were similar between the 2 high-risk groups. While operative time was similar between the 3 groups, cardiopulmonary bypass time was significantly shorter in the LTHS high-risk group compared to other groups. There was a trend toward decreased intensive care unit length of stay and ventilator time in LTHS high-risk compared to CS high-risk patients. Moreover, between these 2 groups, there was a significant decrease in temporary right VAD support (50% vs 0%, P = 0.014), and 1-year survival was significantly higher in the LTHS group (42% vs 91%, P = 0.025). Less invasive LVAD implantation appears to be associated with improved survival compared to conventional LVAD implantation in high-risk patients.

Integrating the Surprise Question, Palliative Care Screening Tool, and Clinical Risk Models to Identify Peritoneal Dialysis Patients With High One-Year Mortality

ContextUniversal screening to identify vulnerable patients who may receive limited benefits from life-sustaining treatments can facilitate palliative care in dialysis populations. ObjectivesWe aimed to develop prediction models for one-year mortality in peritoneal dialysis (PD) patients. MethodsThis prospective cohort study included 401 adult Taiwanese prevalent PD patients (average age 56.2 ± 14 years). In addition to obtaining clinical characteristics and laboratory data, the primary care nurses evaluated the surprise question (SQ) and palliative care screening tool (PCST) for each patient in March 2015. Multivariate logistic regression models were conducted to predict the primary outcome of one-year all-cause mortality. ResultsThere were 34 (8.5%) patients who died during the first year of follow-up. Patients allocated to the not surprised group according to the SQ and those who received a score of ≥4 on the PCST had increased odds of death (odds ratio 24.68 [95% CI 10.66–57.13] and 12.18 [95% CI 5.66–26.21], respectively). We also developed a clinical risk model for one-year mortality that included sex, dialysis vintage, coronary artery disease, malignancy, normalized protein nitrogen appearance, white blood cell count, and serum albumin and sodium levels. Integrating the SQ, PCST, and clinical risk model exhibited good discrimination with an area under the receiver operating characteristic curve of 0.95. Kaplan-Meier analysis showed worse survival in high-risk patients predicted by the integrated model (log-rank P < 0.001). ConclusionScreening with the use of the integrated measurement can identify high-risk PD patients. This approach may facilitate palliative care interventions for at-risk subpopulations.

Comparison of Overall Survival in High Risk Patients with Minimal Residual Disease after First-Line Treatment across Three Generations of Phase 3 Trials of the German CLL Study Group

Comparison of Overall Survival in High Risk Patients with Minimal Residual Disease after First-Line Treatment across Three Generations of Phase 3 Trials of the German CLL Study Group

Vaginal cuff brachytherapy in the adjuvant setting for patients with high-risk early-stage cervical cancer

PurposeTo evaluate local control and survival of high-risk patients with early-stage cervical cancer submitted or not to vaginal cuff brachytherapy in the postoperative setting. Methods and MaterialsIn this retrospective cohort of patients treated from 2010 to 2017, patients were eligible if they had confirmed histological diagnosis of cervical cancer treated with surgery and adjuvant radiotherapy with or without chemotherapy. Vaginal cuff brachytherapy (VCB) was indicated according to the radiation oncologist discretion. ResultsSeventy-nine patients were selected, with a median age at diagnosis of 47.5 years (26–77). Brachytherapy was delivered to 59 patients (74.7%). There were no significant differences between the VCB and the no-VCB groups. A total of 13 (16.5%) patients presented one or more events, 5 (25%) and 8 (13.5%) events in the no-VCB and VCB group, respectively. Most recurrences were pelvic and/or vaginal: 7/20 (35%) in the no-VCB group and 9/59 (10.2%) in the VCB group. There were eight systemic relapses with eight deaths. With a median followup of 45 months, mean overall survival and disease-free survival were, respectively, 85.1 and 83.8 months. No variables were correlated with overall survival. The only factor positively correlated to disease-free survival was VCB, with a mean of 86.9 and 68.4 months for patients who did and did not receive brachytherapy, respectively (p = 0.043). Vaginal recurrence was lower in the brachytherapy group, but with no statistical significance (p = 0.065). ConclusionVCB was associated with a reduced recurrence rate in the postoperative setting of high-risk patients with early-stage cervical cancer.

