Full author information is available at the end of the article Xuefeng Zang and Qian Wang contributed equally to this work. Hua Zhou, Sanhong Liu and Xinying Xue contributed equally to this work. The members of the COVID-19 Early Prone Position Study Group are listed in the Acknowledgements.

Anti-PD-1 treatment has shown unprecedented clinical success in the treatment of non-small-cell lung cancer (NSCLC), but the underlying mechanisms remain incompletely understood. Here, we performed temporal single-cell RNA and paired T-cell receptor sequencing on 47 tumor biopsies from 36 patients with NSCLC following PD-1-based therapies. We observed increased levels of precursor exhausted T (Texp) cells in responsive tumors after treatment, characterized by low expression of coinhibitory molecules and high expression of GZMK. By contrast, nonresponsive tumors failed to accumulate Texp cells. Our data suggested that Texp cells were unlikely to be derived from the reinvigoration of terminally exhausted cells; instead, they were accumulated by (1) local expansion and (2) replenishment by peripheral T cells with both new and pre-existing clonotypes, a phenomenon we named clonal revival. Our study provides insights into mechanisms underlying PD-1-based therapies, implicating clonal revival and expansion of Texp cells as steps to improve NSCLC treatment.

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ObjectivesTo investigate the characteristics and survival of lung cancer patients with additional malignant primary cancers.MethodsRecords of lung cancer patients newly diagnosed in Shanghai Pulmonary Hospital between January 2000 and January 2010 were retrospectively reviewed. Patients with second primary lung cancer and those with lung cancer only were included for detailed analysis.ResultsOf 27642 newly diagnosed lung cancer patients, 283 patients (1.02%) suffered previous additional primary cancers. Compared with single primary lung cancer, patients with secondary lung cancer associated other primary cancers were more often women (female to male ratio 1:1.72 vs 1:2.58, P = 0.018), older (64.2 vs 60.5 years old, P<0.001), more squamous cell type (30.7% vs 20.5%, P = 0.004), less small cell (3.9% vs 15.5%, P<0.001) type, at earlier stages (17.7% vs 11.0% for stage I, P = 0.014), and more frequently with family history of cancers (7.8% vs 3.9%, P = 0.038). The most common previous primary cancers observed were colorectal (22.0%), breast (18.4%), gastric (14.4%) and larynx cancers (11.9%). Approximately 42.9% of patients were diagnosed with lung cancer 2 to 6 years after diagnosis of initial primary cancers. The survival of patients with secondary lung cancer associated other malignancies was not significantly different from those with single lung cancer (P = 0.491), while synchronous multiple primary malignancies showed worse prognosis compared with those with metachronous ones or single lung cancer (p = 0.012).ConclusionThe possibility of second primary lung cancer should always be considered during the follow-up of related cancer types, especially those with family history of cancers. Patients with secondary lung cancer associated other primary malignancies have non-inferior survival than those with single lung cancer.

PurposeThis study aimed to establish a nomogram to predict the overall survival (OS) of the general non-small-cell lung cancer (NSCLC) patients with distant metastasis.Patients and methodsWe investigated Surveillance, Epidemiology, and End Results database for NSCLC patients with distant metastasis diagnosed between 2010 and 2014. Statistically significant prognostic factors were identified using uni- and multivariable Cox regression analyses. A nomogram incorporating these prognostic factors was developed and evaluated by the Harrell’s concordance index (C-index), calibration plots, and risk group stratifications.ResultsWe finally included 18,209 patients for analysis. These patients were divided into two groups, 14,567 cases for the training cohort and 3,642 for the validation cohort. Marital status, sex, race, age, histology, T stage, N stage, histological differentiation, bone metastasis, brain metastasis, liver metastasis, with M1a disease, surgery of primary cancer, and chemotherapy were identified as the prognostic factors of the OS and integrated to construct the nomogram. The nomogram had a C-index of 0.704 (95% CI: 0.699–0.709) in the training set and 0.699 (95% CI: 0.689–0.709) in the validation set. The calibration curves for 1- and 2-year OS in the training and validation sets showed acceptable agreement between the predicted and observed survival. Also, the nomogram was capable of stratifying patients into different risk groups within the patients who presented with bone, liver, or brain metastasis, as well as in each T, N stage, respectively.ConclusionA nomogram was established and validated to predict individual prognosis for the general patients with distantly metastatic NSCLC. Global prospective data with the latest TNM classification and more comprehensive prognostic factors are needed to improve this model.

PurposeMinimally invasive esophagectomy is increasingly performed for esophageal or gastroesophageal junctional cancer, with advantages of improved perioperative outcomes in comparison with open esophagectomy. McKeown and Ivor Lewis are widely used procedures of minimally invasive esophagectomy, and there have been controversies on which one is preferred for patients with resectable esophageal or junctional cancer.Patients and methodsThis review was registered at the International Prospective Register of Systematic Reviews (number CRD42017075989). Studies in PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were thoroughly investigated. Eligible studies included prospective and retrospective studies evaluating short-term outcomes of minimally invasive McKeown esophagectomy (MIME) vs minimally invasive Ivor Lewis esophagectomy (MILE) in patients with resectable esophageal or junctional tumors. Main parameters included anastomotic leak and 30-day/in-hospital mortality. Overall incidence rates (ORs)/weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated by employing random-effects models.ResultsFourteen studies containing 3,468 cases were included in this meta-analysis. Age, male sex, and American Joint Committee on Cancer (AJCC) stage between the 2 groups were not statistically different. MIME led to more blood loss, longer operating time, and longer hospital stay than MILE. MIME was associated with higher incidence of pulmonary complications (OR =1.96, 95% CI =1.28–3.00) as well as total anastomotic leak (OR =2.55, 95% CI =1.40–4.63), stricture (OR =2.07, 95% CI =1.05–4.07), and vocal cord injury/palsy (OR =5.62, 95% CI =3.46–9.14). In addition, the differences of R0 resection rate, number of lymph modes retrieved, blood transfusion rate, length of intensive care unit stay, incidence of cardiac arrhythmia, and Chyle leak between MIME and MILE were not statistically significant. Notably, incidence of severe anastomotic leak (OR =1.28, 95% CI =0.73–2.24) and 30-day/in-hospital mortality (OR =1.76, 95% CI =0.92–3.36) as well as 90-day mortality (OR =2.22, 95% CI =0.71–6.98) between the 2 procedures were also not significantly different.ConclusionThis study suggests that MIME and MILE are comparable with respect to clinical safety. MILE may be a better option when oncologically and clinically suitable. MIME is still a safe alternative procedure when clinically indicated. However, this evidence is at risk for bias; randomized controlled trials are needed to validate or correct our results.