Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignancy worldwide. However, very few established diagnostic biomarkers for HNSCC have been universally applied in clinical practice. Recently, much attention has been paid to extracellular vesicles (EVs) regarding their roles as cancer biomarkers because EVs carry plentiful cargoes, including lipids, proteins, nucleic acids, and metabolites. In HNSCC, several molecules carried by EVs, which are derived from peripheral blood and saliva, have been implicated to be effective in cancer detection, staging, treatment planning, response monitoring, and prognosis prediction. Although several EV molecules have been identified to be significantly correlated with a set of clinicalpathological parameters of HNSCC, several key limitations need to be resolved before the clinical application of EVs as carriers of biomarkers in HNSCC. In this review, we discuss current knowledge in the literature regarding EV-based biomarkers in HNSCC, emphasizing current limitations of their clinical applications.
Basic research on heavy ion cancer therapy such as radiobiology, medical physics, and therapeutic technique has been conducted at the Institute of Modern Physics (IMP), Chinese Academy of Sciences since 1995. Based on the achievements acquired in the basic research and the requirements for a heavy ion accelerator for radiotherapy purposes, a dedicated heavy ion therapy facility named Heavy Ion Medical Machine (HIMM) was designed at IMP and constructed in Wuwei, China. The HIMM facility consists of two electron cyclotron resonance ion sources, one cyclotron as the injector and one synchrotron as the main accelerator, and four different treatment rooms equipped with passive or active beam delivery systems, and accelerates carbon ions up to 400 MeV/u. After the performance inspection of HIMM organized by the National Medical Device Inspection Center, preclinical tests like cell and animal radiobiological experiments and dosimetric verification using anthropomorphic phantoms for elucidating the biophysical properties of the carbon ion beams provided by HIMM were carried out. According to the Chinese medical device regulations, a clinical trial in which 46 tumor patients were recruited and two hospitals participated was conducted in the HIMM facility, aiming at evaluating the treatment safety and short-term efficacy of the medical device. The success of the clinical trial helped the HIMM facility be authorized by the Chinese government as a class III medical device. In this paper, all the aspects mentioned above are introduced and discussed, and implications for future improvements are also given.
Background: Hepatocellular carcinoma (HCC) is a common disease in human history and one of the main causes of cancer-related death. Insufficient oxygen supply in the tumor microenvironment forces cancer cells to survive in a mild hypoxia environment. Fibroblast growth factor 21 (FGF21), a member of the FGF family, has become the focus of public attention due to its outstanding achievements in diabetes and lipid lowering. However, the mechanism of FGF21 in HCC remains unclear.
Objective: The aims of this study were to clarify whether or not FGF21 could increase the sensitivity of sorafenib (SORA) to HCC under hypoxia and explore the possible mechanism.
Methods: In this study, by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide cell viability test, plate clone formation test, western blot analysis, Hoechst/propidium iodide double staining experiment, flow cytometry, quantitative reverse transcription polymerase chain reaction, and subcutaneous tumor transplantation in mice, we studied the effects of recombinant human FGF21 combined with SORA on hepatoma cells in vitro and in vivo. FGF21 could enhance the phosphorylation of mothers against decapentaplegic homolog 3 (Smad3) under anaerobic conditions. When combined with SORA, FGF21 could increase the sensitivity of hepatoma cells to SORA and inhibit the growth and migration of hepatoma cells.
Results: FGF21 may increase the sensitivity of HCC to SORA by enhancing the phosphorylation of Smad3 through the phosphatidylinositol 3-kinase/protein kinase B pathway under hypoxia.
Conclusion: Our study suggested the possibility of combination therapy for SORA and FGF21 on HCC.
Objective: This single-center, prospective, observational study was designed to investigate the toxicities, patient-reported outcome (PRO), and dosimetric analysis of whole breast ultrafractionation radiotherapy (RT) after breast-conserving surgery (BCS) in early breast cancer (BC).
