RESUMO
OBJECTIVE: To compare characteristics, disease course, and prognosis of spontaneous versus iatrogenic benign metastasizing leiomyoma (BML). METHODS: A retrospective cohort study comparing iatrogenic and spontaneous BML. RESULTS: Twenty cases were included, 12 (60%) spontaneous and 8 (40.0%) iatrogenic with a median follow up of 3.4 years. The rate of asymptomatic presentation did not differ between study groups (P = 0.157). When symptoms occurred, dyspnea was more common in the spontaneous group (66.6% vs 0%, P = 0.023) and self-palpation was more common in the iatrogenic group (57.1% vs 0%, P = 0.023). Intravascular masses were more common in the spontaneous group (66.6% vs 0%, P = 0.029). Rate of BML located in abdominal/pelvic cavity was higher in the iatrogenic group (100.0% vs 41.6%, P = 0.014). Of the 12 women in the spontaneous group, 50% had recurrent disease following surgical resection or unresectable lesions surgical resection was successfully attempted in seven of the eight (87.5%) women in the iatrogenic group, with no residual/recurrent disease. None of the patients died of her disease. CONCLUSION: Spontaneous and iatrogenic BML can probably be regarded as two separate etiologies of the same pathologic phenomenon, usually with favorable prognosis. However, spontaneous BML may have a less favorable course.
Assuntos
Leiomioma , Neoplasias Pulmonares , Neoplasias Uterinas , Feminino , Humanos , Leiomioma/patologia , Leiomioma/cirurgia , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgiaRESUMO
The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal , Melanoma/terapia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/terapia , Adulto , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Imunoterapia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
Omics analyses often result in dozens to hundreds of potential targets, requiring validation for their biological relevance. Current high-throughput functional investigation methods are frequently labor-intensive, expensive, and display low reproducibility. The Immune Co-Culture Cell Microarray (ICCM) is a formalin-fixed paraffin-embedded cell block microarray based on co-cultures of patient-derived tumor-infiltrating lymphocytes and their autologous melanoma cells. Each ICCM slide represents the same experiment and can be stained using standard immunohistochemistry and immunofluorescence techniques. Functional dynamics assessment of both proteins and microRNAs using ICCM stained slides demonstrated similar findings to flow cytometry assays and to previously published patient-derived biopsy reports.
Assuntos
Neoplasias , Técnicas de Cocultura , Humanos , Linfócitos , Linfócitos do Interstício Tumoral , Reprodutibilidade dos TestesRESUMO
After the publication of the original article [1], we were notified the upper panel of the Fig. 1, where the patients' codes are listed, was cropped by mistake so the patients 1-8 are repeated.
RESUMO
BACKGROUND: Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~ 1%) but are relatively common (10-50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. Little is known about the incidence and clinical implication of these mutations in early recurrence events, such as local recurrences or newly diagnosed metastatic disease. METHODS: We collected 130 archival tumor samples from 103 breast cancer patients treated with endocrine therapy prior to their local/metastatic recurrence. The cohort consisted of 41 patients having at least 1 sample from local/loco-regional recurrence and 62 patients with metastatic disease (of whom 41 newly diagnosed and 28 with advanced disease). The 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) were analyzed either by targeted sequencing or by droplet digital PCR. Progression-free survival (PFS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were statistically tested by Kaplan-Meier analysis. RESULTS: The prevalence of ESR1 mutations was 5/41 (12%) in newly diagnosed metastatic patients and 5/28 (18%) for advanced metastases, detected at allele frequency > 1%. All mutations in advanced metastases were detected in patients previously treated with both tamoxifen (TAM) and aromatase inhibitors (AI). However, in newly diagnosed metastatic patients, 4/5 mutations occurred in patients treated with TAM alone. PFS on AI treatment in metastatic patients was significantly shorter for ESR1 mutation carriers (p = 0.017). In the local recurrence cohort, ESR1 mutations were identified in 15/41 (36%) patients but only 4/41 (10%) were detected at allele frequency > 1%. Again, most mutations (3/4) were detected under TAM monotherapy. Notably, 1 patient developed ESR1 mutation while on neoadjuvant endocrine therapy. DFS and DRFS were significantly shorter (p = 0.04 and p = 0.017, respectively) in patients that had ESR1 mutations (> 1%) in their loco-regional recurrence tumor. CONCLUSIONS: Clinically relevant ESR1 mutations are prevalent in newly diagnosed metastatic and local recurrence of endocrine-treated breast cancer. Since local recurrences are amenable to curative therapy, these mutations may inform the selection of subsequent endocrine therapies.