High impact of miRNA-4521 on FOXM1 expression in medulloblastoma

Medulloblastoma, an embryonal tumor of the cerebellum/fourth ventricle, is one of the most frequent malignant brain tumors in children. Although genetic variants are increasingly used in treatment stratification, survival of high-risk patients, characterized by leptomeningeal dissemination, TP53 mutation or MYC amplification, is still poor. FOXM1, a proliferation-specific oncogenic transcription factor, is deregulated in various solid tumors, including medulloblastoma, and triggers cellular proliferation, migration and genomic instability. In tissue samples obtained from medulloblastoma patients, the significant upregulation of FOXM1 was associated with a loss of its putative regulating microRNA, miR-4521. To understand the underlying mechanism, we investigated the effect of miR-4521 on the expression of the transcription factor FOXM1 in medulloblastoma cell lines. Transfection of this microRNA reduced proliferation and invasion of several medulloblastoma cell lines and induced programmed cell death through activation of caspase 3/7. Further, downstream targets of FOXM1 such as PLK1 and cyclin B1 were significantly reduced thus affecting the cell cycle progression in medulloblastoma cell lines. In conclusion, a restoration of miRNA-4521 may selectively suppress the pathophysiological effect of aberrant FOXM1 expression and serve as a targeted approach for medulloblastoma therapy.

Targeting PARP-1 with Alpha-Particles Is Potently Cytotoxic to Human Neuroblastoma in Preclinical Models.

Alpha-emitters can be pharmacologically delivered for irradiation of single cancer cells, but cellular lethality could be further enhanced by targeting alpha-emitters directly to the nucleus. PARP-1 is a druggable protein in the nucleus that is overexpressed in neuroblastoma compared with normal tissues and is associated with decreased survival in high-risk patients. To exploit this, we have functionalized a PARP inhibitor (PARPi) with an alpha-emitter astatine-211. This approach offers enhanced cytotoxicity from conventional PARPis by not requiring enzymatic inhibition of PARP-1 to elicit DNA damage; instead, the alpha-particle directly induces multiple double-strand DNA breaks across the particle track. Here, we explored the efficacy of [211At]MM4 in multiple cancers and found neuroblastoma to be highly sensitive in vitro and in vivo Furthermore, alpha-particles delivered to neuroblastoma show antitumor effects and durable responses in a neuroblastoma xenograft model, especially when administered in a fractionated regimen. This work provides the preclinical proof of concept for an alpha-emitting drug conjugate that directly targets cancer chromatin as a therapeutic approach for neuroblastoma and perhaps other cancers.

Comparative Effectiveness of Medical Therapy, Percutaneous Revascularization, and Surgical Coronary Revascularization in Cardiovascular Risk Subgroups of Patients With CKD: A Retrospective Cohort Study of Medicare Beneficiaries

Prior studies suggesting that medical therapy is inferior to percutaneous (percutaneous coronary intervention [PCI]) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization in chronic kidney disease (CKD) have not adequately considered medication optimization or baseline cardiovascular risk and have infrequently evaluated progression to kidney failure. We compared, separately, the risks for kidney failure and death after treatment with PCI, CABG, or optimized medical therapy for coronary disease among patients with CKD stratified by cardiovascular disease risk. Retrospective cohort study. 34,385 individuals with CKD identified from a national 20% Medicare sample who underwent angiography or diagnostic stress testing without (low risk) or with (medium risk) prior cardiovascular disease or who presented with acute coronary syndrome (high risk). PCI, CABG, or optimized medical therapy (defined by the addition of cardiovascular medications in the absence of coronary revascularization). Death, kidney failure, composite outcome of death or kidney failure. Adjusted relative rates of death, kidney failure, and the composite of death or kidney failure estimated from Cox proportional hazards models. Among low-risk patients, 960 underwent PCI, 391 underwent CABG, and 6,426 received medical therapy alone; among medium-risk patients, 1,812 underwent PCI, 512 underwent CABG, and 9,984 received medical therapy alone; and among high-risk patients, 4,608 underwent PCI, 1,330 underwent CABG, and 8,362 received medical therapy alone. Among low- and medium-risk patients, neither CABG (HRs of 1.22 [95% CI, 0.96-1.53] and 1.08 [95% CI, 0.91-1.29] for low- and medium-risk patients, respectively) nor PCI (HRs of 1.14 [95% CI, 0.98-1.33] and 1.02 [95% CI, 0.93-1.12], respectively) were associated with reduced mortality compared with medical therapy, but in low-risk patients, CABG was associated with a higher rate of the composite, death or kidney failure (HR, 1.25; 95% CI, 1.02-1.53). In high-risk patients, CABG and PCI were associated with lower mortality (HRs of 0.57 [95% CI, 0.51-0.63] and 0.70 [95% CI, 0.66-0.74], respectively). Also, in high-risk patients, CABG was associated with a higher rate of kidney failure (HR, 1.40; 95% CI, 1.16-1.69). Possible residual confounding; lack of data for coronary angiography or left ventricular ejection fraction; possible differences in decreased kidney function severity between therapy groups. Outcomes associated with cardiovascular therapies among patients with CKD differed by baseline cardiovascular risk. Coronary revascularization was not associated with improved survival in low-risk patients, but was associated with improved survival in high-risk patients despite a greater observed rate of kidney failure. These findings may inform clinical decision making in the care of patients with both CKD and cardiovascular disease.

