Natural History Of Ovarian Cancer Research Articles

Quality of Life of Patients with Advanced Stage Ovarian Cancer from Sanglah Hospital Denpasar: Serial Case Report

Background: Ovarian cancer is one of the malignancies in women, although it is not contagious, the cases continue to increase. Most ovarian cancers are diagnosed at an advanced stage (stage IIIC or IV). Patients with ovarian cancer can reduce their quality of life, especially at an advanced stage. The quality of life of patients is not only part of the natural history of ovarian cancer, but is also related to the therapy they receive. Especially the administration of chemotherapy or cytostatic drugs. Methods: This is a report of two cases of the advanced stage of ovarian cancer which were treated in the gynecological oncology room at Sanglah Hospital, Denpasar. The decrease in quality of life in patients with ovarian cancer is illustrated in the case. Results and Discussion: In the first case, a woman, aged 20 years, complained of abdominal pain and difficulty eating with a history of ovarian cancer. Patients diagnosed with axis 3 with Ovarian Ca post SOD, multiple nodules in the right lung due to metastases, post taping ascites, anemia, and hypoalbuminemia. Patients also experience hypovolemic shock, melena, etc. suspension. SRMD dd/ erosive gastritis. In the second case, a female patient, aged 32 years, was admitted on the 7th day due to abdominal pain, difficulty urinating with a history of ovarian cancer. Patients diagnosed with axis 3 with Ca Ovarian advanced stage, post-SOS, suspected metastases to the left pelvic sidewall, urinary retention after open cystostomy, mild anemia, pain-related neoplasms. Both patients conducted an assessment of the quality of life using the EORTC QLQ-C30 questionnaire. The majority of patients answered the number 4 for each question, which means that the patient is very difficult to carry out basic activities and functions of life. Patients must also be assisted for all activities. Patients choose the number 1 for the quality of health and quality of life which means very bad in this 1 week. Summary: The quality of life of two cases of advanced-stage ovarian cancer treated in the gynecological oncology room at Sanglah Hospital, Denpasar was poor. It is associated with pain, difficulty performing activities, and basic life functions.

Eliminating tumor cell entrapment from the natural history of ovarian cancer, a narrative summary

Eliminating tumor cell entrapment from the natural history of ovarian cancer, a narrative summary

“Benefit” of Routine Ovarian Biopsy during Laparotomy for Diseases of the Female Reproductive Organs.

Background: Ovarian cancer is the most common cause of death among patients diagnosed with reproductive organ cancers in Poland. Despite the progress and continual improvements in diagnostic techniques and methods of cancer treatment, the epidemiology and natural history of ovarian cancer remain largely unchanged. Approximately three quarters of ovarian carcinoma cases are not detected or treated until the third or fourth stage of the disease. The current routine diagnostic procedures include ultrasound examination, biochemistry marker assessments and histopathological evaluations of ovarian tissue to confirm a diagnosis. The preoperative diagnosis of ovarian cancer remains unsatisfactory, and the search for new effective methods has not provided satisfactory results.Objectives: To determine whether routine biopsy of macroscopically unchanged ovaries provides sufficient benefit.Material and methods: We conducted a clinical trial involving approximately 1,000 ovaries from which tissue samples were collected during reproductive organ surgeries, and the tissues were examined by a pathologist. Spearman’s rank correlation was used to compare the results statistically.Results: The results of the histopathological evaluation of macroscopically unchanged ovaries were normal in 99.8% of patients.Conclusion: In this context, routine biopsy of macroscopically unchanged ovaries does not provide sufficient benefit. Moreover, it may be associated with increases in surgical complications such as bleeding from the biopsy site. Therefore, biopsy of the ovaries during surgery of reproductive organs should not be performed routinely unless cancer is suspected.

