Impact of body mass index on overall survival in patients with metastatic breast cancer

BackgroundHigh Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC).MethodsThe National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers.ResultsOf 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m² (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect.ConclusionOverweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.     

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis

ImportanceCarboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial.MethodsThe study was prospectively registered at PROSPERO (CRD42021228386).We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes.ResultsEight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I² 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I² 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44–3.08; I² 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm.Conclusionand relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.     

Prediction of overall survival in patients with hepatocellular carcinoma treated with Y-90 radioembolization by imaging response criteria

PurposeTo evaluate the potential of imaging criteria in predicting overall survival of patients with hepatocellular carcinoma (HCC) after a first transcatheter arterial yttrium-90 radioembolization (TARE)Materials and methodsFrom October 2013 to July 2017, 37 patients with HCC were retrospectively included. There were 34 men and 3 women with a mean age of 60.5 ± 10.2 (SD) years (range: 32.7–78.9 years). Twenty-five patients (68%) were Barcelona Clinic Liver Cancer (BCLC) C and 12 (32%) were BCLC B. Twenty-four primary index tumors (65%) were > 5 cm. Three radiologists evaluated tumor response on pre- and 4–7 months post-TARE magnetic resonance imaging or computed tomography examinations, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified RECIST (mRECIST), European Association for Study of the Liver (EASL), volumetric RECIST (vRECIST), quantitative EASL (qEASL) and the Liver Imaging Reporting and Data System treatment response algorithm. Kaplan–Meier survival curves were used to compare responders and non-responders for each criterion. Univariate and multivariate Cox proportional hazard ratio (HR) analysis were used to identify covariates associated with overall survival. Fleiss kappa test was used to assess interobserver agreement.ResultsAt multivariate analysis, RECIST 1.1 (HR: 0.26; 95% confidence interval [95% CI]: 0.09–0.75; P = 0.01), mRECIST (HR: 0.22; 95% CI: 0.08–0.59; P = 0.003), EASL (HR: 0.22; 95% CI: 0.07–0.63; P = 0.005), and qEASL (HR: 0.30; 95% CI: 0.12–0.80; P = 0.02) showed a significant difference in overall survival between responders and nonresponders. RECIST 1.1 had the highest interobserver reproducibility.ConclusionRECIST and mRECIST seem to be the best compromise between reproducibility and ability to predict overall survival in patients with HCC treated with TARE.     

A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

IntroductionPlatinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.Materials and methodsAll studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.ResultsFrom the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17–1.49, p < 0.00001; I² = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08–1.76, P = 0.009; I² = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48–2.47, p < 0.00001; I² = 32%), as well as PFS(HR 1.13, 95% CI 0.81–1.57, P = 0.47; I² = 0%) and OS (HR 1.89, 95% CI 1.22–2.92, P = 0.004; I² = 0%).ConclusionAccording to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.     

Local treatment options for young women with ductal carcinoma in situ: A systematic review and meta-analysis comparing breast conserving surgery with or without adjuvant radiotherapy,and mastectomy

PurposeYoung age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women.MethodsPubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest.ResultsWe included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50–0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98–1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06–9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes.ConclusionThis study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.     

Evaluation of efficacy and safety of PARP inhibitors in breast cancer: A systematic review and meta-analysis

BackgroundMany breast cancer clinical trials with PARPi have been completed or are currently carried out, either by monotherapy or combined with chemotherapy. We aim to assess the efficacy and safety of PARPi in breast cancer patients as compared to chemotherapy.MethodsA comprehensive literature search of PubMed, EMBASE, CENTRAL, conference meetings and clinical trial registry was performed. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR). The secondary outcome was safety profile. The comparative effects were measured using hazard ratio (HR) or relative risk (RR) with 95% confidence interval. Subgroup analyses were conducted based on types of intervention and baseline characteristics of patients.ResultsSix RCTs (n = 1953) were included. Two RCTs were recognized as high risk. PARPi was associated with an improved PFS (HR, 0.65; 95% CI, 0.56–0.74), OS (HR, 0.86; 95% CI, 0.73–1.01), and a higher ORR (RR, 1.38; 95% CI, 1.05–1.82). PARPi, however, significantly increased risk of grade 3–4 thrombocytopenia (RR, 1.63; 95% CI, 1.06–2.52). Monotherapy was observed with lower risk of disease progression and higher ORR rate than combination therapy, 0.56 to 0.65 and 2.21 to 1.05, respectively. For patients without prior platinum treatment, PARPi significantly improved PFS (HR, 0.64; 95% CI, 0.52–0.79).ConclusionsPARPi was observed with a significantly improved efficacy in aspects of PFS and ORR, but also higher risk of grade 3–4 thrombocytopenia as compared to chemotherapy. PARPi was a better choice for patients who had not received previous platinum treatment.     