Patients and methods: Patients diagnosed with BC stage I, II and treated with BCS were enrolled. A dose of 26 Gray (Gy) in five fractions was prescribed to the whole breast and tumor bed. Clinical endpoints included toxicities, PRO, and dosimetric analysis. PRO was measured by the European Organization for Research and Treatment of Cancer general quality of life questionnaire (EORTC QLQ-C30) and the BC-specific questionnaire (EORTC QLQ-BR23) questionnaires.
Results: Between January 2022 and June 2023, 62 female patients were enrolled. The median age was 45 years. Most patients (83.9%) were diagnosed with pathological stage I disease. The median planning target volume (PTV) was 456.4 mL. The minimum, maximum, and mean doses, and D95 (dose of PTV irradiated volume more than 95%) to PTV were 20.2, 28.8, 27.2, and 26.3 Gy, respectively. The median mean lung dose and percentage lung volume receiving 8 Gy (V8) were 3.6 Gy and 13.4%, respectively. The median mean heart dose, V1.5 (percentage of organ volume irradiated with 1.5 Gy or higher), and V7 (percentage of organ volume irradiated with 7 Gy or higher) were 0.6 Gy, 6.8%, and 0.4%, respectively. Cosmetic effects before RT showed no obvious differences compared to that post RT. No toxicities of grade 3 or higher occurred. Five patients had asymptomatic radiation pneumonia (grade 1), and 12 patients had radiation dermatitis (grade 1). No factor was significantly related to radiation dermatitis or radiation pneumonia. For the EORTC QLQ-C30 and QLQ-BR23 questionnaires, all function and symptom scores before RT had no significant differences compared with that after RT, 1–2 months after RT, and 3–4 months after RT. Ultrafractionation RT did not worsen PRO. The 1-year crude local control was 100%.
Conclusion: Whole breast ultrafractionation RT after BCS in early BC has no severe toxicities and does not affect PRO. These results need to be further validated with a longer follow-up and a larger sample size.
Background: The relationship between the regression and prognosis of melanoma has been debated for years. When competing-risk events are present, using traditional survival analysis methods may induce bias in the identified prognostic factors that affect patients with regressive melanoma.
Methods: Data on patients diagnosed with regressive melanoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database during 2000–2019. Cumulative incidence function and Gray’s test were used for the univariate analysis, and the Cox proportional-hazards model and the Fine–Gray model were used for the multivariate analysis.
Results: A total of 1442 eligible patients were diagnosed with regressive melanoma, including 529 patients who died: 109 from regressive melanoma and 420 from other causes. The multivariate analysis using the Fine–Gray model revealed that SEER stage, surgery status, and marital status were important factors that affected the prognosis of regressive melanoma. Due to the existence of competing-risk events, the Cox model may have induced biases in estimating the effect values, and the competing-risks model was more advantageous in the analysis of multipleendpoint clinical survival data.
Conclusion: The findings of this study may help clinicians to better understand regressive melanoma and provide reference data for clinical decisions.
Objective: To highlight the incidence and management of acute coronary syndrome (ACS) in patients with gastric cancer undergoing immune checkpoint inhibitor (ICI) therapy, emphasizing the need for early detection and intervention in this high-risk population.
Patients and methods: We presented a case of a 71-year-old male patient with poorly differentiated adenocarcinoma of the gastric antrum, clinical stage cT4N2M0, phase III, with no prior history of chronic diseases or cardiovascular risk factors. The patient was treated with a combination of ICI therapy (sintilimab) and chemotherapy using the albumin-bound paclitaxel combined with S1 regimen. Following therapy, he developed symptoms and diagnostic findings consistent with ACS, which was managed with percutaneous coronary stenting.
Results: The patient’s presentation with ACS during ICI therapy underscored the potential cardiovascular risks associated with cancer treatments, particularly in patients without traditional cardiovascular risk factors. Management involved collaboration between oncologists and cardiologists, leading to successful coronary stenting and continuation of antitumor therapy.
Conclusion: ACS is a significant risk in patients with malignancies undergoing ICI therapy, even in those without prior cardiovascular disease. Early recognition and management of ACS in this context are crucial to enable the continuation of cancer treatment and improve patient outcomes. This case underscores the importance of interdisciplinary collaboration in managing complex patients with concurrent cancer and cardiovascular disease.