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.     

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 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.     

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.     

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.     

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.     

Trends in surgery and survival for T1-T2 male breast cancer: A study from the National Cancer Database

BackgroundDespite evidence that early-stage male breast cancer (MBC) can be treated the same as in females, we hypothesized that men undergo more extensive surgery.MethodsPatients with clinical T1-2 breast cancer were identified in the National Cancer Database 2004–2016. Trends in surgery type and overall survival were compared between sexes.ResultsOf 9,782 males and 1,078,105 females, most were cN0 with AJCC stage I/II disease. Unilateral mastectomy was most common in men (67.1% vs. 24.1%, p < 0.001) and partial mastectomy in women (64.7% vs. 26.4%, p < 0.001), with no significant change over time. Over 1/3 of men received ALND in 2016. While overall survival was superior in females (HR 0.83, 95% CI 0.73–0.94, p = 0.003), partial mastectomy was associated with a 42% reduction in mortality risk for males (HR 0.58, 95% CI 0.4–0.8, p = 0.003).ConclusionsDe-escalation of surgery could be considered for MBC to improve survival and align with current standards of care.     

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.     

Epidemiological features of primary breast lymphoma patients and development of a nomogram to predict survival

BackgroundStudies on the epidemiology and prognosis of primary breast lymphoma (PBL) are lack for low incidence. Therefore, we aimed to investigate the epidemiological characteristics of PBL and develop nomograms to predict patient survival.MethodsData of patients who were diagnosed with PBL from 1975 to 2011 and incidence rate of PBL from 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Time-varying multivariable Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). Nomograms were constructed based on the independent prognostic factors identified in multivariate Cox regression analysis.ResultsA total of 1427 patients diagnosed with PBL were identified with the average age of 67.1 years. The overall incidence of PBL is 1.35/1,000,000 (adjusted to the United States standard population in 2000) from 1975 to 2017, with a significant upward trend by an annual percentage change (APC) of 2.91 (95%CI 2.29–3.94, P < 0.05). Age, sex, race, year of diagnosis, marital status, histological subtype, Ann Arbor Stage, and treatment modality were assessed as independent prognostic factors for OS and DSS by multivariable Cox regression (P < 0.05). Nomograms were constructed to predict the 1-, 3-, 5-, and 10- year OS and DSS. The concordance index (C-index) and calibration plots showed robustness and accuracy of the nomogram.ConclusionThe overall incidence of PBL was steadily increasing over the past four decades. Nomograms constructed can predicting 1-, 3-, 5-, and 10-year OS and identify patients with high-risk PBL.     

Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non–small cell lung cancer: A phase II study

IntroductionCurrently, limited data on tyrosine kinase inhibitors as neoadjuvant therapy exist. This prospective study aimed to investigate the efficacy and safety of preoperative gefitinib in patients with stage II-IIIA operable non–small cell lung cancer (NSCLC).MethodsThis was a single-arm, phase II trial performed in the Shanghai Cancer Center. Between August 2013 and October 2015, patients with operable stage II-IIIA NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation were enrolled. Patients were treated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints were the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival, and adverse events (AEs). ORR was defined as the proportion of patients achieving complete response or partial response radiologically. MPR was defined as no more than 10% viable tumor.ResultsOf the 35 eligible patients, 33 were considered as intention-to-treat population. ORR, the primary endpoint, was 54.5% (95% confidence interval [CI], 37.7-70.7), and the rate of MPR was 24.2% (95% CI, 11.9-40.4). Median DFS was 33.5 months (95% CI, 19.7-47.3); median overall survival was not reached. Skin toxicity (24/35,68.6%) and gastrointestinal symptoms (17/35,48.6%) were the most common AEs; no patients reported grade 3 or 4 AEs. After surgery, 4 patients experienced chylothorax (4/33,12.1%). Patients with MPR had a prolonged survival compared with those without (DFS, P = .019).ConclusionsNeoadjuvant therapy with gefitinib in patients with stage II-IIIA NSCLC is safe and may be a viable treatment for patients whose tumors have EGFR mutations. Patients with MPR were associated with improved survival.     

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.     

Safety and oncologic efficacy of percutaneous MRI-guided cryoablation of intraparenchymal renal cancers

PurposeThe purpose of this study was to evaluate the safety and oncologic efficacy of percutaneous magnetic resonance imaging (MRI)-guided cryoablation of intraparenchymal renal cancer.Materials and methodsBetween February 2009 and August 2019, 31 consecutives patients with 31 entirely intraparenchymal biopsy-proven renal cancers were treated with cryoablation under MRI-guidance in our institution, and were retrospectively included. There were 20 men and 11 women with a mean age of 68.5 ± 12.5 (SD) (range: 40–91 years). Patient, tumor- and procedure-related, and follow-up data were retrospectively collected and analyzed. Local recurrence free (LRFS), metastasis free (MFS), disease free (DFS), cancer specific (CSS), and overall survivals (OS) were calculated.ResultsPrimary and secondary technical efficacy rates were 94% and 100%, respectively. Median follow-up was 27 months. Seven (7/31; 23%) minor complications were noted in 7 patients. Patients showed a significant decline of the estimated glomerular filtration rate (eGFR) between baseline and nadir (mean basal eGFR 65.9 ± 22.4 [SD] mL/min/1.73 m² vs. mean nadir eGFR 52.8 ± 26.0 [SD] mL/min/1.73 m²; P < 0.001), but only two showed a clinically significant renal function decline. Three-year estimates of primary and secondary LRFS, MFS, and DFS were 64% (95% confidence interval [CI]: 47–87%), 89% (95% CI: 78–99%), 83% (95% CI: 77–98%), and 45% (95% CI: 28–73%), respectively. No patients died due to renal cancer evolution (three-year CSS of 100%; 95% CI: 100–100%). One patient died 52 months after the percutaneous treatment due to cryoablation-unrelated causes (three-year OS of 100%; 95% CI: 100–100%).ConclusionMRI-guided percutaneous cryoablation for intraparenchymal renal cancer offers good oncologic outcomes with acceptable complication rates and renal function worsening.     

