Ovarian Cancer

Background

EarlyStages keyOvarian Cancer is the second most common gynecologic malignancy and the most lethal of all gynecological malignancies in the US. Each year, there are approximately 22,000 new cases with 14,000 cancer-related deaths in the US, making it the 5th leading cause of cancer death in women.

The peak incidence is near age 60; however, the age at diagnosis is often younger in women with a hereditary ovarian cancer syndrome. Known risk factors include increasing age, nulliparity, endometriosis, obesity, and hormone replacement therapy. Several genetic conditions also increase the chance of developing ovarian cancer, notably mutations in the BRCA1 or BRCA2 DNA repair genes. Factors that are associated with a reduced risk include: previous pregnancy, history of breastfeeding, oral contraceptives, and tubal ligation.

Ovarian cancer is most often diagnosed at an advanced stage as tumors tend to be painless coupled with the fact that there is no clear early detection or screening test. Symptoms are mainly related to mass-effect or are associated with metastatic disease. Earlier symptoms such as pelvic discomfort, bloating and, bladder/bowel changes are often dismissed, and women most commonly present with some combination of heartburn, nausea, early satiety, constipation, and abdominal pain. The majority of women present when their tumors have already spread from the primary site and invaded the peritoneal cavity. At this stage, women have a poor prognosis with only a 32% 5-year survival rate.

Current Treatment

Treatment of ovarian cancer usually involves surgical staging and cytoreduction (debulking) followed by chemotherapy. Surgery alone may be sufficient for low-grade tumors confined to the ovary. Chemotherapy is often added for patients with more aggressive tumors or when advanced disease is present.

Focused Ultrasound Research

The treatment and subsequent prognosis of ovarian tumors relies heavily on the tumor’s response to chemotherapy. Tumor tissue is relatively ischemic, particularly in the center of larger masses; however, by creating a state of local hyperthermia, blood flow can be increased to the tumor—thus enhancing local delivery of chemotherapy via the blood stream. This process of inducing hyperthermia in a tumor is known as sensitization and has already been proven effective in the clinical setting. Through this mechanism, physicians can enhance the effects of chemotherapy or achieve the same therapeutic outcome with lower doses of chemotherapy, thereby minimizing the adverse effects. More specifically, studies have already demonstrated that hyperthermia sensitizes human ovarian cancer cells to cisplastin (a commonly used chemotherapeutic agent) by increasing cellular and DNA platinum accumulation.

Focused ultrasound provides a radiation free, non-invasive method of inducing local hyperthermia. FUS is an optimal approach for inducing hyperthermia because the ultrasonic beam can be conformed to a wide variety of shapes and sizes. Furthermore, tissue temperature can be monitored real-time using magnetic resonance imaging, making FUS an excellent complement to drug therapy.

An addition to the hyperthermic effect of focused ultrasound is the potential benefit of sonodynamic therapy. In preclinical work on a nude mice model of ovarian cancer, sonification of the combination of HMME (hematoporphyrin monomethyl ether) and PLGA (polylactic-co-glycolic acid) microcapsules, resulted in significant decrease in tumor survival.

Although the above reports are encouraging, there is considerable additional work that must be done before this research becomes available for clinical use.

Notable Papers

Yan S, Lu M, Ding X, Chen F, He X, Xu C, Zhou H, Wang Q, Hao L, Zou J. HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy. Sci Rep. 2016 Aug 18;6:31833. doi: 10.1038/srep31833.

C. S. Muenyi, A. R. Pinhas, T. W. Fan, G. N. Brock, C. W. Helm, and J. C. States, “Sodium arsenite ± hyperthermia sensitizes p53-expressing human ovarian cancer cells to cisplatin by modulating platinum-DNA damage responses.,” Toxicol. Sci. : Off. J. Soc. Toxicol., vol. 127, no. 1, pp. 139–149, May 2012.

S. Wang, V. Frenkel, and V. Zderic, “Optimization of pulsed focused ultrasound exposures for hyperthermia applications.,” J. Acoust. Soc. Am., vol. 130, no. 1, pp. 599–609, Jul. 2011.

S. Wang, V. Zderic, and V. Frenkel, “Extracorporeal, low-energy focused ultrasound for noninvasive and nondestructive targeted hyperthermia.,” Future Oncol., vol. 6, no. 9, pp. 1497–1511, Sep. 2010.

H. Matsumoto, “[Revisiting sensitization mechanisms in cancer thermochemotherapy].,” Fukuoka igaku zasshi = Hukuoka Acta medica, vol. 100, no. 4, pp. 95–103, Apr. 2009.

     

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