Lucheng Zhu

This study aims to investigate the impact of radiotherapy combined with hyperthermia (RHT) on the incidence of radiation pneumonitis (RP) in patients with thoracic malignancies. This study enrolled 233 patients with thoracic malignancies admitted from 2017 to 2020 as the subjects of observation. According to different treatment regimens, patients were divided into the RHT group (N = 114) and the radiotherapy group (RT) (N = 119). The follow-up phase lasted three months before the start of radiotherapy and continued for six months after treatment. Evaluate and compare the incidence of RP in both groups. In individuals with a lung volume receiving more than 20 Gy (V20 > 20%), the incidence of grade ≥ 2 RP was observed to be 33.33% in the RHT group, compared to 55.32% in the RT group. This difference was statistically significant (P = 0.034). Furthermore, there was a significant difference between the number of hyperthermia times and the incidence of RP (P = 0.043). Multivariate analysis revealed that factors such as gender, performance status (PS) score, and the number of hyperthermia times were significantly associated with the incidence of grade ≥ 2 RP. In patients with V20 > 20%, hyperthermia can significantly reduce the incidence of grade ≥ 2 RP in patients undergoing thoracic radiotherapy.

Objectives Patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) are at a heightened risk of developing brain metastases (BM). EGFR-tyrosine kinase inhibitors (TKI) are standard treatment for EGFR-mutated NSCLC. However, the necessity and optimal approach of brain radiotherapy for NSCLC patients with EGFR mutation remain inconclusive. We aimed to answer these questions by retrospectively analyzing the efficacy of radiotherapy in patients with BM from NSCLC with EGFR mutations. Methods Patients with EGFR- mutant NSCLC and BMs who were diagnosed between January 1, 2018 and December 31, 2022 were included. According to treatment methods those patients were divided into whole brain radiotherapy (WBRT) plus EGFR-TKI (WBRT group), stereotactic radiotherapy (SRT) plus EGFR-TKI (SRT group) and EGFR-TKI alone (TKI-only group). Propensity-score-matching (PSM) was performed to minimize the effect of possible confounding factors and to balance treatment groups. Results A total of 142 patients were included in this study. The median follow-up time was 22 months (range, 3.0–43.0 months). In the PSM cohort, the median intracranial progression free survival (iPFS) was 14, 30, 12 months and the median overall survival (OS) was 27 months, not reach and 33 months in WBRT group, SRT group and TKI-only group, respectively. Compared with the other two groups, SRT group significantly improved iPFS and OS (p < 0.05). And the local progression rate of intracranial lesions in SRT group was significantly reduced (p < 0.05). Conclusion This study showed that SRT combined with TKI may improve iPFS and prolong survival in patients with EGFR mutations in BMs from NSCLC.

Lung cancer remains the leading cause of cancer-related deaths globally. In China, nearly half of non-small cell lung cancer (NSCLC) patients carry epidermal growth factor receptor (EGFR) mutations. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the prognosis for patients with EGFR mutations and are considered the preferred treatment for these individuals. Programmed death-ligand 1 (PD-L1) expression levels are now widely used as a biomarker to predict the effectiveness of PD-1/PD-L1 immunotherapy in NSCLC. Additionally, the impact of PD-L1 expression on the efficacy of EGFR-TKIs has garnered considerable attention from researchers. This review explores recent studies on the epidemiology and clinical outcomes associated with PD-L1 in NSCLC patients harboring driver gene mutations.

