Ovarian Cancer: The Forgotten Killer
In high-income countries, cancer remains the commonest cause of disease-related death in adolescent and young adults despite survival improvements. With more than one million new diagnoses of cancer in adolescents and young adults annually worldwide, and their number of life-years affected by cancer being greatest of all ages, the global burden of cancer in adolescents and young adults exceeds all other ages. In low- and middle-income countries, where the great majority of the worlds adolescents and young adults reside the needs of those with cancer have been identified and demand attention. Unique to this age group, the psychosocial challenges they face are the utmost across life's spectrum (Brunet et al, 2018)
Epithelial ovarian cancer is the fifth most common cause of cancer death in females in the United Kingdom. It is the second most common genital malignancy after uterine cancer in women and accounts for the majority of deaths from gynecological malignancies in western countries. Latest data shows one in 43 women will develop epithelial ovarian cancer during their lifetime.
There is increasing clinical evidence in support of the fallopian tube epithelium as being the source of the origin of high grade serous ovarian cancer. This was derived from the detection of premalignant cells in the epithelial of fallopian tube known as serious tubal intraepithelial carcinomas. Despite the continuous advances in diagnostics and imaging, more than 70% of patient with newly diagnosed epithelial ovarian cancer will present with an advanced stage tumor. This is mainly attributed to the unusual tumor biology and clinical behavior of the disease.
Signs and symptoms usually reported occur at the later stage include abdominal bloating and distention with pain, urinary frequency, postmenopausal bleeding, loss of appetite and occasionally rectal bleeding. The last decades have brought advances in the treatment of epithelial ovarian cancer but the survival rate of women with it has changed little since the use of platinum-based treatments were introduced 30 years ago.
Currently, the approach doctors’ use for advanced growth is to debulk the tumor and give intravenous chemotherapy as it is felt after removing most of the tumor, the epithelial ovarian cancer is more receptive to effects of the chemotherapy. Nevertheless, despite the maximum effort, patients outcomes vary broadly. So far there are no valid biomarkers established preoperative that can reliably predict a surgical and clinical outcome. Because of this, the surgical approach can’t be individualized. Even with a total macroscopic tumor removal, 20% of patients will relapse within the first 12 months after surgery.
There has never been a more fruitful time for surgical advances then now. Implementation of highly modern and revolutionary bioengineering technology into daily surgical techniques have optimized surgery and reduced morbidity. From bench to bedside this is a prime time for many techniques to be validated and established within randomized clinical trials and become an integral part of the surgical management of this challenging disease (Cunnea et al, 2018).
Epithelial ovarian cancer is the second most common gynecological cancer and in 2012m was accountable for the deaths of 157,917 women worldwide. As epithelial ovarian cancer causes few symptoms in its early stages in approximately 75% of the patients’ disease has spread throughout the peritoneal cavity at the time of diagnosis. Therapeutic success is dependent on two essential parts of treatment: achievement of optimal cytoreductive surgery and response to adjuvant (something, that helps the effectiveness of medical treatment) chemotherapy.
Over the past decades the combination of platinum and taxan based regimen has provided best response rates. Even with cytoreductive surgery after six cycles of chemotherapy did not show any improvement in survival so far. Age at diagnosis, tumor stage and the amount of residual disease after cytoreductive surgery are widely recognized as prognostic parameters influencing survival. In epithelial ovarian cancer data on the association between duration of chemotherapy and survival outcome are partially inconsistent. This study found however the duration of adjuvant chemotherapy on the course of epithelial ovarian cancer has not been sufficiently investigated.
When the survival rate was looked at according to the amount of delay of total chemotherapy duration was associated with shorter periods free of cancer. This study evaluated the impact of the duration of an adjuvant intravenous chemotherapy on the prognosis of patients with epithelial ovarian cancer. The data showed an association between a prolonged duration of chemotherapy and a shortened progression free cancer specific and overall survival.
