Translational lung cancer research最新文献

Background: Different pathological stages of lung adenocarcinoma require different surgical strategies and have varying prognoses. Predicting their invasiveness is clinically important. This study aims to develop a nomogram to predict the invasiveness of lung adenocarcinoma manifesting as ground-glass nodules (GGNs) based on follow-up computed tomography (CT) imaging.

Methods: We retrospectively collected data of 623 GGNs from 601 patients who underwent two follow-up chest CT scans and were confirmed as lung adenocarcinoma by postoperative pathology between June 2017 and August 2023. These patients were randomly divided into training and testing sets in a 7:3 ratio. Eighty-seven GGNs from 86 patients who underwent surgery between September 2023 and April 2024 were prospectively collected as a validation set. The volume, mean density, solid component volume (SV), percentage of solid component (PSC), and mass of GGNs were evaluated using the InferRead CT Lung software. Patients were classified into Group A (atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma) and Group B (invasive adenocarcinoma). Three predictive models were established: model 1 utilized clinical characteristics and morphological features on pre-surgical CT, model 2 incorporated clinical characteristics, morphological features and quantitative parameters on pre-surgical CT, and model 3 utilized all selected features on baseline and pre-surgical CT.

Results: Model 3 achieved a satisfying area under the curves values of 0.911, 0.893, and 0.932 in the training, testing, and validation sets, respectively, demonstrating superior predictive performance than model1 (0.855, 0.858, and 0.816) and model2 (0.895, 0.891, and 0.903). A nomogram was constructed based on model 3. Calibration curves showed a good fit, and decision curve analysis showed that the nomogram was clinically useful.

Conclusions: The nomogram based on morphological features and quantitative parameters from follow-up CT images showed good discrimination and calibration abilities in predicting the invasiveness of lung adenocarcinoma manifesting as GGNs.

Background: Detailed clinical data about combination treatment with MET inhibitor (METi) and EGFR inhibitor (EGFRi) is lacking in patients with EGFR-mutant, MET-amplified, and EGFRi-resistant non-small cell lung cancer (NSCLC). This study aimed to report longitudinal data on the efficacy and safety of this combination treatment.

Methods: We retrospectively analyzed 44 patients with advanced EGFR-mutant and MET-amplified NSCLC who were treated with any types of METi plus EGFRi after progression with EGFRi at the National Cancer Center Hospital. Longitudinal clinicogenomic data and plasma circulating tumor DNA (ctDNA) data were collected.

Results: The overall response rate was 74.4% and median progression-free survival (PFS) was 5.3 months [95% confidence interval (CI): 3.3-7.3]. Twenty-three patients (52.3%) required either or both treatment discontinuation due to adverse effects. The main cause of discontinuation was pneumonitis (69.2%). There was no significant difference in the PFS of patients with or without METi discontinuation [hazard ratio (HR), 0.93; 95% CI: 0.49-1.78; P=0.83]. Median clearance time of MET amplification in plasma ctDNA was measured as 63 days. Patients who stopped METi within 63 days of initiation showed poorer PFS compared to those who discontinued after (HR, 2.78; 95% CI: 1.00-7.75; P=0.050). Diverse resistance mechanisms including on-target mutations in MET (D1246H) and EGFR (C797S or T790M) were detected in 14 patients. One MET D1246H-mutant case and one EGFR C797S-mutant case responded to sitravatinib and amivantamab, respectively.

Conclusions: A combination of METi and EGFRi showed a promising anti-tumor effect in advanced EGFR-mutant and MET-amplified NSCLC. Pneumonitis was the main adverse effects leading to treatment discontinuation. Early discontinuation of METi negatively affected the survival outcomes.

Background: Lung cancer screening with low-dose computed tomography has been started in some high-income countries and is being considered in others. In many settings uptake remains low. Optimal strategies to increase uptake, including for high-risk subgroups, have not been elucidated. This study used a system dynamics approach based on expert consensus to identify (I) the likely determinants of screening uptake and (II) interactions between these determinants that may affect screening uptake.