Book Review: Advances in Diagnosis and Management of Ovarian Cancer

2014 Ovarian cancer remains a feared disease as the non-specific symptoms result in delayed diagnosis and presentation with late-stage disease. Samir A Fargaly, the editor, Consultant Obstetrician and Gynecologist at Weill Cornell Medical College, New York, acknowledges in the preface that a woman’s lifetime risk of getting ovarian cancer is approximately 1 in 72. It is not a common cancer, ranking ninth in order of frequency, but it is the fifth commonest cause of cancer deaths in women. It is difficult for the specialist in active practice to appreciate just how many advances in the management of ovarian cancer have occurred over the last 10 years or so. This text book addresses improvements in approaches to screening, detection, surgical and nonsurgical management of the disease, which, as the editor acknowledges in his preface, have enhanced survival of women with ovarian cancer. There is still scope for further improvement and this book underlines some of the challenges. The recognition of the multidisciplinary approach to the treatment of this disease is implied rather than explicitly stated in this book. The international list of authors range from diagnostic physicians to surgical and nonsurgical oncologists as well psychologists. The breadth of subject matter is ambitious and the chapters are necessarily short. The concise chapters, relevant to the undergraduate and specialist alike, have been written by recognised experts who bring the wealth of their experience to the text. The chapters are well referenced with current literature. The absence of evidence, where relevant, is declared. The illustrations are clear and appropriate. For example, the chapters on Surface Epithelial Tumors of the Ovary and Pathology of Non-epithelial Malignancies of the Ovary have excellent microscopic photographs that clarify the pathology for the nonspecialist. The difficulty with making a diagnosis of ovarian cancer makes screening an attractive option. An ideal screening program would be inexpensive, convenient and reproducible, and would detect the disease in its precancerous state where treatment would prevent progression to cancer. None of the current screening trials for the prevention of ovarian cancer has managed to achieve this. The trials for ovarian cancer have explored combinations of tumor markers and ultrasound. The chapter on screening highlights all the important screening trials and their limitations, which include the low prevalence of the disease and deficiencies in our understanding of the early natural history of ovarian cancer. Advances in diagnosis and management of ovarian cancer

Role of mesenchymal cells in the natural history of ovarian cancer: a review.

BackgroundOvarian cancer is the deadliest gynaecologic malignancy. Despite progresses in chemotherapy and ultra-radical surgeries, this locally metastatic disease presents a high rate of local recurrence advocating for the role of a peritoneal niche. For several years, it was believed that tumor initiation, progression and metastasis were merely due to the changes in the neoplastic cell population and the adjacent non-neoplastic tissues were regarded as bystanders. The importance of the tumor microenvironment and its cellular component emerged from studies on the histopathological sequence of changes at the interface between putative tumor cells and the surrounding non-neoplastic tissues during carcinogenesis.MethodIn this review we aimed to describe the pro-tumoral crosstalk between ovarian cancer and mesenchymal stem cells. A PubMed search was performed for articles published pertaining to mesenchymal stem cells and specific to ovarian cancer.ResultsMesenchymal stem cells participate to an elaborate crosstalk through direct and paracrine interaction with ovarian cancer cells. They play a role at different stages of the disease: survival and peritoneal infiltration at early stage, proliferation in distant sites, chemoresistance and recurrence at later stage.ConclusionThe dialogue between ovarian and mesenchymal stem cells induces the constitution of a pro-tumoral mesencrine niche. Understanding the dynamics of such interaction in a clinical setting might propose new therapeutic strategies.

Natural history of ovarian cancer.

Ovarian cancer is a disease laden with paradigms, and it is a serious health problem. It is important to know its natural history, as it is multifactorial in origin, and also to understand its behaviour given its risk factors which can lead to death from metastasis in patients. It continues to be a challenge for oncologists. An analytical literature review was performed to update the latest concepts of its origin, evolution, risk factors, pre-clinical horizon, and its clinical manifestations; until the death of the patient.

Early Preinvasive Lesions in Ovarian Cancer

Faced with the catastrophic prognosis for ovarian cancer due to the fact that it is most often diagnosed late at the peritoneal carcinomatosis stage, screening and early detection could probably reduce the mortality rate. A better understanding of the molecular characteristics of the different ovarian cancer subtypes and their specific molecular signatures is indispensable prior to development of new screening strategies. We discuss here the early natural history of ovarian cancer and its origins.

