Ovarian Cancer

OVARIAN CANCER: Signs and Symptoms you should be aware

  • In 2017, there were an estimated 192,446 women living with ovary cancer in the United States.
  • Every 24 min a woman is diagnosed with ovarian cancer in United States
  • 1 in 74 women will develop ovarian cancer in her life time
  • 2017 will have approximately 22,240 new cases and 14,080deaths from ovarian cancer

Ovarian cancer remains the most deadly gynecologic malignancy in the United States. The
high mortality associated with ovarian cancer is due largely to the inability to detect the disease
early and the lack of effective therapeutics for women with recurrent disease.

Most patients with ovarian cancer are asymptomatic, with the cancer being discovered incidentally during ultrasonography or routine pelvic examination. Some cancer, however, may be associated with a range of symptoms, sometimes severe, including the following :

  • Pain or discomfort in the lower abdomen
  • Severe pain from torsion (twisting) or rupture – Cystic cancer rupture is characterized by sudden, sharp, unilateral pelvic pain; this can be associated with trauma, exercise, or coitus. Discomfort with intercourse, particularly deep penetration
  • Difficulty having bowel movements
  • Desire to defecate – This can occur if pressure develops
  • Urinary frequency. This can occur frequently, due to pressure on the bladder
  • Irregularity of the menstrual cycle and abnormal vaginal bleeding
  • Abdominal fullness and bloating
  • Indigestion, heartburn, or early satiety
  • painful and heavy periods
  • Dull, bilateral pelvic pain
  • Tachycardia and hypotension
  • Adnexal or cervical motion tenderness
  • Diffusely tender abdomen with rebound tenderness and guarding
  • Weight loss, enlarged lymph nodes in the neck, shortness of breath, and signs of pleural effusion – These may be associated with advanced malignant disease

What are the treatments for Ovarian Cancers?

 

In the United States, the overall ovarian cancer 5-year survival rate is 46.2%, resulting in more than 14,000 deaths annually.  The poor prognosis associated with this malignancy is largely attributable to the fact that almost 75% of women have stage III or stage IV disease at the time of diagnosis.  Ovarian cancer is usually associated with vague, nonspecific symptoms as it progresses, which contributes to delayed diagnosis and increased mortality.
Multiple studies have examined pelvic ultrasonography and tumor markers, such as CA 125, as possible screening tools to increase early detection in asymptomatic women. However, neither modality alone or in combination has sufficient sensitiv ity or specificity to recommend it for use in the general population. Nevertheless, the search for an appropriate screening tool continue.

New clinical practice guideline
advises neoadjuvant chemotherapy
for certain women with ovarian cancer

Ovarian cancer remains the most deadly gynecologic malignancy in the United States. What are the practice implications of recent research results on screening, neoadjuvant chemotherapy, and an investigational agent that targets recurrent ovarian cancer?

Neoadjuvant chemotherapy, in which chemotherapy is administered prior to surgical cytoreduction, challenges the traditional treatment paradigm for advanced stage ovarian cancer. Several randomized controlled trials have reported equivalent survival for primary surgical cytoreduction and NACT. Importantly, women who received NACT had fewer complications and were more likely to have optimal cytoreduction at the time of surgery. These
studies have limitations, however, and the role of NACT remains uncertain. To help guide clinicians, the Society of
Gynecologic Oncology and the American Society of Clinical Oncology convened an expert panel to provide  recommendations and guidance on the evaluation of women for and the use of NACT in the setting of
advanced ovarian cancer.

Strong clinical evidence supports thatall women with suspected stage IIIC or stage IV ovarian cancer should be evaluated by a gynecologic oncologist prior to the initiation of therapy. The evaluation should include at least a computed tomography scan of the chest, abdomen, and pelvis to assess the extent of disease and resectability.
A preoperative risk assessment should be performed to assess risk factors for increased morbidity and mortality.
Women who have a high perioperative risk profile or a low likelihood of achieving surgical reducition  to 1 cm or less of residual tumor should receive NACT. Prior to the initiation of NACT, histologic confirmation of ovarian cancer should be obtained.

For women diagnosed with ovarian cancer, treatment paradigms for the initial management of the disease have shifted dramatically. Based on data from multiple randomized controlled trials, neoadjuvant chemotherapy (NACT) is being used more frequently. The American Society of Clini-ncal Oncology and the Society of Gynecologic Oncology developed consensus recommendations for the appropriate use of NACT and primary cytoreductive surgery for women with ovarian cancer.

