43 research outputs found

    Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

    Get PDF
    The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers\u27 tissue of origin

    Surgery in Cervical Cancer

    No full text

    Reducing overtreatment: A comparison of lymph node assessment strategies for endometrial cancer

    No full text
    To compare the utility of three lymph node (LN) assessment strategies to identify lymphatic metastases while minimizing complete lymphadenectomy rates in women with low-grade endometrial cancer (EC). Using our institutional standard protocol (SP), patients with complex atypical hyperplasia (CAH) or grade 1/2 EC underwent sentinel lymph node (SLN) mapping, hysterectomy, and intraoperative frozen section (FS). Lymphadenectomy was performed if high-risk uterine features were identified on FS. Utilizing SP data, two alternative strategies were applied: a Universal FS Strategy (UFS), omitting SLN mapping and performing lymphadenectomy based on FS results, and a SLN-Restrictive FS Strategy (SLN-RFS) in which FS and lymphadenectomy are performed only if bilateral SLN mapping fails. Of 114 patients managed on the SP, SLNs were identified in 86%, with lymphatic metastases detected in eight patients. Six patients recurred after a median follow up of 15months. Most (83%) developed in those who had a negative systematic lymphadenectomy (n=4; mean LNs: 18) or no lymphadenectomy indication. When applying the alternative lymphatic assessment strategies, the SLN-RFS approach would theoretically result in lower lymphadenectomy rates compared to both the SP and the alternative UFS strategies (9.2% versus 36.8% and 36.8%, respectively; p=0.004), without a reduction in detection of LN metastases (8/8 versus 8/8 and 5/8, respectively). In this modeling analysis, an operative strategy omitting universal frozen section and restricting its use to cases with failed SLN mapping may result in lower lymphadenectomy rates and reduce the risk of overtreatment without compromising oncologic outcome for patients with EC
    corecore