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

BackgroundChemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.MethodsWe compared three different doses of q3w nab-PTX (Standard: 260 mg/m² [SD260] vs Medium: 220 mg/m² [MD220] vs Low: 180 mg/m² [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.ResultsOne hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.ConclusionsIntravenous administration of low-dose nab-PTX at 180 mg/m² q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.     

The impact of liver resection on survival for patients with metastatic breast cancer – A systematic review and meta-analysis

IntroductionThere is uncertainty surrounding the role of resection as an option for curative treatment of breast cancer with liver metastases (BCLM).AimTo perform a systematic review and meta-analysis evaluating the role of liver resection for BCLM.MethodsA systematic review was performed as per PRISMA guidelines. Hazard ratio (HR) for overall survival (OS) and standard error was obtained from each study and expressed using the generic inverse variance method, with a corresponding 95% confidence interval (CI). OS outcomes at 1- 3- and 5-years were expressed as dichotomous variables and pooled as odds ratios (OR) using the Mantel-Haenszel method.ResultsNine studies with 1732 patients were included. Of these, 24.5% underwent surgical resection of BCLM (424/1732) and 75.5% did not (1308/1732). Overall, OS was significantly better among those who underwent surgery versus controls (HR: 0.69, 95% CI: 0.59–0.80, P < 0.00001). Mortality rates were significantly reduced at 1-year (7.5% (10/134) vs 20.3% (79/390), OR: 0.25, 95% CI: 0.08–0.74, P = 0.010) and 5-years (54.0% (190/352) vs 75.3% (940/1249), OR: 0.46, 95% CI: 0.25–0.87, P = 0.020) respectively for those undergoing surgery versus controls. Mortality rates at 3 years after surgery were lower than the control group (19.1% (29/152) vs 53.0% (222/419)), however this failed to achieve statistical significance at meta-analysis (OR: 0.32, 95% CI: 0.09–1.12, P = 0.070).ConclusionLiver resection may be considered at multidisciplinary meetings for those with BCLM and offers a potentially curative option. However, judicious patient selection is crucial prior to making decisions in relation to resection of BCLM.     

Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

BackgroundThis meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR).MethodsA systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521).ResultsA total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50–4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95%CI, 1.93–6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67–4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03–14.1, P = 0.78).ConclusionsIncreased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.     

Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: A multi-institutional validation study

PurposeEmerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset.MethodsFifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control.ResultsIn total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26–1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56–415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84–46.70; p = 0.007) were independently associated with an increased risk of major complications.ConclusionA dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.     

Contemporary Epidemiology of and Risk Factors Associated with Removal of a Pathologically Normal Appendix in Children with Suspected Appendicitis

BackgroundThe goal of this study was to characterize contemporary performance benchmarks and risk factors associated with negative appendectomy (NA) in children with suspected appendicitis.MethodsA multicenter retrospective cohort analysis of children undergoing appendectomy for suspected appendicitis was performed using data from the 2016–2021 NSQIP-Pediatric Appendectomy Targeted Public Use Files. Multivariable regression was used to evaluate the influence of year, age, sex, and WBC count on NA rate, and to generate rate estimates for NA based on different combinations of demographic characteristics and WBC profiles.Results100,322 patients were included from 140 hospitals. The overall NA rate was 2.4%, and rates decreased significantly during the study period (2016: 3.1% vs. 2021: 2.3%, p < 0.001). In adjusted analyses, the highest risk for NA was associated with a normal WBC (<9000/mm³; OR 5.31 [95% CI: 4.87–5.80]), followed by female sex (OR 1.55 [95% CI: 1.42–1.68]) and age <5 years (OR 1.64 [95% CI 1.39, 1.94]). Model-estimated risk for NA varied significantly across demographic and WBC strata, with a 14.4-fold range in rates between subgroups with the lowest and highest predicted risk (males 13–17 years with elevated WBC [1.1%] vs. females 3–4 years with normal WBC [15.8%]).ConclusionsContemporary NA rates have decreased over time, however NA risk remains high in children without a leukocytosis, particularly for girls and children <5 years of age. These data provide contemporary performance benchmarks for NA in children with suspected appendicitis and identify high-risk populations where further efforts to mitigate NA risk should be targeted.Level of EvidenceIII.     