Patients who are appropriate candidates for NACT should be treated with a platinum and taxane doublet and should
receive interval cytoreduction following 3 to 4 cycles of therapy if a favorable response is noted. Patients whose disease progresses despite NACT have a poor prognosis, and there is little role for surgical treatment with
the exception of palliative purposes.

Approximately 85% of women with ovarian cancer will develop recurrent disease. Women with ovarian cancer
are commonly treated with a range of antineoplastic agents over the course of their lifetime. As such, there is a great need for additional active therapeutic agents in this setting. Recently, substantial effort has been directed toward “precision” or “personalized medicine” in oncology.

Precision medicine, targeted therapies in oncology Precision medicine refers to the customization of medical therapy based on the genetic characterization of the individual patient or the molecular profile of the patient’s tumor.
As a result of large-scale molecular profiling from projects such as the International Cancer Genome Consortium and The Cancer Genome Atlas, an abundance of molecular data has been generated through the characterization of multiple tumor types. This has led to the discovery of key cancer drivers, alterations, and specific molecular

profiles that have distinct prognostic and treatment implications. These data, in combination with the commercial availability of molecular profiling tests, has made precision medicine a reality for women with ovarian cancer.
This wealth of new information has led to development of targeted therapeutics that block the growth and spread of cancer by acting on specific molecules or molecular pathways.  Targeted therapies approved for cancer treatment include hormonal therapies, signal transduction inhibitors, gene expression modulators, apoptosis inducers, angiogenesis inhibitors, and immunotherapies

Finally, all of oncology has moved toward incorporating molecularly targeted therapeutics directed toward individual genetic abnormalities in tumors, so-called precision medicine. In ovarian cancer, poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) has emerged as an important tar- get, particularly for women with BRCA gene pathway mutations. We describe a recently published randomized controlled trial of the PARP inhibitor Niraparib.

How PARP inhibitors work

PARP inhibitors are a class of agents that are emerging as important therapies for ovarian cancer. These agents block the nuclear protein PARP, which functions to detect and repair single-strand DNA breaks with the resulting accumulation of double-stranded DNA breaks.15 In the setting of DNA damage, the homologous recombination repair pathway is activated for repair. However, homologous recombination deficiencies (HRD) can arise as a result of BRCA1 or BRCA2 mutations or BRCA-independent pathways, which effectively disable this DNA repair pathway.
As a result, when PARP inhibitors are used in patients with HRD, the cell cannot repair double-stranded DNA breaks and this leads to “synthetic lethality.” Understanding this molecular mechanism of PARP inhibitors as well as the frequent abnormalities in the BRCA genes and HRD pathways in ovarian cancer has provided an important potential therapeutic target in ovarian cancer. A number of PARP inhibitors are now commercially available
and are undergoing testing in ovarian cancer.

Niraparib for ovarian cancer: In a randomized, double-blind, phase 3 tria by Mizra and colleagues, 553 women with platinum-sensitive recurrent ovarian cancer who responded to therapy were divided according to the presence or absence of a germline BRCA (gBRCA) mutation and randomly assigned to niraparib 300 mg or placebo once daily. Women in the niraparib group had a significantly longer median duration of progression-free survival than
did those in the placebo group. This was most pronounced in women in the gBRCA cohort (21.0 vs 5.5 months). Importantly, niraparib was associated with improved progression-free survival in HRD-positive patients without gBRCA mutations (12.9 vs 3.8 months) as well as in the HRD-negative subgroup (6.9 vs 3.8 months). Overall, niraparib was well tolerated. About 15% of women discontinued the drug due to toxicity. Significant (grade 3 or 4)
adverse events were seen in three-quarters of women treated with niraparib, and they most commonly consisted of hematologic toxicities. Patient-reported outcomes were similar for both groups, indicating no significant effect from niraparib on quality of life.

This study’s results suggest that niraparib has clinical activity against ovarian cancer. Importantly, niraparib was active in women with gBRCA mutations, in those with HRD without a gBRCA mutation, and potentially in women without HRD. If approved by the US Food and Drug Administration, niraparib will join olaparib and rucaparib as
a newly approved therapeutic agent for ovarian cancer. This study provides important evidence that suggests niraparib maintenance therapy may be an efficacious and important addition to the treatment armamentarium for platinum-sensitive ovarian cancer.

 

The information in this document does not replace a medical consultation. It is for personal guidance use only. We recommend that patients ask their doctors about what tests or types of treatments are needed for their type and stage of the disease.

Sources:

  • American Cancer Society
  • The National Cancer Institute
  • National Comprehensive Cancer Network
  • American Academy of Gastroenterology
  • National Institute of Health
  • MD Anderson Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • American Academy of Hematology

 

 

 

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