Natural History of Ovarian Cancer

Ovary cancer is a fullness paradigms disease and serious health problem Is important knows it’s natural history, because has multi-factor origins, and understood it’s behavior since risk factors until patient’s dead, metastatic disease in patient is reality to challenger for oncology group. Ovarian cancer screening is today difficult theme; almost patients with disease had advanced ovarian cancer in the first visit with oncology. In this work we made a bibliographic report about natural history, is an analytic review that’s brings up concepts since etiology theirs risk factors, evolution sources, preclinical horizon, clinical disease and related symptoms, without treatments, until host dead.

Latest research and treatment of advanced-stage epithelial ovarian cancer.

The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics, despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free survival and overall survival, although the cure rates have been affected only modestly. Maintenance therapy holds promise, but studies have yet to identify an agent and/or strategy that can affect survival. Recurrent disease is largely an incurable state; however, current intervention with selected surgery, combination and targeted therapy and investigational protocols are impacting progression-free survival. Ovarian cancer is a diverse and genomically complex disease, which commands global attention. Rational investigation must balance the high rate of discovery with lagging clinical investigation and limited patient resources. Nevertheless, growth in our armamentarium offers unprecedented opportunities for patients suffering with this disease. This Review presents and reviews the contemporary management of the disease spectrum termed epithelial 'ovarian' cancer and describes the direction and early results of clinical investigation.

The UKCTOCS Experience—Reasons for Hope?

There has been concern about current ovarian cancer screening strategies after the publication showing a lack of benefit from screening in the ovarian part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The ongoing United Kingdom Collaborative Trial of Ovarian Cancer Screening involves 202,638 low-risk postmenopausal women. The performance characteristics on prevalence screen in sensitivity, specificity, and stage distribution have been encouraging. Screening differs from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial in the use of algorithms to interpret CA125 and ultrasound imaging and well-defined, centrally coordinated management of screen-detected abnormalities with protocols for intervention based on screening findings. There is a possibility that these essential differences may be sufficient to alter the natural history of ovarian cancer and ultimately lead to demonstration of a mortality benefit from screening when the trial reports in 2014/2015.

Epithelial Ovarian Cancer: Focus on Targeted Therapy

Over the past five decades ovarian cancer has been of considerable interest to clinical cancer investigators due to the fact that it is among the most chemosensitive of all solid tumors [1]. Unfortunately, despite the advances in the chemotherapeutic management of this malignancy, the large majority of patients ultimately recur, progress, and ultimately die as a direct result of complications of the disease process. Thus, there is a critical need to find novel agents that may favorably impact the natural history of ovarian cancer. In recent years there has been a particular focus in the cancer research community to discover and subsequently develop clinically active drugs that are capable of specifically targeting biological pathways relevant in a particular tumor type (e.g., ovarian cancer) and even within a specific patient with that type of cancer (so-called, “personalized medicine”). Research in this arena in ovarian cancer remains in its early stages although a number of quite exciting developments have recently been reported in the peer-reviewed medical literature that suggest the realistic potential that this novel general class of drugs will soon become important components of “standard-of-care” in the management of this difficult malignancy. In this special issue, investigators from around the world have contributed to this literature by summarizing a number of important developments. In the papers of this special issue, an initial discussion of the role of surgical cytoreduction in the malignancy is followed by an overview of the management of recurrent ovarian cancer and the relevance of molecular abnormalities in specific ovarian cancer subtypes. This is followed by several excellent and comprehensive overviews of the possible roles of targeted therapy in ovarian cancer, the potential impact of antiangiogenic drugs, epidermal growth factor and PARP inhibitors, disruption of insulin and glucose pathways, and novel treatments affecting histone deacetylase and metastatic colonization, as well as an innovative approach to immunotherapy in the malignancy. The peer-reviewed papers in this special issue provide important insight into both the current and future management of epithelial ovarian cancer. M.Markman Jalid Sehouli Charles F. Levenback Dennis S. Chi

Place de la chimio-hyperthermie intrapéritonéale (CHIP) dans le cancer de l'ovaire

Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer. Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer. Literature review reveals a number of different experiences on feasibility of this technique, but scientific evidence of current studies remains poor. Much more research is still required to elucidate unanswered questions. Before this technique can be routinely used, some controversial aspects have to be defined: which drug is the best to deliver and at what temperature, is it necessary to use mono- or poly-chemotherapy regimens, which is the time-point for HIPEC in the natural history of ovarian cancer: at front-line therapy, at interval debulking following initial neo-adjuvant chemotherapy, at consolidation following front-line therapy, or at the time of recurrence. Nevertheless, we must not forget that the most important issue in ovarian cancer prognosis is maximal cytoreductive surgery, with no residual disease at completion of initial surgery.