Influence of age as a continuous variable on the prognosis of patients with pT1-2N1 breast cancer

PurposeTo assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT).MethodsWe retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes.ResultsThe median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association <0.05; P-linear association >0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P < 0.05). In patients >50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS.ConclusionsAge was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.     

Infantile hypertrophic pyloric stenosis in Bosnia and Herzegovina: A retrospective cohort study from the largest tertiary care facility

BackgroundInfantile hypertrophic pyloric stenosis (IHPS) is the most common condition requiring surgery in infancy, but the etiology of IHPS is still unclear. The study aimed to analyze the epidemiological and clinical features of the infants with IHPS in our setting and determine the yearly trends in IHPS incidence in the Sarajevo Canton between 2007 and 2016.MethodsWe retrospectively analyzed epidemiologic, clinical, and operative data of all infants undergoing pyloromyotomy for IHPS over ten years in the largest tertiary care facility in Bosnia and Herzegovina.ResultsFifty-three IHPS patients were diagnosed, yielding an overall incidence of 1.17 per 1000 live births (1.25 and 1.09 cases in 2007–2011 and 2012–2016, respectively). IHPS was more prevalent among male infants (ratio 6.6:1, p < 0.001). The mean age at onset of symptoms was 39.6 days (range, 17–107 days). The estimated median time from symptoms onset to hospitalization was 11 days (range, 1–17 days). The mean age at diagnosis was significantly longer in premature infants compared with term infants (p = 0.003). Both first-born rank and bottle-feeding were significantly associated with IHPS (p = 0.001 and p = 0.04, respectively). No seasonal variation associated with IHPS was detected (p = 0.25). No evidence was found of differences in the incidence of IHPS related to maternal age (p = 0.24) and smoking (p = 0.59).ConclusionOur data indicate a declining trend and provide insights into the clinical characteristics of IHPS in Bosnia and Herzegovina. Most of the obtained results are in line with the published data and could improve the quality of local pediatric services.     

Validation of a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer

BackgroundTo date, it remains unclear which patients with breast cancer (BC) benefit from post-mastectomy radiotherapy (PMRT). Cheng et al. developed and validated a scoring system based on 4 prognostic factors for locoregional recurrence (LRR) to identify patients in need for PMRT. These factors include age, estrogen receptor status, lymphovascular status and number of affected axillary lymph nodes.PurposeTo validate the scoring system for LRR in BC developed by Cheng et al. by using an independent BC database.Methods and materialsWe retrospectively identified 1989 BC cases, treated with mastectomy (ME) with or without PMRT at the University Hospitals Leuven between 2000 and 2007. The primary endpoint was 5-year locoregional control rate with and without PMRT, according to the LRR score.ResultsMedian follow-up time was 11.4 years. After excluding patients with missing variables 1103 patients were classified using the LRR scoring system: 688 (62.38%) patients were at low risk of recurrence (LRR score 0–1), 335 (30.37%) patients were at intermediate risk of recurrence (LRR score 2–3) and 80 (7.25%) patients were at high risk of recurrence (LRR score ≥4). 5-year locoregional control rates with and without PMRT were 99.20% versus 99.21% (p = 0.43) in the low-risk group; 98.24% versus 85.74% (p < 0.0001) in the intermediate-risk group and 96.87% versus 85.71% (p = 0.10) in the high-risk group respectively.ConclusionOur validation of the LRR scoring system suggests it can be used to point out patients that would benefit from PMRT. We recommend further validation of this scoring system by other independent institutions before application in clinical practice.     

Effect of standard low-dose anthracycline chemotherapy on late congestive heart failure in breast cancer survivors aged between 50 and 59 at diagnosis: A nationwide study

