Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in ER+/HER2- breast cancer pts with 1-3 positive nodes and oncotype DX recurrence score 20 to 25: an NCDB analysis

BackgroundThe RxPONDER trial found that among breast cancer patients with estrogen receptor positive (ER+) breast cancer, 1-3 positive axillary nodes, and a recurrence score of ≤25, only pre-menopausal women benefitted from adjuvant chemoendocrine therapy; postmenopausal women with similar characteristic did not benefit from adjuvant chemotherapy. We aimed to replicate the RxPonder trial using a larger patient cohort with real world data to determine whether a RS threshold existed where adjuvant chemotherapy was beneficial regardless of age.MethodsThe National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS ≤25 who received endocrine (ET) only or chemo-endocrine therapy (CET). Cox regression interaction was explored between CET and age as a surrogate for menopausal status.ResultsThe final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS >20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age <=50: HR = 0.334, P=0.002; age>50: HR=0.521, P=0.019).ConclusionAmong women with ER+/HER2- breast cancer with 1–3 positive nodes, and a RS of 20-25—in contrast to the RxPONDER trial—we observed that CET was associated with an OS benefit in women regardless of age

Fiducial marker placement with electromagnetic navigation bronchoscopy: a subgroup analysis of the prospective, multicenter NAVIGATE study

Fiducial markers (FMs) help direct stereotactic body radiation therapy (SBRT) and localization for surgical resection in lung cancer management. We report the safety, accuracy, and practice patterns of FM placement utilizing electromagnetic navigation bronchoscopy (ENB). Methods: NAVIGATE is a global, prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system. This prospectively collected subgroup analysis presents the patient demographics, procedural characteristics, and 1-month outcomes in patients undergoing ENB-guided FM placement. Follow up through 24 months is ongoing. Results: Two-hundred fifty-eight patients from 21 centers in the United States were included. General anesthesia was used in 68.2%. Lesion location was confirmed by radial endobronchial ultrasound in 34.5% of procedures. The median ENB procedure time was 31.0 min. Concurrent lung lesion biopsy was conducted in 82.6% (213/258) of patients. A mean of 2.2 ± 1.7 FMs (median 1.0 FMs) were placed per patient and 99.2% were accurately positioned based on subjective operator assessment. Follow-up imaging showed that 94.1% (239/254) of markers remained in place. The procedure-related pneumothorax rate was 5.4% (14/258) overall and 3.1% (8/258) grade ⩾ 2 based on the Common Terminology Criteria for Adverse Events scale. The procedure-related grade ⩾ 4 respiratory failure rate was 1.6% (4/258). There were no bronchopulmonary hemorrhages. Conclusion: ENB is an accurate and versatile tool to place FMs for SBRT and localization for surgical resection with low complication rates. The ability to perform a biopsy safely in the same procedure can also increase efficiency. The impact of practice pattern variations on therapeutic effectiveness requires further study

Motor Vehicle Protective Device Usage Associated with Decreased Rate of Flail Chest: A Retrospective Database Analysis

Background and Objectives: Protective equipment, including seatbelts and airbags, have dramatically reduced the morbidity and mortality rates associated with motor vehicle collisions (MVCs). While generally associated with a reduced rate of injury, the effect of motor vehicle protective equipment on patterns of chest wall trauma is unknown. We hypothesized that protective equipment would affect the rate of flail chest after an MVC. Materials and Methods: This study was a retrospective analysis of the 2019 iteration of the American College of Surgeons Trauma Quality Program (ACS-TQIP) database. Rib fracture types were categorized as non-flail chest rib fractures and flail chest using ICD-10 diagnosis coding. The primary outcome was the occurrence of flail chests after motor vehicle collisions. The protective equipment evaluated were seatbelts and airbags. We performed bivariate and multivariate logistic regression to determine the association of flail chest with the utilization of vehicle protective equipment. Results: We identified 25,101 patients with rib fractures after motor vehicle collisions. In bivariate analysis, the severity of the rib fractures was associated with seatbelt type, airbag status, smoking history, and history of cerebrovascular accident (CVA). In multivariate analysis, seatbelt use and airbag deployment (OR 0.76 CI 0.65–0.89) were independently associated with a decreased rate of flail chest. In an interaction analysis, flail chest was only reduced when a lap belt was used in combination with the deployed airbag (OR 0.59 CI 0.43–0.80) when a shoulder belt was used without airbag deployment (0.69 CI 0.49–0.97), or when a shoulder belt was used with airbag deployment (0.57 CI 0.46–0.70). Conclusions: Although motor vehicle protective equipment is associated with a decreased rate of flail chest after a motor vehicle collision, the benefit is only observed when lap belts and airbags are used simultaneously or when a shoulder belt is used. These data highlight the importance of occupant seatbelt compliance and suggest the effect of motor vehicle restraint systems in reducing severe chest wall injuries

Desaturation during Six-Minute Walk Testing Predicts Major Morbidity Following Anatomic Lung Resection among Patients with COPD