Third S. S. Ratnam Memorial Lecture 2007. Ovarian cancer: Is there hope for women?

Ovarian cancer is today the most lethal female cancer with an overall survival of only 49.9%. The currently available screening modalities are disappointing in detecting highly curable early stage ovarian cancer. Natural history of ovarian cancer is unknown; it appears it can develop quickly from normal looking ovaries. Timely referral of women with non-specific symptoms (such as abdominal bloating, pelvic pain) for an ultrasound scan or blood CA125 assessments may help in the early diagnosis. Patients with Stage IA or IB disease with grade 1 tumors have a cure rate of >90%; this is likely to be compromised by laparoscopic surgery. In selected patients fertility preservation with good obstetric outcome is possible. However, the relapse rate in 'high risk' early stage ovarian cancers is 40-45%; adjuvant chemotherapy is needed. Only 20-25% of those with stage III and IV disease are cured. Despite a high primary response (70%) majority (70-75%) will relapse and all are likely to succumb. Optimal debulking surgery followed by adjuvant chemotherapy are needed for stages III and IV disease; the outcome is superior if managed by gynecologic oncologists. Where cost of drugs is an important consideration, an alternative is carboplatin (an affordable and equally effective drug). The role of vaccines needs further study. When relapses occur palliation will be the aim in most instances. Oral contraceptives, breast feeding, tubal sterilization and hysterectomy also have a protective effect. Risk-reducing salpingo-oopherectomy has been suggested in women with BRCA mutations.

Determination of quality of life-related utilities for health states relevant to ovarian cancer diagnosis and treatment

Objectives (1) To define a set of health state descriptions related to screening, diagnosis, prognosis, and toxicities relevant to ovarian cancer; (2) To derive a set of quality of life-related utilities to be used for cost-effectiveness analyses. Methods A comprehensive list of health states was developed to represent the experiences of diagnostic testing for ovarian cancer, natural history of ovarian cancer (e.g., newly diagnosed early stage ovarian cancer, recurrent progressive ovarian cancer) and the most common chemotherapy-related toxicities (e.g. alopecia, peripheral neuropathy, pain, neutropenia, fatigue). Valuation of each health state was obtained through individual interviews of 13 ovarian cancer patients and 37 female members of the general public. Interviews employed visual analog score (VAS) and time trade off (TTO) methods of health state valuation. Results Mean TTO-derived utilities were higher than VAS-derived utilities by 0.118 U ( p < 0.0001). Mean VAS-derived utilities for screening tests were 0.83 and 0.81 for true negative blood test and ultrasound; 0.79 and 0.78 for false negative blood test and ultrasound, respectively. Patients and volunteers generally agreed in their preference ranking of chemotherapy-associated states, with lowest rankings being given to febrile neutropenia, grades 3–4 fatigue, and grades 3–4 nausea/vomiting. For 55% of chemotherapy-associated health states, the average utility assigned was higher for patients than for volunteers. Conclusions This study establishes societal preferences for a number of health states related to screening, diagnosis and treatment of ovarian cancer that can be used for assessing the cost-effectiveness of different ovarian cancer screening and treatment regimens.

Reducing ovarian cancer mortality through screening: Is it possible, and can we afford it?

