Sensitivity of Radial Endobronchial Ultrasound-Guided Bronchoscopy for Lung Cancer in Patients With Peripheral Pulmonary Lesions: An Updated Meta-analysis.

BACKGROUND: Registry trials have found radial endobronchial ultrasound (r-EBUS) sensitivity to vary between institutions, suggesting that in clinical practice, r-EBUS sensitivity may be lower than reported in clinical trials. We performed a meta-analysis to update the estimates of r-EBUS sensitivity and to explore factors contributing to heterogeneity of results. METHODS: A systematic review using PubMed was performed through July 2018 to determine the sensitivity of r-EBUS for lung cancer, and to construct a summary receiver operating characteristic curve. The DerSimonian and Laird method was used to weight results. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. Study quality was assessed using the QUADAS tool, and publication bias was tested using funnel plots. RESULTS: Fifty-one studies with a total of 7,601 patients were included. r-EBUS pooled sensitivity was 0.72 (95% CI, 0.70-0.75), and area under the sROC curve was 0.96 (95% CI, 0.94-0.97). Significant heterogeneity was observed (I2 = 76%; heterogeneity P < .01). We failed to demonstrate an association between sensitivity and air bronchus sign, average nodule size, use of fluoroscopy, virtual bronchoscopy, guide sheath, cancer prevalence, multicenter status, or consecutive enrollment. Rapid onsite cytology was associated with increased sensitivity (P = .01). The pooled pneumothorax rate was 0.7% (95% CI, 0.3%-1.1%). Funnel plots were asymmetrical, demonstrating sample size-related effects and possible publication bias. CONCLUSIONS: r-EBUS has an excellent safety profile, but there is significant between-study heterogeneity. Sample size-related effects and possibly publication bias have led to overly optimistic estimates of the sensitivity of r-EBUS.

Incidence, patterns of progression, and outcomes of preexisting and newly discovered brain metastases during treatment with anti-PD-1 in patients with metastatic melanoma.

BACKGROUND: Melanoma brain metastases (MBM) occur in up to 50% of patients with metastatic melanoma (MM) and represent a frequent site of systemic treatment failure for targeted therapies. However, to the authors' knowledge, little is known regarding the incidence, patterns of disease progression, and outcomes of MBM in patients treated with anti-PD-1 immunotherapy. METHODS: A total of 320 patients with MM who were treated with anti-PD-1 at The University of Texas MD Anderson Cancer Center in Houston were reviewed. Analyses were performed to identify factors associated with brain metastasis-free survival and overall survival (OS) using Cox regression models. RESULTS: The median age of the patients was 63.3 years. OS from the initiation of anti-PD-1 therapy was not significantly different between patients without MBM prior to anti-PD-1 compared with patients with prior MBM (P = .359). Among patients without prior MBM, 21 patients (8.6%) developed MBM during anti-PD-1 therapy, 12 of whom (4.9%) presented with disease progression in the central nervous system (CNS) only. Developing MBM during or after therapy with anti-PD-1 (hazard ratio, 4.70; 95% CI, 3.18-6.93) was associated with shorter OS. Among patients with MBM prior to anti-PD-1 treatment, 15 (20.0%) progressed in the CNS only and 19 (25.3%) progressed both intracranially and extracranially; at the time of the last data cutoff, 27 patients (36.0%) had not developed disease progression. Radiation necrosis occurred in 11.3% of patients (7 of 62 patients) in the group with a prior MBM who received stereotactic radiosurgery. CONCLUSIONS: Anti-PD-1 therapy may change the natural history of patients with preexisting MBM. However, CNS failure during treatment with anti-PD-1 is predictive of a worse prognosis compared with extracranial progression. The results of the current study support the activity of anti-PD-1 in patients with MBM, although routine CNS imaging during therapy is warranted.

The pattern of myometrial invasion as a predictor of lymph node metastasis or extrauterine disease in low-grade endometrial carcinoma.

The purpose of this study was to examine predictors of lymph node (LN) metastases or extrauterine disease (ED) in low-grade (FIGO grade 1 or 2) endometrioid carcinoma (LGEC) in a multi-institutional setting. For LGEC with and without LN metastasis or ED, each of the 9 participating institutions evaluated patients' age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic, elongated, and fragmented glands (MELF), single-cell/cell-cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement, and numbers of pelvic and para-aortic LNs sampled. A total of 304 cases were reviewed: LN(+) or ED(+), 96; LN(-)/ED(-), 208. Patients' ages ranged from 23 to 91 years (median 61 y). Table 1 summarizes the histopathologic variables that were noted for the LN(+) or ED(+) group: tumor size ≥2 cm, 93/96 (97%); MI>50%, 54/96 (56%); MELF, 67/96 (70%); SCI, 33/96 (34%); LVI, 79/96 (82%); >20% solid, 65/96 (68%); papillary architecture present, 68/96 (72%); LUS involved, 64/96 (67%); and CX involved, 41/96 (43%). For the LN(-)/ED(-) group, the results were as follows: tumor size ≥2 cm, 152/208 (73%); MI>50%, 56/208 (27%); MELF, 79/208 (38%); SCI, 19/208 (9%); LVI, 56/208 (27%); >20% solid, 160/208 (77%); papillary architecture present, 122/208 (59%); LUS involved, 77/208 (37%); CX involved, 24/208 (12%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (P=0.9 and 0.1, respectively). After multivariate analysis, the depth of MI, CX involvement, LVI, and SCI emerged as significant predictors of advanced-stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced-stage disease, these were not shown to be significant by multivariate analysis. This study validates MI, CX involvement, and LVI as significant predictors of LN(+) or ED(+). The association of SCI pattern with advanced-stage LGEC is a novel finding.

Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant.

Unrelated cord blood transplant (CBT) is an alternative treatment option for patients who lack a matched donor. However, the optimal type and intensity of the preparative regimen remains unclear. We evaluated the toxicity and outcomes of a conditioning regimen consisting of melphalan 140 mg/m(2) (day - 8), thiotepa 10 mg/kg (day - 7), fludarabine 160 mg/m(2) over 4 days (days - 6 to - 3) and rabbit antithymocyte globulin (ATG) 1.25 mg/kg (day - 4) and 1.75 mg/kg (day - 3) (FMT). Forty-seven patients with advanced hematologic malignancies with a median age of 23 years (30 adults and 17 children) were treated. Sixty percent of patients were in remission at transplant. Ninety-one percent of the patients engrafted neutrophils after a median of 22 days, and all but one of the patients achieving donor engraftment had hematopoietic recovery with 100% cord blood-derived cells. Grade 3 gastrointestinal toxicity was the major non-hematopoietic toxicity, occurring in 32% of patients. Cumulative incidence of day-100 grade II-IV acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) was 53% and 34%, respectively, and non-relapse mortality at day 100 and 2 years was 11% and 40%. Two-year disease-free and overall survival rates were 31% and 44%, respectively. These results suggest that FMT is a feasible conditioning regimen for patients undergoing CBT.