Macrophage plays an important role in homeostasis and immunity, and dysfunctional macrophage polarization is believed to be associated with the pathogenesis of tissue fibrosis and tumor progression. Colony stimulating factor-1 (CSF-1), a polypeptide chain cytokine, through its receptor (CSF-1R) regulates the differentiation of macrophages. Recently, the promising therapeutic potential of CSF-1/CSF-1R signaling pathway inhibition in cancer treatment is widely used. Furthermore, inhibition of CSF-1/CSF-1R signaling combined with radiotherapy has been extensively studied to reduce immunosuppression and promote abscopal effect. In addition, cumulative evidence demonstrated that M2 phenotype macrophage is dominant in tissue fibrosis and the inhibition of CSF-1/CSF-1R signaling pathway ameliorated pulmonary fibrosis, including radiation-induced lung fibrosis. Herein, we provide a comprehensive review of the CSF-1/CSF-1R signaling pathway in radiotherapy, with a focus on advances in macrophage-targeted strategies in the treatment of cancer and pulmonary fibrosis.

Radiotherapy is one of the most important treatments for chest tumours. Although there are plenty of strategies to prevent damage to normal lung tissues, it cannot be avoided with the emergence of radiation‐induced lung injury. The purpose of this study was to investigate the potential radioprotective effects of glucosamine, which exerted anti‐inflammatory activity in joint inflammation. In this study, we found glucosamine relieved inflammatory response and structural damages in lung tissues after radiation via HE staining. Then, we detected the level of epithelial‐mesenchymal transition marker in vitro and in vivo, which we could clearly observe that glucosamine treatment inhibited epithelial‐mesenchymal transition. Besides, we found glucosamine could inhibit apoptosis and promote proliferation of normal lung epithelial cells in vitro caused by radiation. In conclusion, our data showed that glucosamine alleviated radiation‐induced lung injury via inhibiting epithelial‐mesenchymal transition, which indicated glucosamine could be a novel potential radioprotector for radiation‐induced lung injury.

Background and Purpose: About 70% of patients with radical surgery Cholangiocarcinoma (CCA) have recurrence and metastasis. There are few studies on the relationship between CCA adjuvant chemotherapy (mono or combined therapy), recurrence pattern (local, regional, distant recurrence) and prognosis [(Disease free survival, DFS), (Overall survival, OS)] after radical surgery. This study focuses on the correlation between CCA adjuvant chemotherapy, recurrence pattern and prognosis. Methods: The study involved retrospective analysis of data: preoperative hematology, clinical pathology, adjuvant chemotherapy regimens, recurrence pattern, DFS and OS, of 207 patients with CCA. Chi-square test was used to analyze the correlation between related factors and postoperative recurrence. Survival curves were plotted by Kaplan-Meier method, P-values were calculated by Log-rank for univariate analysis, multivariate COX regression method for multivariate analysis. Results: Using chi-square test, there were correlations between high carbohydrate antigen 19-9 level(CA19-9≥35), vascular invasion, single-agent adjuvant chemotherapy and postoperative recurrences (p=0.04, p=0.04, p=0.02), COX multivariate regression analysis showed that adjuvant chemotherapy (single vs. doublet drug regimen) was an independent prognostic factor for DFS (11.0 vs. 24.6 months, HR=2.88, P=0.01), whereas recurrence pattern (local vs. distant; regional vs. distant) was an independent prognostic factor for OS (31.2 months vs. 20.4 months, HR=0.58, p=0.01; 32.0 months vs. 20.4 months, HR=0.51, p=0.01). Conclusion: Adjuvant chemotherapy regimen was an independent prognostic factor of DFS, whereas recurrence patterns were independent prognostic factors for OS. adjuvant chemotherapy with doublet drug regimen was correlated with longer DFS, and different recurrence modes affect OS.