A delay of chemotherapy greater than nine days is associated with a significantly higher risk of progression; of dying from epithelial ovarian cancer. Moreover even a short-term delay seems to negatively affect progression free time. The study also found in those patients who had no delay of chemotherapy at two years progression free survival was 79.6%. Interestingly, not even one third of the patients received adjuvant chemotherapy in the optimal time frame. They also feel that larger studies are needed to validate the results they achieved (Seebacher et al, 2017).
Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. Ovarian cancer has the highest mortality of all gynecologic cancers in the world. The majority of patients find out they have the disease after it has already spread beyond the ovaries to the peritoneal surface. The most effective treatment for this advanced disease involves a maximum effort to reduce the tumor burden through surgery followed by six cycles of intravenous chemotherapy with carboplatin and paclitaxel.
Intraperitoneal delivery of chemotherapy enhances drug delivery at the peritoneal surface and may improve outcomes by eliminating resi8dual microscopic peritoneal disease more efficiently than intravenous administration of chemotherapy.
Combination treatment with intravenous and Intraperitoneal chemotherapy has been shown to prolong overall survival after primary surgery among patient with stage three ovarian cancer. Catheter-related issues, increased demands on patient, and gastrointestinal and kidney side effects have hampered the adoption of this approach in most countries. Intraperitoneal chemotherapy during surgery can be delivered under hyperthermic conditions. The hyperthermia helps to increase the penetration of the chemotherapy at the peritoneal surface and increase the sensitivity of the cancer to the chemotherapy by improving the DNA repair.
After standard treatment for ovarian cancer, the peritoneal surface is the primary site of disease recurrence. Previous trials that compared six cycles of intraperitoneal chemotherapy plus intravenous chemotherapy and intravenous chemotherapy alone, showed that survival was 16 months longer after exposure to intravenous chemotherapy alone. Their results are promising and indicate that among women with advanced ovarian cancer, hyperthermic chemotherapy given Intraperitoneal during surgery resulted in longer survival rates (van Driel et al, 2018).
Women with ovarian cancer often undergo chemotherapy involving multiple agents. However little is known about treatment-related central neurotoxicity in this population. The goal of the study was to assess brain structure and function and neurocognitive abilities in patients with ovarian cancer following first-line chemotherapy. Eighteen patients with ovarian, peritoneal, and/or fallopian tube cancer and 18 healthy controls were followed and evaluated one to four months after completion of first-line taxane/platinum chemotherapy.
All participants underwent structural and functional MRI imaging and completed a battery of neuropsychological tests. These tests checked attention, memory, and exeutive functioning. They also underwent neuroimaging assessments to check on grey matter volume in the brain. The results showed that patients had significantly reduced grey matter volume compared to healthy controls.
They were however, no significant differences between the two groups on the neuropsychological tests. This was the first study to show structural and functional alterations involving the frontal and parietal regions of the brain in patients with ovarian cancer treated with first-line chemotherapy. These findings are consistent with studies involving women with breast cancer and provide additional supporting evidence for central neurotoxicity associated with taxane/platinum chemotherapy (Correa et al, 2017).
Brunet, J. et al. (2018). A scoping review of studies exploring physical activity among adolescents and young adults diagnosed with cancer. Psycho-Oncology,27(8). Wiley Online Library-abstract.
Correa, D.D. et al. (2017). Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: A pilot study. Brain Imaging and Behavior,11(6).
Cunnea, P. et al. (2018). Review of article: Novel technologies in the treatment and monitoring of advanced and relapse epithelial ovarian cancer. Convergent Science Physical Oncology, 3(1).
Parsonage, R.K. et al. (2017). Patient perspectives on delays in diagnosis and treatment of cancer: A qualitative analysis of free-text data. British Journal of General Practice.
Seebacher, V. et al. (2017). The impact of the duration of adjuvant chemotherapy on survival in patients with epithelial ovarian cancer-A retrospective study. PLoS ONE,12(1).
Van Driel, W.J. et al. (2018). Hyperthermic intraperitoneal chemotherapy in ovarian cancer. New England Journal of Medicine,378(3).