Background: Pulmonary function testing (PFT) is commonly used to risk-stratify patients prior to lung resection. Guidelines recommend that patients with reduced lung function, due to chronic lung conditions such as Chronic Obstructive Pulmonary Disease (COPD), should receive additional physiologic testing to determine fitness for resection. We reviewed our experience with six-minute walk testing (SMWT) to determine the association of test results and post-operative complications. Methods: Consecutive adult patients undergoing segmentectomy, lobectomy, bilobectomy or pneumonectomy between 1 January, 2007 and 1 January, 2017 were identified in a prospectively maintained database. Patients with poor lung function, as defined by percent predicted forced expiratory volume in 1 s (FEV1) or diffusion capacity of carbon monoxide (DLCO) ≤60%, had results of SMWT extracted from their chart. Association of test result to post-operative events was performed. Results: 581 patients had anatomic lung resections with predicted post-operative FEV1 or DLCO values ≤60%, consistent with a diagnosis of COPD. Among them, 50 (8.6%) had preoperative SMWT performed. Patients who received SMWT were more likely to have a FEV1 or DLCO less than 40 percent predicted (24/50 (48.0%) vs 166/531 (31.3%), p = 0.016). Post-operatively, patients who had SMWT performed had higher rates of pneumonia, but similar rates of major morbidity. The post-exercise oxygen saturation and the amount of desaturation correlated with the occurrence of major morbidity. In multivariable regression, oxygen desaturation was an independent risk factor for the occurrence of major morbidity, and desaturation was an excellent predictor of major morbidity by receiver operating characteristic curves analsysis. Conclusions: Among patients with elevated risk, oxygen desaturation during SMWT was independently associated with the occurence of major morbidity in multivariable analysis, while pulmonary function testing was not. SMWT is an important tool for risk-stratification, and may be underutilized

Frailty is associated with 90-day mortality in urgent thoracic surgery conditionsCentral MessagePerspective

Objective: In patients undergoing elective thoracic surgery, frailty is associated with worse outcomes. However, the magnitude by which frailty influences outcomes of urgent thoracic surgery (UTS) is unknown. Methods: We identified patients admitted with a UTS condition from January to September 2017 in the National Readmissions Database. UTS conditions were classified as esophageal perforation, hemo/pneumothorax, rib fracture, and obstructed hiatal hernia. Outcome of interest was mortality within 90 days of index admission. Frailty score was calculated using a deficit accumulation method. Cox proportional hazard modeling was used to calculate a hazard ratio for each combination of UTS disease type and frailty score, adjusted for sex, insurance payor, hospital size, and hospital and patient location, and was compared with the effect of frailty on elective lung lobectomy. Results: We identified 107,487 patients with a UTS condition. Among UTS conditions overall, increasing frailty elements were associated with increased mortality (hazard ratio, 2270; 95% CI, 1463-3523; P < .001). Compared with patients without frailty undergoing elective lobectomy, increasing frailty demonstrated trending toward increased mortality in all diagnoses. The magnitude of the effect of frailty on 90-day mortality differed depending on the disease and level of frailty. Conclusions: The effect of frailty on 90-day mortality after admission for urgent thoracic surgery conditions varies by disease type and level of frailty. Among UTS disease types, increasing frailty was associated with a higher 90-day risk of mortality. These findings suggest a valuable role for frailty evaluation in both clinical settings and administrative data for risk assessment

SCCRO Promotes Glioma Formation and Malignant Progression in Mice1

Originally identified as an oncogene activated by amplification in squamous cell carcinomas, several lines of evidence now suggest that squamous cell carcinoma-related oncogene (SCCRO; aka DCUN1D1) may play a role in the pathogenesis of a wide range of human cancers including gliomas. SCCRO's oncogenic function is substantiated by its ectopic expression, resulting in transformation of cells in culture and xenograft formation in nude mice. The aim of this study was to assess the in vivo oncogenicity of SCCRO in a murine model. Ubiquitous expression of SCCRO resulted in early embryonic lethality. Because SCCRO overexpression was detected in human gliomas, its in vivo oncogenic activity was assessed in an established murine glioma model. Conditional expression of SCCRO using a replication-competent ASLV long terminal repeat with splice acceptor/nestin-(tumor virus-A) tv-a model system was not sufficient to induce tumor formation in a wild-type genetic background, but tumors formed with increasing frequency and decreasing latency in facilitated background containing Ink4a deletion alone or in combination with PTEN loss. Ectopic expression of SCCRO in glial progenitor cells resulted in lower-grade gliomas in Ink4a-/- mice, whereas its expression in Ink4a-/-/PTEN-/- background produced high-grade glioblastoma-like lesions that were indistinguishable from human tumors. Expression of SCCRO with platelet-derived growth factor-beta (PDGF-β) resulted in an increased proportion of mice forming glioblastoma-like tumors compared with those induced by PDGF-β alone. This work substantiates SCCRO's function as an oncogene by showing its ability to facilitate malignant transformation and carcinogenic progression in vivo and supports a role for SCCRO in the pathogenesis of gliomas and other human cancers