Methods: Consensus data on key factors influencing screening uptake were developed from existing literature and through two stakeholder workshops involving clinical and consumer experts. These factors were used to develop a causal loop diagram (CLD) of lung cancer screening uptake.

Results: The CLD comprised three main perspectives of importance for a lung cancer screening program: participant, primary care, and health system. Eight key drivers in the system were identified within these perspectives that will likely influence screening uptake: (I) patient stigma; (II) patient fear of having lung cancer; (III) patient health literacy; (IV) patient waiting time for a scan appointment; (V) general practitioner (GP) capacity; (VI) GP clarity on next steps after an abnormal computed tomography (CT); (VII) specialist capacity to accept referrals and undertake evaluation; and (VIII) healthcare capacity for scanning and reporting. Five key system leverage points to optimise screening uptake were also identified: (I) patient stigma influencing willingness to receive a scan; (II) GP capacity for referral to scans; (III) GP capacity to increase patients' health literacy; (IV) specialist capacity to connect patients with timely treatment; and (V) healthcare capacity to reduce scanning waiting times.

Conclusions: This novel approach to investigation of lung cancer screening implementation, based on Australian expert stakeholder consensus, provides a system-wide view of critical factors that may either limit or promote screening uptake.

Background: Brain metastases (BM) are highly prevalent and associated with a poor prognosis in patients with small cell lung cancer (SCLC). However, the evidence regarding the efficacy of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for patients with SCLC and BM remains limited. Therefore, the objective of this study is to evaluate whether the addition of ICIs confers survival benefits for patients with SCLC and BM.

Methods: This retrospective study enrolled patients with SCLC and BM at the Sun Yat-sen University Cancer Center between January 2018 and December 2022. Clinical characteristics were extracted from medical records. Depending on whether ICIs were added to the first-line treatment, the patients were categorized into the chemotherapy group and the chemoimmunotherapy group. The efficacy of these two treatment approaches was analyzed and compared.

Results: A total of 165 patients were enrolled, with 85 in the chemotherapy group and 80 in the chemoimmunotherapy group. The chemoimmunotherapy group showed a tendency towards prolonged intracranial [6.6 vs. 5.9 months, hazard ratio (HR) =0.77; P=0.14] and extracranial (6.9 vs. 6.5 months, HR =0.73; P=0.12) progression-free survival (PFS) and overall survival (OS) (15.6 vs. 14.5 months, HR =0.98; P=0.93) compared to the chemotherapy group. Cox regression analysis identified liver metastases and local treatment for BM as independent prognostic factors for OS in patients. Furthermore, the chemotherapy group and the chemoimmunotherapy group demonstrated similar patterns of initial disease progression.

Conclusions: Adding ICIs to chemotherapy confers modest survival benefits in patients with SCLC and BM.

Background: Antihistamines alleviate the side effects of antitumor drugs and exert antitumor effects. This study aimed to investigate the potential impact of short-term concomitant use of antihistamines with immune checkpoint inhibitor (ICI) therapy on the efficacy and immune-related adverse events (irAEs) of immunotherapy for patients with advanced lung cancer.

Methods: We retrospectively analyzed the medical records of 211 patients diagnosed with advanced primary lung cancer and treated with immunotherapy at Tianjin Medical University Cancer Institute and Hospital between January 1, 2018, and January 1, 2022. Among these patients, 109 who received H1 antihistamine during the infusion of anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies were assigned to the experimental group; meanwhile, the remaining 102 patients who did not receive H1 antihistamines were assigned to the control group. Balancing was achieved through inverse probability of treatment weight (IPTW) estimation. The data were analyzed using Kaplan-Meier curves and Cox regression analyses.

Results: The median progression-free survival (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group, while the median overall survival (mOS) was 32.8 months in the experimental group and 18.1 months in the control group. In the experimental group, patients treated with only H1 antihistamines had longer mPFS and mOS compared with those who received H1 plus H2 antihistamines. Similarly, in the control group, patients who did not receive antihistamines had a longer mPFS and mOS than those who only received H2 antihistamines. After conducting multivariate analyses, we found that H1 and H2 antihistamines were respectively identified as good and poor independent prognostic factors for both progression-free survival (PFS) and overall survival (OS). The rates of irAEs in the experimental and control groups were 52.4% and 69.2%, respectively, and grade ≥3 irAEs occurred in 4.5% and 25.9% of patients, respectively.

