Interval debulking surgery for advanced epithelial ovarian cancer
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Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on survival of debulking surgery.
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Ovarian cancer is the leading cause of morbidity/mortality from gynecologic malignancy.Early detection of disease is difficult due to the propensity for ovarian cancer to disseminate throughout the peritoneum.Currently, there is no single accurate test to detect primary or recurrent ovarian cancer.We report a novel clinical strategy using PPF: a multimodal, PET and optical, folate receptor (FR)-targeted agent for ovarian cancer imaging.The capabilities of PPF were evaluated in primary human ovarian cancer cells, in vivo xenografts derived from primary cells and ex vivo patient omemtum, as the heterogeneity and phenotype displayed by patients is retained.Primary cells uptake PPF in a FR-dependent manner demonstrating approximately a 5-to 25-fold increase in fluorescence.By both PET and fluorescence imaging, PPF specifically delineated FR-positive, ovarian cancer xenografts, with similar tumor-to-background ratios of 8.91±0.91 and 7.94±3.94,and micro-metastatic studding (<1mm), which demonstrated a 3.5-fold increase in PPF uptake over adjacent normal tissue.Ex vivo patient omentum demonstrated selective uptake of PFF by tumor deposits.The ability of PPF to identify metastatic deposits <1mm could facilitate more complete debulking (currently, optimal debulking is <10mm residual tumor), by providing a more sensitive imaging strategy improving treatment planning, response assessment and residual/recurrent disease detection.Therefore, PPF is a novel clinical imaging strategy that could substantially improve the prognosis of patients with ovarian cancer by allowing pre-, post-and intra-operative tumor monitoring, detection and possibly treatment throughout all stages of therapy and tumor progression.
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Abstract Survival of ovarian cancer patients is directly related to the amount of residual disease present after debulking surgery. In 80% of the cases, extensive microscopic cancer remains even after the patient is deemed optimally debulked. Hence, detection of sub-mm cancer clusters during tumor excision is a critical unmet need. Recent studies have shown that reducing the dimensions of residual cancer to less than 1 mm significantly improves clinical outcomes. In the present study we evaluate the performance of a fluorescent, molecular imaging agent, LUM015 (Lumicell, Wellesley, MA), which is activated by cathepsin enzymes in the tumor, and a wide-field-of-view imaging device (Lumicell) to detect sub-mm residual cancer clusters in an mouse model for ovarian cancer. In this study, we generated orthotopic ovarian cancer mouse models(n=10) with well characterized serous ovarian cancer cell lines, CP70 and SKOV3. Once the tumor disseminated, the imaging agent LUM015 (3.52 mg/kg) was injected via the tail vein, and after 6 hours, the mice were euthanized. Tumor debulking was performed throughout the abdominal cavity. After debulking, the whole abdominal wall was dissected in 4 quadrants, organs were harvested and all were imaged with the LUM device. Features exhibiting high fluorescence were marked and dissected, prepared into slides, and stained with hematoxylin and eosin for pathologic correlation with LUM015 fluorescence imaging. In 36 tissues from orthotopic ovarian cancer mouse models, LUM015 imaging system could detect the tumor presence with 100% of sensitivity and 60% of specificity. We demonstrated that the imaging system can detect sub-mm cancer clusters that could not be identified with visual inspection. With a cathepsin activated fluorescence imaging molecule (LUM015) and a wide-field-of-view imaging device, we detected microscopic residual ovarian cancer tumors in orthotopic xenograft models after debulking grossly with high sensitivity. Translation of this imaging technology into the clinical setting may help to detect microscopic residual tumor features during the debulking operation in ovarian cancer. Citation Format: Youngjeong Na, Tim Kwok, Christopher Awtrey, David B. Strasfeld, Jorge M. Ferrer, David Lee, Michael J. Birrer. Identification of microscopic ovarian tumor foci utilizing a novel imaging device in a murine ovarian cancer model, an opportunity to improve optimal cytoreduction. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2056. doi:10.1158/1538-7445.AM2014-2056
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Ovarian tumor
Minimal Residual Disease
Abdominal cavity
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Epithelial ovarian cancer is a highly curable disease when diagnosed in an early stage. Unfortunately, treatment for advanced stage disease is mainly palliative. This article will review new developments in the diagnosis of ovarian cancer involving diagnostic imaging techniques and circulating tumor markers. It will discuss the current role of surgery in the treatment of the disease, including cytoreductive surgery, interval debulking surgery and surgery following neoadjuvant chemotherapy. It will evaluate the currently available chemotherapy treatments for epithelial ovarian cancers and present new developments in the medical management of this disease.
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[This corrects the article DOI: 10.2147/CMAR.S313013.].
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Adjuvant Chemotherapy
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