Zhongshan Liu

Objective: To evaluate the dosimetry, efficacy and safety of individualized 3-dimensional (3D)-printed applicator for interstitial brachytherapy (ISBT) compared to the freehand ISBT in locally advanced cervical cancer (LACC). Methods: This retrospective study included 100 patients with LACC who underwent concurrent chemoradiotherapy at our institution between January 2020 and December 2024. Among them, 49 patients received ISBT using 3D-printed applicators, and 51 underwent freehand ISBT. The high-risk clinical target volume (HR-CTV) D90 and D2cc for organs at risks were compared between the two groups. The survival outcomes and treatment-related complications were assessed. Results: The HR-CTV D90 was significantly higher in the 3D-printed group than in the freehand group (91.27 ± 1.76 Gy vs. 89.33 ± 1.72 Gy, P < 0.001), while bladder and rectum D2cc were significantly lower (83.77 ± 2.03 Gy vs. 85.37 ± 1.81 Gy, P < 0.001; 70.26 ± 1.87 Gy vs. 72.01 ± 1.53 Gy, P < 0.001). And a lower sigmoid D2cc trend was observed in the 3D-printed group (68.07 ± 2.07 Gy vs. 68.69 ± 1.50 Gy, P = 0.09). The incidence of treatment-related complications did not differ significantly between the two groups. The 3-year overall survival (71.5% vs. 69.8%; P = 0.79) and 3-year disease-free survival (71.7% vs. 67.0%; P = 0.80) rates were comparable between the 3D-printed and freehand groups. However, the 3D-printed group showed significantly improved 3-year local recurrence-free survival (86.5% vs. 67.0%; P = 0.04). Conclusion: Compared to freehand ISBT, the 3D-printed ISBT provides superior dosimetric outcomes with a favorable safety. Clinical trial number: Not applicable.

The tumor microenvironment (TME) is a complex and dynamic ecosystem composed of tumor cells, immune cells, supporting cells, and the extracellular matrix. Typically, the TME is characterized by an immunosuppressive state. To meet the demands of rapid proliferation, cancer cells undergo metabolic reprogramming, which enhances their biosynthesis and bioenergy supply. Immune cells require similar nutrients for activation and proliferation, leading to competition and immunosuppression within the TME. Additionally, tumor metabolites inhibit immune cell activation and function. Consequently, an immunosuppressed and immune-tolerant TME promotes cancer cell proliferation and metastasis. Long non-coding RNAs (lncRNAs), a category of non-coding RNA longer than 200 nucleotides, regulate tumor metabolic reprogramming by interacting with key enzymes, transporters, and related signaling pathways involved in tumor metabolism. Furthermore, lncRNAs can interact with both cellular and non-cellular components in the TME, thereby facilitating tumor growth, metastasis, drug resistance, and inducing immunosuppression. Recent studies have demonstrated that lncRNAs play a crucial role in reshaping the TME by regulating tumor metabolic reprogramming. In this discussion, we explore the potential mechanisms through which lncRNAs regulate tumor metabolic reprogramming to remodel the TME. Additionally, we examine the prospects of lncRNAs as targets for anti-tumor therapy and as biomarkers for tumor prognosis.

Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. In the tumor microenvironment (TME), Cu²⁺ combines with H₂O₂ to produce O₂ that is reduced to Cu¹⁺ by glutathione (GSH), causing a Fenton-like reaction that reduces tumor hypoxia and simultaneously generates ROS to eliminate tumor cells in conjunction with PTT/PDT. Compared with other therapeutic modalities, PTT/PDT can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs. Herein, we reviewed and briefly summarized the mechanisms of actions of tumor-targeted PTT/PDT and the role of Cu, generated from Cu-based NMs, in PTs. Furthermore, we described the Cu-based NMs used in PTT/PDT applications.

Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%–2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients’ survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Copper serves as a vital microelement which is widely present in the biosystem, functioning as multi-enzyme active site, including oxidative stress, lipid oxidation and energy metabolism, where oxidation and reduction characteristics are both beneficial and lethal to cells. Since tumor tissue has a higher demand for copper and is more susceptible to copper homeostasis, copper may modulate cancer cell survival through reactive oxygen species (ROS) excessive accumulation, proteasome inhibition and anti-angiogenesis. Therefore, intracellular copper has attracted great interest that multifunctional copper-based nanomaterials can be exploited in cancer diagnostics and antitumor therapy. Therefore, this review explains the potential mechanisms of copper-associated cell death and investigates the effectiveness of multifunctional copper-based biomaterials in the field of antitumor therapy.

A compelling set of links between chemotherapyor radiation-induced intestinal inflammation and microbial dysbiosis has emerged. It is the proportional imbalance between pathogenic and beneficial bacteria that aggravates intestinal mucositis. Bacteria that ferment fibers and produce short-chain fatty acids (SCFAs), (such as acetate, propionate, and butyrate) are typically reduced in the mucosa and feces of patients undergoing cancer therapy. In contrast, increasing lipopolysaccharide-producing bacteria result in proinflammatory events by interacting with Toll-like receptors. A collective acceptance is that bacterial metabolites are critical in recovering intestinal homeostasis. We herein review evidence supporting the positive roles carried out by SCFAs. SCFAs, acting as signaling molecules, directly activate G-coupled-receptors and inhibit histone deacetylases. Thus, SCFAs are able to strengthen the gut barrier and regulate immunomodulatory functions. Furthermore, it is possible to reverse intestinal microbial dysbiosis and subsequently suppress the secretion of proinflammatory cytokines by directly applying SCFA-producing bacteria. In addition, anticancer effects of SCFAs have proved in the colorectal cancer. In this review, we discuss microbial dysbiosis and its impact on chemotherapyor radiation-induced intestinal mucositis. Moreover, we summarize the mechanisms of SCFA production and its effects on intestinal mucositis. This review suggests the therapeutic potential of SCFAs for the management of chemotherapyor radiation-induced intestinal inflammation.