Summary
To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single cell analysis of the tumor, non-involved lung and blood cells together with multiplex tissue imaging to assess spatial cell distribution, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies.
(1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.
Patients who underwent pleurectomy/decortication had a better survival than those who underwent extrapleural pneumonectomy; however, the reasons are multifactorial and subject to selection bias. At present, the choice of resection should be tailored to the extent of disease, patient comorbidities, and type of multimodality therapy planned.
Purpose Neoadjuvant pemetrexed plus cisplatin was administered, followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation (RT), to assess the feasibility and efficacy of trimodality therapy in stage I to III malignant pleural mesothelioma. Patients and Methods Requirements included stage T1-3 N0-2 disease, no prior surgical resection, adequate organ function (including predicted postoperative forced expiratory volume in 1 second ≥ 35%), and performance status 0 to 1. Patients received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 for four cycles. Patients without disease progression underwent EPP followed by RT (54 Gy). The primary end point was pathologic complete response (pCR) rate. Results Seventy-seven patients received chemotherapy. All four cycles were administered to 83% of patients. The radiologic response rate was 32.5% (95% CI, 22.2 to 44.1). Fifty-seven patients proceeded to EPP, which was completed in 54 patients. Three pCRs were observed (5% of EPP). Forty of 44 patients completed irradiation. Median survival in the overall population was 16.8 months (95% CI, 13.6 to 23.2 months; censorship, 33.8%). Patients completing all therapy had a median survival of 29.1 months and a 2-year survival rate of 61.2%. Radiologic response of complete or partial response was associated with a median survival of 26.0 months compared with 13.9 months for patients with stable disease or progressive disease (P = .05). Conclusion This multicenter trial showed that trimodality therapy with neoadjuvant pemetrexed plus cisplatin is feasible with a reasonable long-term survival rate, particularly for patients who completed all therapy. Radiologic response to chemotherapy, but not sex, histology, disease stage, or nodal status, was associated with improved survival.
Introduction: Existing socioeconomic and racial disparities in healthcare access in New York City have likely impacted the public health response to COVID-19. An ecological study was performed to determine the spatial distribution of COVID-19 testing by ZIP code Tabulation Area and investigate if testing was associated with race or SES. Methods: Data were obtained from the New York City coronavirus data repository and 2018 American Community Survey 5-year estimates. A combined index of SES was created using principal component analysis and incorporated household income, gross rent, poverty, education, working class status, unemployment, and occupants per room. Multivariable Poisson regressions were performed to predict the number of total tests and the ratio of positive tests to total tests performed, using the SES index, racial composition, and Hispanic composition as predictors. Results: The number of total tests significantly increased with the increasing proportion of white residents (b=0.004, SE=0.001, p=0.0032) but not with increasing Hispanic composition or SES index score. The ratio of positive tests to total tests significantly decreased with the increasing proportion of white residents in the ZIP code Tabulation Area (b= À0.003, SE=0.000 6, p<0.001) and with increasing SES index score (b= À0.001 6, SE=0.0007, p=0.0159). Conclusions: In New York City, COVID-19 testing has not been proportional to need; existing socioeconomic and racial disparities in healthcare access have likely impacted public health response. There is urgent need for widespread testing and public health outreach for the most vulnerable communities in New York City.
VATS lobectomy and thoracotomy demonstrated similar 5-year survivals. However, VATS lobectomy was associated with fewer complications and shorter length of hospital stay.
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