Conclusions: Concomitant use of H1 antihistamines can improve immunotherapy efficacy and reduce irAEs. Meanwhile, concomitant use of H2 antihistamines is associated with reduced PFS and OS time.

Background: Spread through air spaces (STAS) is significantly associated with decreased overall survival (OS) and reduced recurrence-free survival. However, there are no reliable methods to confirm the presence of STAS before surgery. The sensitivity and specificity of the intraoperative frozen section diagnosis of STAS are not satisfactory. This study sought to determine the clinical, pathological, and computed tomography (CT) features of lung cancer with STAS before surgery to guide treatment decisions.

Methods: The data of 121 patients who were positive for STAS and 121 who were negative for STAS as confirmed by surgery and pathology were collected at Jiangsu Cancer Hospital from January 2020 to December 2022. The differences between the two groups in terms of the clinical, pathological, and CT characteristics were compared.

Results: STAS occurred not only in lung adenocarcinoma (LUAD) (106 of 121, 87.6%), but also in other pathological types of lung cancer (15 of 121, 12.4%). STAS was significantly correlated with pathological invasiveness [pathological differentiation, tumor, node, metastasis (TNM) staging, vascular invasion, and pleural invasion; all P<0.05]. STAS was most common in solid tumors (95 of 121, 78.51%). The receiver operating characteristic (ROC) curve showed that the optimal cut-off value for diagnosing STAS based on diameter is 1.55 cm with a sensitivity of 73.3% and a specificity of 47.9%. The percentage of solid components (PSC) is an independent influencing factor of lung cancer with STAS [odds ratio (OR) =111.27; P<0.05] with an optimal cut-off value of 63%, a sensitivity of 92.5%, and a specificity of 72.7%. In the part-solid nodules, the occurrence rate of STAS increased as the PSC increased. STAS was only observed in part-solid nodules with a PSC greater than 25%. Among the CT morphological features, lobulation was an independent influencing factor of lung cancer with STAS (OR =3.513; P<0.05), and persistent indistinct margin ground-glass opacity around the primary lesion of lung cancer (21 of 121, 17.36%) and satellite foci (9 of 121, 7.44%) strongly indicated the existence of STAS.

Conclusions: The clinical, pathological and CT features of STAS may guide clinicians to develop appropriate strategies and improve the survival rate of patients.

Background and objective: The standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions is targeted therapy using tyrosine kinase inhibitors (TKIs). However, data are still lacking on the use of TKIs as a neoadjuvant or induction approach. Therefore, this narrative review aims to summarize the current knowledge on resectable EGFR-mutant and ALK-fused NSCLC regarding available perioperative treatment regimens and off-label neoadjuvant use of targeted therapy.

Methods: The relevant literature was identified by using PubMed and ClinicalTrials.gov (last search phase June 2024) and was restricted to English language. Peer-reviewed manuscripts but also conference abstracts that did not undergo peer-review were included.

Key content and findings: Patients with EGFR-mutations and ALK-fusions have typically been excluded from available phase III perioperative immunotherapy trials due to lower efficacy and higher toxicity of immunotherapy in those patients. In the adjuvant setting, recent evidence from the phase III ALINA and ADAURA trials demonstrated efficacy and safety of targeted therapy in resected ALK-fused and EGFR-mutant NSCLC. However, to date there is no approval for the use of TKIs as neoadjuvant or induction therapy in those patients. We have therefore identified a number of case series and phase II trials using targeted therapy in resectable EGFR-mutant and ALK-fused NSCLC.

Conclusions: Current evidence suggests that targeted therapies might be effective in patients with resectable EGFR-mutant and ALK-positive NSCLC, but ongoing trials will need to provide further evidence on the safety and efficacy of perioperative TKI therapy.

Background: Platinum-based therapies for patients with advanced non-small-cell lung cancer (NSCLC) have classically provided overall survival (OS) rates of six to nine months and objective response rates (ORRs) of 20-30%. Whether prior immunotherapy determines a different response to platinum is currently unknown. This study aimed to analyse the current response characteristics to platinum as a second-line treatment for advanced NSCLC (PD-L1 ≥50%) after first-line immunotherapy.

Methods: This retrospective study was conducted at the University Hospital of Salamanca (CAUSA) between 2016 and 2023 with patients who had advanced NSCLC (PD-L1 ≥50%) treated with second-line platinum-based therapies after immunotherapy (without mutations in EGFR, ALK or ROS1 and with Eastern Cooperative Oncology Group (ECOG) ≤1 during the first- and second-line treatments). Survival and response correlation analyses (Kaplan-Meier and log rank tests in SPSS v. 25) were performed. Subsequently, the results were compared with historical cohorts (PubMed, COCHRANE, ScienceDirect, Embase, and the clinical trial registry) who had received platinum-based therapies for advanced NSCLC.

Results: Seventeen patients were analysed (11 male and 6 female). Their median age was 67 years (interquartile range, 50-77 years). Fifteen patients (88.2%) were smokers or former smokers. The patients' main histology was adenocarcinoma (9 patients, 52.9%). All first-line treatments applied pembrolizumab (median dose: 12 cycles). Second-line platinum-based therapy achieved OS of 25 months (95% CI: 7-45 months) and progression-free survival (PFS) of 6 months (95% CI: 2.5-95 months). The ORR was 47.1% [seven patients with a partial response (PR) and one patient with a complete response (CR)]. Of the patients with PRs or CRs, 75% were treated with platinum plus pemetrexed. The one-year survival rate was 58.8%. The historical OS for first-line platinum-based doublets is 7 to 12 months, with PFS of three to five months and an ORR of 17-30%.

Conclusions: The current response to second-line platinum-based therapies for patients with advanced NSCLC after immunotherapy appears to achieve favourable response rates and be an optimal treatment after progression to immunotherapy. Prior immunotherapy appears to enhance these patients' platinum response, though future confirmatory studies are necessary.

Background: The intricate interplay between inflammation and lung cancer has long been recognized by large number of studies, yet a comprehensive understanding of this relationship remains elusive. There is a clinical need to elucidate the role of tertiary lymphoid structures (TLSs) in lung cancer, particularly their impact on prognosis and therapy. This study aims to address these gaps by conducting a bibliometric analysis to explore the correlations between lung cancer, inflammation, and TLS, highlighting collaborative networks, publication trends, and emerging research directions.

Methods: This study conducted a comprehensive bibliometric analysis of academic literature on lung cancer and inflammation from 2013 to 2023 using the Web of Science Core Collection database. The search strategy "topic (TS) = ('lung cancer') AND TS = (inflammation)" yielded 5,470 records, which were refined through exclusion criteria to 1,284 relevant studies. The inclusion process involved excluding non-English studies and non-original articles or reviews, followed by a relevance check based on titles and abstracts. The bibliometric indicators were calculated based on a transparent and repeatable methodology to ensure the integrity of the findings.

Results: The investigation encompassed 1,284 selected studies, revealing an escalating publication trend since 2013. The interdisciplinary scope of research is apparent, with contributions from 54 countries, with China at the forefront. In-depth author and journal analyses exposed key contributors like Zhang L and influential journals like "Lung Cancer". Co-citation networks illuminated crucial references, clusters, and evolving themes over time, underscoring the intricate relationship between inflammation, cancer, and TLS. TLS as a key component of immune response and inflammation, studying its mechanism of impact on cancer will be a potential research direction in the future.

Conclusions: This study underscores the pivotal role of inflammation in lung cancer progression, mediated by a delicate balance of immune responses. The emerging prominence of TLS as indicator of adaptive immune responses within the tumor microenvironment (TME) offers intriguing avenues for future research and therapeutic interventions. However, limitations in the current research, such as the need for more longitudinal studies and clinical trials, must be addressed. The insights gained from this bibliometric analysis can inform clinical practices and guide future investigations into novel strategies to improve patient outcomes.