Background: Lung cancer is a common cause of brain metastases, approximately 40% of patients with lung cancer will develop brain metastases at some point during their disease. Hypofractionated stereotactic radiotherapy (HSRT) has been demonstrated to be effective in controlling limited brain metastases. However, there is still no conclusive on the optimal segmentation of HSRT. The aim of our study was to explore the correlation between the HSRT dosage and its treatment effect and toxicity. Methods: A retrospective analysis was conducted on patients with non-small cell lung cancer (NSCLC) brain metastasis at Hangzhou Cancer Hospital from 1 January 2019 to 1 January 2021. The number of brain metastases did not exceed 10 in all patients and the number of fractions of HSRT was 5. The prescription dose ranges from 25 to 40 Gy. The Kaplan–Meier method was used for estimation of the localised intracranial control rate (iLC). Adverse radiation effects (AREs) were evaluated according to CTCAE 5.0. This study was approved by the Institutional Ethics Review Board of the Hangzhou Cancer Hospital (#73/HZCH-2022). Results: Forty eligible patients with a total of 70 brain metastases were included in this study. The 1-year iLC was 76% and 89% in the prescribed dose ≤ 30 Gy and > 30 Gy group, respectively (P < 0.05). For patients treated with HSRT combined with targeted therapy, immunotherapy and chemotherapy, the 1-year iLC was 89%, 100%, and 45%, respectively. No significant associations were observed between the number, maximum diameter, location, and type of pathology of brain metastases. The rate of all-grade AREs was 33%. Two patients who received a total dose of 40 Gy developed grade 3 headache, the rest of the AREs were grade 1–2. Conclusions: Increasing the prescription dose of HSRT improves treatment effect but may also exacerbate the side effects. Systemic therapy might impact the iLC rate, and individualized treatment regimens need to be developed.

Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8⁺ T lymphocytes at baseline was the independent risk factor for the onset of irAEs (p = 0.008). A higher level of CD8⁺ T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, p < 0.001) and OS (27.9 months vs. 11.7 months, p = 0.014). Furthermore, patients who had higher baseline CD8⁺ T lymphocytes and experienced irAEs had a longer PFS (18.4 months vs. 2.2 months, p < 0.001) and OS (32.8 months vs. 9.0 months, p = 0.001) than those who had lower CD8+ T lymphocytes and no irAEs. Our study highlights the value of baseline peripheral CD8⁺ T lymphocytes as a predictive factor for irAEs in advanced NSCLC patients receiving ICIs. In addition, patients who have higher baseline CD8⁺ T lymphocytes and experience irAEs would have a superior PFS and OS.

Background: Concurrent chemo-radiotherapy remains the standard treatment in unresectable stage III non-small-cell lung cancer (NSCLC) patients. Several studies have shown a potential value of concurrent epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with thoracic radiotherapy in EGFR-mutated population, but a high risk of radiation pneumonitis raised a major concern. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI, with radiotherapy in locally advanced EGFR-mutated NSCLC patients. Methods: Locally advanced NSCLC patients harboring sensitive EGFR mutation will be included in this study. A radiotherapy plan will be made for each patient before treatment, and the lung V20 will be calculated. Patients with lung V20 ≥ 28% were enrolled in induction group (arm A), which almonertinib was given for 2 months followed by concurrent radiotherapy; patients with lung V20 < 28% were enrolled in concurrent group (arm B), which almonertinib was given concurrent with thoracic radiotherapy. The primary endpoint is the incidence of grade ≥ 3 radiation pneumonitis within 6 months post-radiotherapy, and the secondary endpoints are local control rate, progression-free survival, and overall survival. Discussion: The safety and efficacy of third-generation EGFR-TKI concurrent with thoracic radiotherapy in locally advanced EGFR-mutated NSCLC is still unknown. We propose to conduct this phase 2 study evaluating the safety especially the radiation pneumonitis within 6 months post-radiotherapy. This trial protocol has been approved by the Ethics committee of Hangzhou cancer hospital. The ethics number is HZCH-2020-030. Trial registration: clinicaltrials.gov, NCT04636593. Registered 19 November 2020 - Retrospectively registered

Introduction: Radiation pneumonitis (RP) is the most significant dose-limiting toxicity in patients receiving thoracic radiotherapy. The underlying mechanisms of RP are still inconclusive. Our objective was to determine the genes and molecular pathways associated with RP using computational tools and publicly available data. Methods: RP-associated genes were determined by text mining, and the intersection of the two gene sets was selected for Gene Ontology analysis using the GeneCodis program. Protein-protein interaction network analysis was performed using STRINGdb to identify the final genes. Results: Our analysis identified 256 genes related to RP with text mining. The enriched biological process annotations resulted in 47 sets of annotations containing a total of 156 unique genes. KEGG analysis of the enriched pathways identified 24 pathways containing a total of 41 unique genes. The protein-protein interaction analysis yielded 23 genes (mostly the PI3K family). Conclusion: Gene discovery using in silico text mining and pathway analysis tools can facilitate the identification of the underlying mechanisms of RP.