Objective: To compare oncologic and perioperative outcomes in patients who underwent minimally invasive surgery (MIS) compared to laparotomy for newly diagnosed early-stage cervical carcinoma. Methods:We retrospectively identified patients who underwent radical hysterectomy for stage IA1 with lymphovascular invasion (LVI), IA2, or IB1 cervical carcinoma at our institution from 1/2007-12/2017. Clinicopathologic characteristics and surgical and oncologic survival outcomes were compared using appropriate statistical testing. Multivariable Cox regression analysis was used to control for potential confounders. Results: We identified 196 evaluable cases-117 MIS (106 robotic [90.6%]) and 79 laparotomy cases. Cohorts had similar age, BMI, substage, histologic subtype, clinical and pathologic tumor
In metastatic cancer, the role of heterogeneity at the tumor-immune microenvironment, its molecular underpinnings and clinical relevance remain largely unexplored. To understand tumor-immune dynamics at baseline and upon chemotherapy treatment, we performed unbiased pathway and cell type-specific immunogenomics analysis of treatment-naive (38 5 samples from 8 patients) and paired chemotherapy treated (80 paired samples from 40 patients) high-grade serous ovarian cancer (HGSOC) samples. Whole transcriptome analysis and imagebased quantification of T cells from treatment-naive tumors revealed ubiquitous variability in immune signaling and distinct immune microenvironments co-existing within the same individuals and within tumor deposits at diagnosis. To systematically explore cell type 10 composition of the tumor microenvironment using bulk mRNA, we derived consensus immune and stromal cell gene signatures by intersecting state-of-the-art deconvolution methods, providing improved accuracy and sensitivity when compared to HGSOC immunostaining and leukocyte methylation data sets. Cell-type deconvolution and pathway analyses revealed that Myc and Wnt signaling associate with immune cell exclusion in untreated HGSOC. To evaluate 15 the effect of chemotherapy on the intrinsic tumor-immune heterogeneity, we compared sitematched and site-unmatched tumors before and after neoadjuvant chemotherapy.Transcriptomic and T-cell receptor sequencing analyses showed that site-matched samples had increased cytotoxic immune activation and oligoclonal expansion of T cells after chemotherapy, which was not seen in site-unmatched samples where heterogeneity could not be accounted 20for. These results demonstrate that the tumor-immune interface in advanced HGSOC is intrinsically heterogeneous, and thus requires site-specific analysis to reliably unmask the impact of therapy on the tumor-immune microenvironment. 1050 Conceptualization [Ideas; formulation or evolution of overarching research goals and aims] AS, AJS, MLM, ES Data curation [Management activities to annotate (produce metadata), scrub data and maintain research data (including software code, where necessary for interpreting the data itself) for 1055 initial use and later re-use] AJS, KL, PC Formal analysis [Application of statistical, mathematical, computational, or other formal techniques to analyse or synthesize study data] 1060 AJS Funding acquisition [Acquisition of the financial support for the project leading to this publication] AV, ES, AS, MLM 1065 Investigation [Conducting a research and investigation process, specifically performing the experiments, or data/evidence collection] PC, KL, TW, YM, IN, BW, DC, ES 1070 50 Methodology [Development or design of methodology; creation of models] ES Project administration [Management and coordination responsibility for the research activity planning and execution] 1075 AS, MLM, ES Resources [Provision of study materials, reagents, materials, patients, laboratory samples, animals, instrumentation, computing resources, or other a...
For patients with ID and IL cancers, the overall sensitivity of FS is >50%, but the yield of FS is <10% for individuals > or =60 years of age with T1a/b tumors. Intraoperative FS may not be worthwhile for this low-yield subset, especially for patients with invasive breast cancer of favorable type.
A prophylactic, extended carboplatin infusion was not associated with a decreased HSR rate. The overall low HSR rate suggests that premedication may help reduce HSRs.
PURPOSE: CA125 is widely used for the diagnosis and monitoring of women with epithelial ovarian cancer. However, CA125 will not be elevated in ~20% of patients. Human epididymis protein 4 (HE4) was approved by the FDA in 2008 to monitor ovarian cancer. The objective of this study was to evaluate whether HE4 would serve as a useful biomarker in patients with a normal CA125 at either the time of diagnosis or at the time of recurrence. METHODS: Twenty–one patients with high–grade serous ovarian cancer and CA125 values <50U/ml at the time of diagnosis were identified from a bank of serum specimens collected between 2006–2012. Twenty patients with high–grade serous ovarian cancer and CA125 values >1000U/ml served as positive controls and 11 patients without disease served as negative controls. Fourteen patients with an elevated CA125 at diagnosis (>50 U/ml) and a normal CA125 at the time of recurrence were also identified. HE4 was measured using the Abbott Architect i2000 assay and validation was performed using the Fujirebio HE4 ELISA assay. Normal age–based HE4 values were obtained from the published literature (Urban N, et al.; PMID: 22962406). Data was compared between groups using standard two–sided statistical tests. RESULTS: At the time of diagnosis, the mean HE4 was 1082±437.9 in the positive control patients with elevated CA125, the mean HE4 was 50.96±11.43 in the patients without disease, and 214.4±236.9 in patients with a normal CA–125 (P = <.0001 compared to normal controls; Student's t–test). At the time of recurrence, the mean HE4 was 102.7±83.29 in patients with normal CA125 levels. For 12 of 14 (86%) patients, the HE4 value was greater than the expected normal age–based reference. CONCLUSIONS: These preliminary data suggest that HE4 values are elevated in newly diagnosed ovarian cancer patients with a normal CA125 value. HE4 also appears to be a potentially useful biomarker for detecting recurrent disease in patients with an elevated CA125 at the time of diagnosis who have a normal CA125 level at the time of recurrence. Citation Format: Katherine LaVigne, MD, Fanny Dao, MS, Nadeem Abu–Rustum, MD, Petar Jelinic, PhD, Lakshmi V. Ramanathan, PhD, Martin Fleisher, PhD, Douglas A. Levine, MD. HE4 IS A BIOMARKER FOR NEWLY DIAGNOSED AND RECURRENT HIGH–GRADE SEROUS OVARIAN CANCERS WITH NORMAL CA–125 VALUES [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP01.
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