eComment. Does resected lymph-node number influence survival in non-small cell lung cancer?

n/

Does Myasthenia Gravis Affect Long-Term Survival in Thymic Carcinomas? An ESTS Database Analysis

Background: Thymic carcinoma is a rare and highly malignant tumor with a dismal prognosis, which occasionally coexists with myasthenia gravis (MG). This study aims to investigate the MG incidence on a surgical cohort of patients with thymic carcinoma and to explore its influence on long-term survival. Methods: the prospectively collected data from the ESTS database on thymic epithelial tumors were reviewed. Clinical, pathological, and survival information on thymic carcinoma were analyzed. Results: the analysis was conducted on 203 patients, with an equal gender distribution (96 males and 107 females). MG was detected in 22 (10.8%) patients, more frequently elderly (>60 years, p = 0.048) and male (p = 0.003). Induction therapy was performed in 22 (10.8%) cases. After surgery, 120 (59.1%) patients had a Masaoka stage II-III while complete resection (R0) was achieved in 158 (77.8%). Adjuvant therapy was performed in 68 cases. Mean follow-up was 60 (SD = 14) months. The 3-year, 5-year and 10-year survival rates were 79%, 75% and 63%, respectively. MG did not seem to influence long-term survival (5-year survival in non-MG-TCs 78% vs. 50% in MG-TCs, p = ns) as age < 60 years, female gender, early Masaoka stage, and postoperative radiotherapy did, conversely. Conclusions: myasthenia occurred in about 10% of thymic carcinomas and it did not seem to affect significantly the long-term prognosis in surgically treated thymic carcinoma-patients

BET inhibitors drive Natural Killer activation in non-small cell lung cancer via BRD4 and SMAD3

Non-small-cell lung carcinoma (NSCLC) is the most common lung cancer and one of the pioneer tumors in which immunotherapy has radically changed patients’ outcomes. However, several issues are emerging and their implementation is required to optimize immunotherapy-based protocols. In this work, we investigate the ability of the Bromodomain and Extra-Terminal protein inhibitors (BETi) to stimulate a proficient anti-tumor immune response toward NSCLC. By using in vitro, ex-vivo, and in vivo models, we demonstrate that these epigenetic drugs specifically enhance Natural Killer (NK) cell cytotoxicity. BETi down-regulate a large set of NK inhibitory receptors, including several immune checkpoints (ICs), that are direct targets of the transcriptional cooperation between the BET protein BRD4 and the transcription factor SMAD3. Overall, BETi orchestrate an epigenetic reprogramming that leads to increased recognition of tumor cells and the killing ability of NK cells. Our results unveil the opportunity to exploit and repurpose these drugs in combination with immunotherapy

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study)

Background Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58–85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P&lt;0.0001); incidental diagnosis of lung cancer (HR: 1.71; P&lt;0.0001); and lung cancer resection (HR: 2.79; P&lt;0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P&lt;0.0001); incidental diagnosis of lung cancer (HR: 2.00; P&lt;0.0001); and lung cancer resection (HR: 2.07; P&lt;0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). Conclusions The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival

Impact of High‑Grade Patterns in Early‑Stage Lung Adenocarcinoma: A Multicentric Analysis

Objective The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a signifcantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. Methods We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Diferences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-highgrade and high-grade patterns. Results Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a signifcant better prognosis compared to T1a-b-c with high-grade pattern (p=0.020), but the latter had similar OS compared to T2a (p=0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a signifcantly better DFS compared to those with high-grade patterns (p=0.034), and it was similar to T2a (p=0.839). Multivariable analysis confrms the role of T descriptor according to high-grade pattern both for OS (p=0.024; HR 1.285 95% CI 1.033–1.599) and DFS (p=0.003; HR 1.196, 95% CI 1.054–1.344, respectively). These results were confrmed after the propensity score matching analysis. Conclusions pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors

Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study

OBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes.METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups.RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008).CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern