RESUMEN
Giant cell tumor of bone (GCTB) is a rare borderline tumor which can develop lung metastasis. Guidelines for patients with multiple pulmonary metastases recommend systemic therapies, such as denosumab and interferons (IFNs). However, when both of these treatment approaches fail, no satisfactory options are available. Thus, additional treatments for GCTB after failure of standard treatment would be beneficial. Here we present a patient with GCTB and multiple pulmonary metastases who was treated with stereotactic body radiotherapy (SBRT) after failure of surgery, denosumab, and bisphosphonates (BPs). This is the first well-documented report of a patient with metastatic GCTB who received lung SBRT after the failure of systemic therapy and achieved a favorable response. Some of the patient's pulmonary metastases were treated using SBRT (44 Gy/4 F). The long diameters of the irradiated nodules decreased 58.2% from baseline in the 30 months after SBRT. Moreover, the peritumoral volume of another nodule also shrank by 29.1% after receiving a low-scatter dose of 7.6 Gy/4 F, which was too small to have induced tumor regression. No obvious adverse events were observed during SBRT or in the follow-up period. Our case provides clinical evidence that SBRT may be a safe and effective method to treat metastatic GCTB and can produce a low-dose radiation-induced abscopal response, suggesting that immune responses can contribute to GCTB regression. In addition, we reviewed publications regarding treatment recommendations, the prospects for SBRT application, and possible effects of abscopal responses on GCTB.
RESUMEN
Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.
RESUMEN
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects multiple organs and is caused by inactive mutations in the TSC1 or TSC2 genes. The main symptoms of TSC are neurocutaneous syndrome and benign hamartoma formation. Notably, malignancy is not an indication of TSC. In this article, we present the case of a 48-year-old female with cervical cancer (CC) combined with TSC, who was misdiagnosed with multiple metastases. Toe masses, pelvic nodules, and multiple osteogenic lesions were initially observed. Multi-site puncture biopsies and a toe amputation were performed; the pathology results did not indicate malignancy. Subsequently, hypomelanotic macules on the back, subependymal nodules (SENs), ungual fibromas, multiple renal cysts, and sclerotic-bone-lesions (SBLs) of the skull, and vertebrae were observed, leading to a diagnosis of TSC. Given that TSC is a benign disease and has not yet caused any organ disfunction, no special treatment was provided to this patient. After a follow-up period of almost 65 months, the patient's quality of life remained good without therapy. Oncologists should pay attention to benign diseases in the face of multiple lesions to reduce misdiagnosis and overtreatment. In addition, TSC may interact with CC through molecular mechanisms, such as the mammalian target of rapamycin (mTOR) pathway.
Asunto(s)
Esclerosis Tuberosa , Neoplasias del Cuello Uterino , Errores Diagnósticos , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Esclerosis Tuberosa/diagnóstico , Proteína 2 del Complejo de la Esclerosis Tuberosa , Neoplasias del Cuello Uterino/diagnósticoRESUMEN
Background: MAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response. Methods: Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation. Results: Compared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment. Conclusions: MAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.