Background: This study aimed to determine whether the immune prognostic index (ECIPI), based on hemoglobin (Hb) and neutrophil‐to‐lymphocyte ratio (NLR), could predict the prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving programmed cell death‐1 (PD‐1) inhibitor treatment.Methods: Advanced ESCC patients who had been treated with PD‐1 inhibitors from Jan 2016 to Oct 2021 were included. Kaplan–Meier method and Cox proportional hazards regression were used to analyze progression‐free survival (PFS) and overall survival (OS). The overall response rate (ORR) was the percentage of complete and partial responses. Univariate and multivariate analyses were used for estimating hazard ratio (HR) and 95% confidence interval (CI). Patients were grouped by ECIPI (good: Hb > 105 g/L and NLR ≤ 4.3; intermediate: Hb ≤ 105 g/L and NLR ≤ 4.3, or Hb > 105 g/L and NLR < 4.3; poor: Hb ≤ 105 g/L and NLR > 4.3). Variables for the multivariate model were selected if the p‐value was below 0.05 in the univariate analysis. All statistical comparisons were two‐way, and a p‐value below 0.05 was set as statistical significance.Results: Totally, of 123 ESCC patients with stage III or IV were included in the study. Efficacy evaluation showed that patients with pretreatment ECIPI good had the best ORR compared with those with ECIPI intermediate and ECIPI poor (53% vs. 22% vs. 8%, p < 0.01). Multivariate analysis showed that ECIPI was an independent influential factor for PFS (p = 0.004) and OS (p < 0.001). Kaplan–Meier curves demonstrated that patients with ECIPI good had the longest PFS (median: 11.6 vs. 3.5 vs. 1.7 months, p < 0.0001) and OS (median: 23.6 vs. 16.7 vs. 4.0 months, p < 0.0001) compared with those with ECIPI intermediate and ECIPI poor. Subgroup analysis indicated that ECIPI good was associated with improved PFS and OS in patients with ECOG 0–1, PD‐1 inhibitor plus chemotherapy, first‐line treatment, and smoke (all p < 0.05).Conclusions: Pretreatment ECIPI was associated with the prognosis in advanced ESCC patients with anti‐PD‐1 therapy, suggesting that ECIPI may be a useful tool to identify patients likely sensitive to PD‐1 inhibitors.

Ultra-high dose rate (FLASH) radiotherapy is a novel modality delivering dose rates several orders of magnitude higher than conventional dose rate (CONV) radiotherapy. FLASH radiotherapy has been shown to significantly reduce the damaging effects on normal tissues while achieving similar tumor control, a phenomenon referred to as the FLASH effect. Radiation-induced lung injury (RILI) represents a prevalent complication in thoracic tumor radiotherapy, significantly compromising treatment outcomes and patient quality of life. Emerging preclinical evidence consistently demonstrates that FLASH radiotherapy significantly attenuates radiation-induced lung injury compared to CONV radiotherapy. The observed radioprotection primarily manifests in structural preservation of alveolar epithelium, pulmonary vasculature, and bronchial networks, concomitant with substantial reductions in both radiation pneumonitis and subsequent pulmonary fibrosis. Current evidence suggests that RILI pathogenesis involves multiple mechanisms, including DNA damage and repair, reactive oxygen species (ROS) and oxidative stress, inflammation, and immune response. These mechanistic insights provide a crucial foundation for investigating the radiobiological basis of the FLASH effect. Our review summarizes the preclinical studies of FLASH radiotherapy in mitigating lung injury. Furthermore, it explores the potential mechanisms underlying the FLASH effect from the perspective of the biological mechanism of RILI, aiming to provide a reference and direction for the clinical translation of FLASH radiotherapy.

Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive malignancy with an extremely poor prognosis. For a long time, platinum-based chemotherapy combined with etoposide has been the primary treatment option. Although the initial response rate is high, the vast majority of patients face the dilemma of rapid recurrence and drug resistance. In recent years, the application of immunotherapy has brought about a significant breakthrough in the treatment of ES-SCLC. Multiple Phase III clinical trials have demonstrated that combining immune checkpoint inhibitors with traditional chemotherapy regimens as first-line treatment significantly improves the median overall survival (OS) and progression-free survival (PFS) in patients, while maintaining manageable safety profiles. Therefore, chemotherapy combined with immunotherapy has become the new standard for first-line treatment of ES-SCLC worldwide. However, the absolute survival benefit from immunotherapy remains limited. Against this backdrop, thoracic radiotherapy (TRT), as an effective local treatment modality, shows potential for further survival gains. The combination of chemoimmunotherapy and TRT is emerging as a key area of current clinical exploration. However, the characteristics of the patient population that may benefit most from this treatment modality, as well as the optimal dose and timing of TRT, remain under investigation. Furthermore, the predictive value of previously discussed biomarkers in this combination therapy strategy for ES-SCLC remains unclear. Therefore, this paper reviewed recent advances in treatment strategies and candidate biomarkers for ES-SCLC, with a particular focus on the evolving role of thoracic radiotherapy in the era of immunotherapy.