Post-Operative Concurrent Chemoradiation for Patients with Non-Squamous Cell Carcinoma of Head and Neck: A Retrospective Cohort of the Uncommon Cancers

Background:Non-squamous cell carcinoma of the head and neck (HNnSCCA) is a rare tumor. Surgery is the standard treatment for resectable non-metastatic patients. Post-operative radiation (RT) is indicated for high-risk patients. No data from the randomized controlled trial utilizing post-operative concurrent chemoradiation (CCRT) is available. This study was aimed to determine the benefit of post-operative CCRT in the patients with resectable non-metastatic HNnSCCA. Methods:We retrospectively reviewed data of 139 patients with HNnSCCA (excluding nasopharyngeal, neuroendocrine, and skin cancers) who underwent surgery and post-operative radiation (RT) at Siriraj Hospital from 2009–2015. Results:Ninety-nine of the 139 patients had RT alone and 40 had CCRT. More patients receiving CCRT had ≥ one high-risk feature (80% CCRT vs. 57.6% RT; p=0.018). Five-year disease-free survival (DFS) and overall survival (OS) did not differ between the groups (58.6% CCRT vs. 68.2% RT; p=0.35 and 81.7% CCRT vs. 81.0% RT; p=0.35, respectively). Interestingly, post-operative CCRT was independently associated with significantly superior DFS (hazard ratio, HR 0.29; 95% confidence interval, CI 0.10 to 0.86; p=0.02) and OS (HR 0.08; 95% CI 0.01 to 0.43; p=0.003) according to multivariable analyses.Conclusion:Post-operative CCRT was associated with better survival in high-risk patients with resectable non-metastatic HNnSCCA comparing with post-operative RT alone. Post-operative CCRT might be considered as a treatment option for these patients.

Safety of nivolumab and ipilimumab in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).

6070 Background: Standard cisplatin-based chemoradiotherapy for LA SCCHN is associated with toxicity and less than desirable survival in high-risk patients (pts). The combination of the anti-PD1 antibody nivolumab (nivo) and the anti-CTLA-4 antibody ipilimumab (ipi) has been effective in melanoma and renal cell carcinoma and is under investigation in other solid tumors including SCCHN. Combining RT and immunotherapy (IO) has a strong preclinical rationale and is being evaluated in the clinic. This pilot trial combines IO and RT to build upon these observations. Methods: We enrolled previously untreated high-risk pts with AJCC 7th edition stage IVA-IVB SCCHN of the oral cavity, oropharynx (OP), hypopharynx, larynx. HPV+ OP tumors were T4, or N2c or N3 by AJCC 7th edition criteria. Nivo 3 mg/kg was administered every 2 weeks IV x 17 doses and ipi 1 mg/kg every 6 weeks x 6 doses beginning 2 weeks before IMRT 2 Gy/fraction/day given to total dose 70 Gy. The primary safety endpoint was acute in-field toxicity. Exploratory correlative studies include tumor PD-L1 expression, tumor immune bias, and exosome quantity and composition. The total sample size is 24 pts with 12 enrolled in the first stage and 12 in the expansion cohort. Results: A planned safety analysis was performed in the first 12 pts (8 OP; 1 hypopharynx; 3 larynx). No acute grade (G) 4 or dose-limiting toxicities were seen. Acute G 3 in-field toxicity occurred during RT in 50% of pts: dysphagia (4 pts), mucositis (3), odynophagia (2), hoarseness (1), dermatitis (1). 50% of pts had immune-related toxicity at any time. 3 pts discontinued treatment at &gt; 3 months post RT: 1 for an immune-related cause (G 3 colitis that resolved with steroids), and 2 for non-immune-related causes (1 G 5 bleeding due to carotid rupture secondary to an in-field ulcer at 4 months post RT in a pt with complete response and 1 G 3 OP ulcer resolving with hyperbaric oxygen). 1 pt with a laryngeal primary developed a solitary lung metastasis vs new primary 6 months post RT. 10 of 12 pts are alive with no evidence of disease (follow up 7.2-18.4 months). Conclusions: Preliminary results with this non-platinum-containing RT plus IO regimen are encouraging. Longer follow-up is needed for assessment of late effects and efficacy. Enrollment is ongoing in the expansion cohort. This study is supported by BMS. Clinical trial information: NCT03162731.

Improved outcomes from endovascular aortic repair in younger patients: Towards improved risk stratification.

