NSCLC are seldom reported. Method: Consecutive patients with curative resected NSCLC and confirmed EGFR mutations at Fudan University Shanghai Cancer Center from January 2007 to December 2017, were retrospectively enrolled. The initial recurrence sites were recorded and categorized into five groups: thoracic recurrence, brain recurrence, neck recurrence, abdominal recurrence, and bone recurrence. The indicators of overall and site-specific recurrence were identified using the Cox regression model, where a panel of routinely used IHC markers (including Her2, Ki67, TTF-1, CK20, CK7, CK5/6, p53, RRM1, NapsinA, p40, syn, Bcl-2, CDX2, ERCC1 and p63) were incorporated. A nomogram was developed based on variables selected in multivariate analysis. The bootstrapping method (1000 repetitions) was applied to internally validate the nomogram Result: After a median follow-up of 32 (range, 5-122) months, disease recurrence was observed in 197(37.1%) out of the 531 patients, with a median recurrence-free survival (RFS) of 19 (95% CI, 16.63-21.37) months. Most patients (n¼136; 69.0%) had thoracic recurrence, followed by brain recurrence (n¼41; 20.8%), bone recurrence (n¼41; 20.8%), abdominal recurrence (n¼14; 7.1%), and neck recurrence (n¼13; 6.6%). Sex, tumor size, Ki67, and N stage were independent indicators of thoracic recurrence. Tumor size, N stage, CK20, and Syn were independent indicators of brain recurrence. N stage and Ki67 were independent indicators of bone recurrence. N stage was the independent indicator of abdominal recurrence and neck recurrence. Tumor size, Ki67, CK20, and N stage were independently associated with overall recurrence, and thus a nomogram predicting the 1-, 2-, and 3-year RFS probability was developed based on these four factors. The concordance index (C-index) was 0.723 (95% confidence interval, 0.675 to 0.771) and the calibration curves displayed good agreement between the predicted RFS and the actual observation.

BackgroundNeoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC) has improved pathological responses and survival rates compared with chemotherapy alone, leading to Food and Drug Administration (FDA) approval of nivolumab plus chemotherapy for resectable stage IB-IIIA NSCLC (AJCC 7th edition) without ALK or EGFR alterations. Unfortunately, a considerable percentage of tumors do not completely respond to therapy, which has been associated with early disease progression. So far, it is impossible to predict these events due to lack of knowledge. In this study, we characterized the gene expression profile of tumor samples to identify new biomarkers and mechanisms behind tumor responses to neoadjuvant chemoimmunotherapy and disease recurrence after surgery.MethodsTumor bulk RNA sequencing was performed in 16 pretreatment and 36 post-treatment tissue samples from 41 patients with resectable stage IIIA NSCLC treated with neoadjuvant chemoimmunotherapy from NADIM trial. A panel targeting 395 genes related to immunological processes was used. Tumors were classified as complete pathological response (CPR) and non-CPR, based on the total absence of viable tumor cells in tumor bed and lymph nodes tested at surgery. Differential-expressed genes between groups and pathway enrichment analysis were assessed using DESeq2 and gene set enrichment analysis. CIBERSORTx was used to estimate the proportions of immune cell subtypes.ResultsCPR tumors had a stronger pre-established immune infiltrate at baseline than non-CPR, characterized by higher levels of IFNG, GZMB, NKG7, and M1 macrophages, all with a significant area under the receiver operating characteristic curve (ROC) >0.9 for CPR prediction. A greater effect of neoadjuvant therapy was also seen in CPR tumors with a reduction of tumor markers and IFNγ signaling after treatment. Additionally, the higher expression of several genes, including AKT1, BST2, OAS3, or CD8B; or higher dendritic cells and neutrophils proportions in post-treatment non-CPR samples, were associated with relapse after surgery. Also, high pretreatment PD-L1 and tumor mutational burden levels influenced the post-treatment immune landscape with the downregulation of proliferation markers and type I interferon signaling molecules in surgery samples.ConclusionsOur results reinforce the differences between CPR and non-CPR responses, describing possible response and relapse immune mechanisms, opening the possibility of therapy personalization of immunotherapy-based regimens in the neoadjuvant setting of NSCLC.

Background: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients.Patients and methods: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial.

BackgroundLung cancer is currently the leading cause of cancer death. Despite its high incidence and mortality, there are few studies describing its symptoms at diagnosis broken down by tumour stage and tobacco use. Accordingly, this study was proposed to describe the frequency of the most common symptoms of non-small cell lung cancer and small cell lung cancer (SCLC) at diagnosis, with a breakdown by stage and tobacco use.Patients and methodsCases were collected from the Spanish Thoracic Tumour Registry, a nationwide registry sponsored by the Spanish Lung Cancer Group. More than 50 hospitals recruited histologically confirmed lung cancer cases and information was gathered through personal interview plus data contained in the electronic clinical record. There were no data available on the lag between the appearance of the first symptoms and diagnosis of lung cancer.ResultsA total of 9876 patients (74% male, median age 64 years) were recruited from 2016 to 2019. Of these, 12.5% presented with SCLC. Stage IV was the most frequent stage at diagnosis (46.6%), and the most frequent symptom was cough (33.9%), followed by dyspnoea (26.7%). No symptom was present in 59% of patients diagnosed in stage I; 40% of stage I patients presented with at least one symptom, while 27.7% of patients in stage IV had no symptoms at diagnosis. Cough was the most frequent symptom in SCLC (40.6%), followed by dyspnoea (34.3%). The number of symptoms was similar across the respective smoking categories in SCLC, and differences between the symptoms analysed did not exceed 7% in any case.ConclusionThe absence of the most frequent symptoms (ie, cough, pain, dyspnoea) should not lead to a decision to rule out the presence of lung cancer. A relevant percentage of stage IV patients displayed no symptoms at diagnosis.

Background: Lung cancer causes approximately 25% of all cancer deaths. Despite its relevance, few studies have analyzed differences by sex at the time of diagnosis in terms of symptoms, stage, age or smoking status.We aim to assess if there are differences between men and women on these characteristics at diagnosis. Methods:We analyzed the Thoracic Tumour Registry (TTR), sponsored by the Spanish Lung Cancer Group using a case-series design. This is a nationwide registry of lung cancer cases which started recruitment in 2016. For each case included, clinicians fulfilled an electronic record registering demographic data, symptoms, exposure to lung cancer risk factors, and treatment received in detail. We compared men and women using descriptive statistics.Results: A total of 13,590 participants took part in this study, 25.6% women. Women were 4 years younger than men (64 vs. 69), and men had smoked more frequently. Adenocarcinoma was the most frequent histological type in both sexes. Stage IV at diagnosis was 50.8% in women compared to 43.6% in men.Weight loss/anorexia/asthenia was the most frequent symptom in both sexes and there were no differences in the number of symptoms at diagnosis. There were no relevant differences in the frequency or number of symptoms by sex when non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) were analyzed separately. Smoking status did not appear to cause different lung cancer presentation in men compared to women. 2 Ruano-Ravina et al. Sex differences at lung cancer diagnosis