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.     

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.     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.     

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.     

Aortic growth and development of partial false lumen thrombosis are associated with late adverse events in type B aortic dissection

BackgroundPatients with medically treated type B aortic dissection (TBAD) remain at significant risk for late adverse events (LAEs). We hypothesize that not only initial morphological features, but also their change over time at follow-up are associated with LAEs.Materials and MethodsBaseline and 188 follow-up computed tomography (CT) scans with a median follow-up time of 4 years (range, 10 days to 12.7 years) of 47 patients with acute uncomplicated TBAD were retrospectively reviewed. Morphological features (n = 8) were quantified at baseline and each follow-up. Medical records were reviewed for LAEs, which were defined according to current guidelines. To assess the effects of changes of morphological features over time, the linear mixed effects models were combined with Cox proportional hazards regression for the time-to-event outcome using a joint modeling approach.ResultsLAEs occurred in 21 of 47 patients at a median of 6.6 years (95% confidence interval [CI], 5.1-11.2 years). Among the 8 investigated morphological features, the following 3 features showed strong association with LAEs: increase in partial false lumen thrombosis area (hazard ratio [HR], 1.39; 95% CI, 1.18-1.66 per cm² increase; P < .001), increase of major aortic diameter (HR, 1.24; 95% CI, 1.13-1.37 per mm increase; P < .001), and increase in the circumferential extent of false lumen (HR, 1.05; 95% CI, 1.01-1.10 per degree increase; P < .001).ConclusionsIn medically treated TBAD, increases in aortic diameter, new or increased partial false lumen thrombosis area, and increases of circumferential extent of the false lumen are strongly associated with LAEs.     

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.     

Prognostic value of recurrence pattern in locally advanced esophageal squamous cell carcinoma: Results from the phase III trial NEOCRTEC5010

ObjectivesThe prognosis of patients with locally advanced esophageal squamous cell carcinoma with different recurrence backgrounds is highly heterogeneous. This study aims to explore the effects of recurrence patterns on prognosis.MethodsThe phase III, multicenter, prospective NEOCRTEC5010 trial enrolled 451 patients with stage IIB-III esophageal squamous cell carcinoma randomly assigned to neoadjuvant chemoradiotherapy combined with surgery (NCRT group) or surgery alone (S group) and followed them long-term. We investigated the effects of recurrence patterns on survival in patients undergoing radical esophagectomy.ResultsIn total, 353 patients were included in the study. The 5-year overall survival of patients with different recurrence patterns was significantly different: recurrence versus recurrence-free (17.8% vs 89.2%; P < .001), early recurrence versus late recurrence (4.6% vs 51.2%; P < .001), and distant metastasis versus locoregional recurrence (17.0% vs 20.0%; P = .666). Patients with early recurrence had significantly shorter survival after recurrence than those with late recurrence (hazard ratio, 1.541; 95% confidence interval, 1.047-2.268, P = .028). There was no significant difference in postrecurrence survival between patients with distant metastasis and locoregional recurrence (hazard ratio, 1.181; 95% confidence interval, 0.804-1.734; P = .396). Multivariate logistic analysis showed that pN1 stage, lymph node dissection <20, and lack of response to NCRT were independent risk factors for postoperative early recurrence. Multivariate Cox regression suggested that NCRT, age ≥60 years, early recurrence, and the pN1 stage were independent risk factors for shortened survival after recurrence.ConclusionsPrerecurrence primary tumor stage is inaccurate in predicting postrecurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is associated with a worse prognosis in patients with recurrence, especially early recurrence.     

Partial warfarin reversal prior to hip fracture surgical intervention in geriatric trauma patients effects on blood loss and transfusions

BackgroundWarfarin reversal is typically sought prior to surgery for geriatric hip fractures; however, patients often proceed to surgery with partial warfarin reversal. The effect of partial reversal (defined as having an international normalized ratio [INR] > 1.5) remains unclear.MethodsThis was a retrospective cohort study. Geriatric patients (≥65 y/o) admitted to six level I trauma centers from 01/2014-01/2018 with isolated hip fractures requiring surgery who were taking warfarin pre-injury were included. Warfarin reversal methods included: vitamin K, factor VIIa, (a)PCC, fresh frozen plasma (FFP), and the “wait and watch” method. An INR of ≤ 1.5 defined complete reversal. The primary outcome was the volume of blood loss during surgery; other outcomes included packed red blood cell (pRBC) and FFP transfusions, and time to surgery.ResultsThere were 135 patients, 44% partially reversed and 56% completely reversed. The median volume of blood loss was 100 mL for both those completely and partially reversed, p = 0.72. There was no difference in the proportion of patients with blood loss by study arm, 95% vs. 95%, p > 0.99. Twenty-five percent of those completely reversed and 39% of those partially reversed had pRBCs transfused, p = 0.08. Of those completely reversed 5% received an FFP transfusion compared to 14% of those partially reversed, p = 0.09. There were no statistically significant differences observed for the volume of pRBC or FFP transfused, or for time to surgery.ConclusionsPartial reversal may be safe for blood loss and blood product transfusions for geriatric patients with isolated hip fractures. Complete warfarin reversal may not be necessary prior to hip fracture surgery, especially for mildly elevated INRs.