ObjectivesAlthough chemotherapy-induced congestive heart failure (CHF) is a well-known adverse event in cancer survivors, the long-term risk of standard low-dose anthracycline has not yet been reported. This study aimed to investigate the long-term effects of standard anthracycline on late CHF in breast cancer survivors.Materials and methodsA nationwide retrospective cohort study was conducted using the national insurance claims data for nearly 98% of Korean citizens. Between Jan 2010 and Dec 2015, a total of 56,338 newly diagnosed female breast cancer survivors were included.ResultsThe total number of person-years was 199,648 and the incidence rate of late CHF was 3.57 per 1000 person-years. In multivariate analysis according to the subject’s age at diagnosis, only in the 50–59 age group, anthracycline-based [hazard ratio (HR) 1.765, 95% confidence interval (CI) 1.206–2.583] and taxane plus anthracycline-based regimens (HR 1.816, 95% CI 1.192–2.768) significantly increased the risk of late CHF. In the 50–59 age group, standard low-dose anthracycline significantly increased the risk of late CHF (HR 1.627, 95% CI 1.080–2.451) in Cox proportional hazard regression models. In competing risk model with recurrence and in-hospital death as competing risks, standard low-dose anthracycline was a significant risk factor for late CHF [subdistribution hazard ratio (SHR) 1.553, 95% CI 1.029–2.340].ConclusionThis nationwide study showed that standard chemotherapy with low-dose anthracycline is a risk factor for late-onset CHF in breast cancer survivors who were in their 50 s at breast cancer diagnosis. Long-term monitoring of late CHF should be considered in these younger breast cancer survivors.     

Higher-risk breast cancer in women aged 80 and older: Exploring the effect of treatment on survival

BackgroundTo understand the association between various treatments and survival for older women with higher-risk breast cancer when controlling for patient and tumor factors.Materials and methodsWe conducted a retrospective, population-based study. Women aged 80 years or older and diagnosed between 2004 and 2017 with non-metastatic, higher-risk breast cancer were identified form the provincial cancer registry in Alberta, Canada. Higher-risk was defined as any of following: T3/4, node positive, human epidermal factor receptor-2 (Her2) positive or triple negative disease. Treatments were surgery, radiotherapy and systemic therapy (hormonal therapy, and/or chemotherapy and/or trastuzumab) or a combination of the previous. Cox regression models were used to examine the association between treatments and breast cancer specific survival (BCSS) and overall survival (OS).Results1369 patients were included. The median age was 84 years. 332 (24%) of women had T3-T4 tumors, 792 (58%) had nodal involvement, 130 (10%) had Her2 positive tumors, 124 (9%) had triple negative tumors. After a median follow-up of 35 months, 29.5% of patients died of breast cancer whereas 34.2% died from other causes. Patients had a lower adjusted hazard for BCSS if they had surgery (hazard ratio [HR] = 0.37 95% confidence interval [CI]: 0.27, 0.51), or systemic therapy (HR = 0.75, 95%CI: 0.58, 0.98). Patients had an increased probability of breast cancer death in the first 5 years after diagnosis compared to death from other causes.ConclusionsSurgery and systemic therapy were associated with longer BCSS and OS. This suggests that maximizing treatments might benefit higher-risk patients.     

Clinical efficacy of direct or indirect left ventricular unloading during venoarterial extracorporeal membrane oxygenation for primary cardiogenic shock

ObjectiveLeft ventricular (LV) distention is a feared complication in patients receiving venoarterial (VA) extracorporeal membrane oxygenation (ECMO). LV unloading can be achieved indirectly with intra-aortic balloon pump (IABP) or directly with an Impella device (Abiomed, Danvers, Mass). We sought to assess the clinical and hemodynamic effects of IABP and Impella devices on patients supported with VA ECMO.MethodsWe conducted a retrospective review of VA ECMO patients at our institution from January 2015 to June 2020. Patients were categorized as either ECMO alone or ECMO with LV unloading. LV unloading was characterized as either ECMO with IABP or ECMO with Impella. We recorded baseline characteristics, survival, complications, and hemodynamic changes associated with device initiation.ResultsDuring the study, 143 patients received ECMO alone whereas 140 received ECMO with LV unloading (68 ECMO with IABP, 72 ECMO with Impella). ECMO with Impella patients had a higher incidence of bleeding events compared with ECMO alone or ECMO with IABP (52.8% vs 37.1% vs 17.7%; P < .0001). Compared with ECMO alone, ECMO with IABP patients had better survival at 180 days (log rank P = .005) whereas survival in ECMO with Impella patients was not different (log rank P = .66). In a multivariable Cox hazard analysis, age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.03; P = .015), male sex (HR, 0.54; 95% CI, 0.38-0.80; P = .002), baseline lactate (HR, 1.06; 95% CI, 1.02-1.11; P = .004), baseline creatinine (HR, 1.06; 95% CI, 1.00-1.11; P = .032), need for extracorporeal membrane oxygenation-cardiopulmonary resuscitation (HR, 2.09; 95% CI, 1.40-3.39; P = .001), and presence of pre-ECMO IABP (HR, 0.45; 95% CI, 0.25-0.83; P = .010) were associated with reduced mortality. There was no significant difference in hemodynamic changes in the ECMO with IABP versus ECMO with Impella cohorts.ConclusionsConcomitant support with IABP might help reduce morbidity and improve 180-day survival in patients receiving VA ECMO for cardiogenic shock.     

Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis

PurposeTo use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).Patients and methodsWe enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.ResultsAfter multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P < 0.0001) and 0.58 (0.47–0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2–4 (ypT3–4) and postchemotherapy pathologic nodal stages N2–3 (ypN2–3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38–0.69, P < 0.0001), 0.60 (0.40–0.88, P = 0.0096), and 0.64 (0.48–0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0–4, ypN0–3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.ConclusionFor patients with breast cancer ypT3–4, ypN2–3, or pathologic stages IIIA–IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.     

Biological versus mechanical prostheses for aortic valve replacement

ObjectivesLong-term real-world outcomes are critical for informing decisions about biological (Bio) or mechanical (Mech) prostheses for aortic valve replacement, particularly in patients aged between 50 and 65 years. The objective was to compare long-term survival and major adverse cardiac and cardiovascular events (ie, stroke, reoperation, and major bleeding) within this population.MethodsThis was a multicenter observational study including all patients aged between 50 and 65 years who underwent an aortic valve replacement because of severe isolated aortic stenosis between the years 2000 and 2018. A total of 5215 patients from 27 Spanish hospitals were registered with a follow-up of 15 years. Multivariable analyses, including a 2:1 propensity score matching (1822 Mech and 911 Bio) and competing risks analyses were applied.ResultsBio prostheses were implanted in 19% of patients (n = 992). No significant differences were observed between matched groups in long-term survival (hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.88-1.47; P = .33). Stroke rates were higher for Mech prostheses, but not significant (HR, 0.72; 95% CI, 0.50-1.03; P = .07). Finally, higher rates of major bleeding were found in the Mech group (HR, 0.65; 95% CI, 0.49-0.87; P = .004), whereas reoperation was more frequent among the Bio group (HR, 3.04; 95% CI, 1.80-5.14; P < .001). Bio prostheses increased from 13% in the period from 2000 to 2008 to 24% in 2009 to 2018.ConclusionsLong-term survival was comparable among groups in patients between 50 and 65 years of age. Mech prostheses were associated with a higher risk of major bleeding, whereas Bio prostheses entailed higher reoperation rates. Bio prostheses seem a reasonable choice for patients between 50 and 65 years in Spain.     

Proximal aortic repair in dialysis patients: A national database analysis

ObjectivesDialysis is a well-established risk factor for morbidity and mortality after cardiovascular procedures. However, little is known regarding the outcomes of proximal aortic surgery in this high-risk cohort.MethodsPerioperative (in-hospital or 30-day mortality) and 10-year outcomes were analyzed for all the patients who underwent open proximal aortic repair with the diagnosis of nonruptured thoracic aortic aneurysm (aneurysm, n = 325) or type A aortic dissection (dissection, n = 461) from 1987 to 2015 using the US Renal Data System database.ResultsIn patients with aneurysm, perioperative mortality was 12.6%. The 10-year mortality was 81% ± 3%. Age 65 years or more (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.03 to 1.78; P = .03), chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.01-2.82; P = .047), and Black race (HR, 1.46; 95% CI, 1.09-1.97; P = .01) were independently associated with worse 10-year mortality. In patients with dissection, perioperative mortality was 24.3% and 10-year mortality was 87.9% ± 2.2%. Age 65 years or more (HR, 1.49; 95% CI, 1.19-1.86; P < .001), congestive heart failure (HR, 1.39; 95% CI, 1.11-2.57; P = .004), and diabetes mellitus as the cause of dialysis (HR, 1.75; 95% CI, 1.2-2.57; P = .004) were independently associated with worse 10-year mortality. Black race (HR, 0.74; 95% CI, 0.6-0.92; P = .008) was associated with a better outcome.ConclusionsWe described challenging perioperative and 10-year outcomes for dialysis patients undergoing proximal aortic repair. The present study suggests the need for careful patient selection in the elective repair of proximal aortic aneurysm for dialysis-dependent patients, whereas it affirms the feasibility of emergency surgery for acute type A aortic dissections.