Controversies Continue in NCCN Ovarian Cancer Guidelines

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National Comprehensive Cancer Network (NCCN) 17th Annual Conference

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Controversies Continue in NCCN Ovarian Cancer Guidelines

Neoadjuvant Chemotherapy and CA-125 Reviewed

March 20, 2012 (Hollywood, Florida) — The ovarian cancer guidelines from the National Comprehensive Cancer Network (NCCN) address a number of ongoing controversies, according to a presenter here at the NCCN 17th Annual Conference.

 

"There have not been a lot of changes in the past year, but there are various areas of controversy in the guidelines," Robert Morgan, MD, from the City of Hope Comprehensive Cancer Center in Los Angeles, California, told Medscape Medical News at the conference.
One such controversy is about the usefulness of the biomarker CA-125 to monitor patients who have been treated with surgery and/or chemotherapy. Dr. Morgan called CA-125 the "most controversial" aspect of patient follow-up.......

abstract: Minireview: Human Ovarian Cancer: Biology, Current Management, and Paths to Personalizing Therapy. March 13th

Minireview: Human Ovarian Cancer: Biology, Current Management, and Paths to Personalizing Therapy  [Endocrinology. 2012] - PubMed - NCBI

Endocrinology. 2012 Mar 13. [Epub ahead of print]

Minireview: Human Ovarian Cancer: Biology, Current Management, and Paths to Personalizing Therapy.

Abstract

More than 90% of ovarian cancers have been thought to arise from epithelial cells that cover the ovarian surface or, more frequently, line subserosal cysts. Recent studies suggest that histologically similar cancers can arise from the fimbriae of Fallopian tubes and from deposits of endometriosis. Different histotypes are observed that resemble epithelial cells from the normal Fallopian tube (serous), endometrium (endometrioid), cervical glands (mucinous), and vaginal rests (clear cell) and that share expression of relevant HOX genes which drive normal gynecological differentiation. Two groups of epithelial ovarian cancers have been distinguished: type I low-grade cancers that present in early stage, grow slowly, and resist conventional chemotherapy but may respond to hormonal manipulation; and type II high-grade cancers that are generally diagnosed in advanced stage and grow aggressively but respond to chemotherapy. Type I cancers have wild-type p53 and BRCA1/2, but have frequent mutations of Ras and Raf as well as expression of IGFR and activation of the phosphatidylinositol-3-kinase (PI3K) pathway. Virtually all type II cancers have mutations of p53, and almost half have mutation or dysfunction of BRCA1/2, but other mutations are rare, and oncogenesis appears to be driven by amplification of several growth-regulatory genes that activate the Ras/MAPK and PI3K pathways. Cytoreductive surgery and combination chemotherapy with platinum compounds and taxanes have improved 5-yr survival, but less than 40% of all stages can be cured. Novel therapies are being developed that target high-grade serous cancer cells with PI3Kness or BRCAness as well as the tumor vasculature. Both in silico and animal models are needed that more closely resemble type I and type II cancers to facilitate the identification of novel targets and to predict response to combinations of new agents.

(very short) abstract: A Surveillance Conundrum: A Case of 4 Distinct Primary Malignancies in a BRCA-1 Mutation Carrier - Intl Jnl Gyn Pathology

Abstract

Women with HBOC syndrome present a unique challenge to the oncology community, as will many genetic cancer syndromes yet to be discovered as genetic testing increases in availability. Issues of management and, most importantly, implication are yet to be elucidated. After a diagnosis of epithelial ovarian carcinoma lifelong follow-up is recommended. Given the high recurrence rate and dismal long term prognosis of advanced epithelial ovarian carcinoma this recommendation is more often than not moot. There are no clear guidelines or recommendations for surveillance designed for women with disease free survival greater than five years. This case presents a unique scenario of a woman with predictable disease that remains unpreventable.