ObjectivesAbdominal aortic aneurysms are conventionally treated by open repair surgery. While endovascular aortic repair improves survival in high-risk patients, younger patients (40–65 years) potentially at lower risk with asymptomatic abdominal aortic aneurysms undergoing endovascular aortic repair usually have poorer post-operative outcomes and require longer term follow-up. In this study, clinical data on younger patients were analyzed to investigate whether endovascular aortic repair leads to poorer short- and long-term outcomes.MethodsThis was a systematic review and meta-analysis of articles comparing clinical outcomes in patients aged 40–65 years undergoing open repair or endovascular aortic repair and published between 2000 and 2017. In-hospital mortality, long-term mortality, and post-operative complication data were retrieved from eligible studies and clinical outcomes were compared. Twenty-one retrospective cohort analyses were included, accounting for 250,837 patients (149,051 endovascular aortic repair; 101,786 open repair). Risk ratios were pooled using the DerSimonian and Laird random effects model. All statistical analyses were performed in Review Manager 5.3.ResultsYounger patients with asymptomatic abdominal aortic aneurysms undergoing endovascular aortic repair had a significantly reduced 30-day mortality (odds ratio (OR) = 0.40, 95% confidence intervals (CI) 0.28–0.57; p < 0.00001), long-term mortality (OR = 0.37, 95% CI 0.17–0.82; p = 0.01), incidence of reintervention (OR = 0.47, 95% CI 0.34–0.66; p < 0.0001), and incidence of renal failure (OR = 1.58, 95% CI 1.37–1.82; p < 0.00001).ConclusionsEndovascular aortic repair may improve short- and long-term survival and reduce post-operative complications in younger patients with asymptomatic abdominal aortic aneurysms.

The Impact of a Postmastectomy Chest Wall Scar Boost on Local Recurrence-free Survival in High-risk Patients

IntroductionA scar boost following postmastectomy radiation to a total dose of > 50 Gy can be considered in cases of invasive breast cancer with high-risk features including advanced tumor stage, lymphovascular space invasion (LVSI), and positive margins. The purpose of this study was to determine the impact of a scar boost on 5-year local recurrence-free survival (LRFS). Materials and MethodsWe retrospectively analyzed 140 patients with invasive breast cancer treated with mastectomy and postmastectomy radiation at a single institution between 2007 and 2016. Patients received 50 to 50.4 Gy to the chest wall and the majority of scar boosts were 9 to 10 Gy. LRFS was examined using the Kaplan-Meier method and univariable Cox regression. ResultsA total of 140 patients met inclusion criteria with a median follow-up time of 48 months. Ninety-four (67.1%) patients did receive a scar boost and 46 (32.9%) patients did not. On subset analysis of patients with LVSI or positive margins, 5-year LRFS was 79.3% in patients treated with scar boost compared with 71.1% in patients without a scar boost (P = .537). In patients with T3 or T4 disease, 5-year LRFS was 80.9% in those who received scar boost and 71.6% in patients who did not (P = .967). The use of a scar boost was not associated with a significant improvement in LRFS on Cox regression (hazard ratio, 0.83; 95% confidence interval, 0.37-1.84; P = .654). ConclusionUse of a scar boost following postmastectomy radiation decreased the absolute percentages of local recurrences in patients with high-risk features; however, this did not translate into a statistically significant benefit.

Bilateral Pulmonary Artery Banding before Norwood Procedure: Survival of High-Risk Patients

This study reports midterm results of high-risk patients with hypoplastic left ventricle treated with initial bilateral pulmonary artery banding (PAB) before secondary Norwood procedure (NP). Retrospective study of 17 patients admitted between July 2012 and February 2017 who underwent this treatment strategy because diagnosis or clinical status was associated with high risk for NP. Survival was compared with that of patients who underwent primary NP. Mean Aristotle comprehensive complexity score for NP would have been 19.7 ± 2.6. Risk factors included obstructed pulmonary venous return (n = 9), body weight < 2.5 kg (n = 7), total anomalous pulmonary venous connection (n = 3), and necrotizing enterocolitis (n = 1). Ten patients had a score ≥ 19.5. Early survival after PAB was 82.4% (14/17). NP was performed in 14 patients after improvement of clinical condition at a median age of 56 days and a weight ≥2,500 g. There was no 30-day mortality, but one interstage death. One patient died later after Glenn operation. One-year survival after primary PAB followed by NP was 70.6 ± 11.1%. During the same period, 35 patients with overall lower risk factors underwent primary NP; early postoperative survival and 1-year survival were 88.6 ± 5.4% and 68.6 ± 7.8%, respectively. There was no significant difference in survival between the two groups (p = 0.83) despite higher risk in the secondary Norwood group (p <0.0001). PAB before NP in high-risk patients constituted salvage management. Primary PAB provided enough time for stabilization and control of most risk factors. It allowed midterm survival equivalent to the survival after primary NP in lower risk neonates.