ObjectiveOvarian cancer is a leading cause of cancer-related deaths among women. Given the low prevalence of this disease, the effectiveness of screening strategies has not been established. We wished to estimate the clinical impact and cost-effectiveness of potential screening strategies for ovarian cancer using population-specific data. MethodsA Markov state transition model to simulate the natural history of ovarian cancer in a cohort of women age 20 to 100. Age-specific incidence and mortality rates were obtained from SEER. Base-case characteristics of a potential screening test were sensitivity 85%, specificity 95%, and cost $50. Outcome measures were mortality reduction, lifetime number of false positive screening tests, positive predictive value, years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (ICER, in cost/YLS). ResultsModel-predicted lifetime risk of ovarian cancer (1.38%), lifetime risk of death from ovarian cancer (0.95%), and stage distribution (stage I-19%; stage II-7%; stage III, IV, or unstaged — 74%) closely approximated SEER data. Annual screening resulted in 43% reduction in ovarian cancer mortality, with ICER of $73,469/YLS (base case) and $36,025/YLS (high-risk population) compared to no screening. In the base case, the average lifetime number of false positive tests is 1.06. Cost-effectiveness of screening is most sensitive to test frequency, specificity and cost. ConclusionsAnnual screening for ovarian cancer has the potential to be cost effective, particularly in high-risk populations. Clinically acceptable positive predictive values are achieved if specificity exceeds 99%. Mortality reduction above 50% may not be achievable without screening intervals less than 12 months.

Serum CA125 level before the development of ovarian cancer

BackgroundLittle is known about the natural history of ovarian cancer with respect to the change of serum CA125 level. MethodsThe Shizuoka Cohort Study on Ovarian Cancer Screening (SCSOCS) Trial contains approximately 100,000 data on serum tumor marker CA125 prospectively obtained from more than 70,000 women. We reviewed the clinical charts and collected serum samples 2 months to 9.4 years prior to the surgery were available. ResultsIn 396 (95%) of the 419 patients with ovarian cancer, one serum sample was present before the diagnosis (mean, 4.1 years). The change of CA125 level before the diagnosis of ovarian cancer could be clearly separated into two groups according to the length of the following intervals: 47% (107/228) of patients with non-serous-type ovarian cancers develop secondarily from slightly elevated CA125 level (35 <CA125 <65 U/ml), with a mean interval of 3.8 years. On the other hand, 75% (126/168) of patients with serous-type ovarian cancer seem to develop suddenly from a normal CA125 level (CA125 <35 U/ml), with a mean interval of 1.4 years (p=0.011). ConclusionsThe slightly elevated CA125 level is typically present many years before the diagnosis especially in patients with non-serous-type ovarian cancer. However, serous-type ovarian cancer may exhibit a rapid progression possibly through de novo carcinogenesis.

Modern Chemotherapy Management of Recurrent Ovarian Cancer: A Multicentre Study

AimsThe natural history of ovarian cancer has changed over the last 10 years due to more effective drug treatments. The aim of this multicentre audit of the management of recurrent ovarian cancer was to examine the usage of newer drugs in light of the publication of National Institute of Clinical Excellence guidance. Materials and methodsAll patients presenting with a first or subsequent relapse of ovarian cancer between August 2001 and February 2003 in nine UK National Health Service centres were identified. Data were recorded retrospectively and prospectively from point of entry into the study and included the modality of primary cancer treatment, the treatment of each subsequent relapse and outcome. ResultsIn total, 245 evaluable patients were entered on to the database. The mean age was 62 years. All patients received a platinum-based chemotherapy regimen as first-line treatment. One hundred and fifty-five patients (63%) went on to receive third-line chemotherapy and 82 (34%) received fourth-line chemotherapy. The median survival from first relapse was estimated to be in excess of 12 months from our data. The efficacies of the chemotherapy agents used are comparable with the results of published phase III trials. ConclusionThis study shows that multicentre audit is feasible and provides useful information on current clinical practice on which to base future research.

Long-Term Follow-up of the Stockholm Screening Study on Ovarian Cancer

Objectives. Seventy percent of ovarian cancer is diagnosed at advanced stages. Having a method for early diagnosis is a very attractive concept. Several attempts have been made, using monoclonal antibody-based immunoassays, ultrasound, or combinations of both, to identify methods that might prove to be sufficiently sensitive and specific as a screening test. Despite promising results, a mortality study of a large population has yet to be completed due in part to the high cost involved.Methods. One of the first studies aimed at devising a screening strategy for ovarian cancer used the CA 125 immunoassay followed by ultrasound. The study was performed in Stockholm from 1986 through 1988. Ten years now having passed, an analysis has been performed to further evaluate the results of that study.Results. Screening led to the diagnosis of ovarian cancer in six patients, five of whom have since died of the disease. By searching the Cancer Registry, we were able to identify 20 ovarian cancer patients who developed the disease after the screening period. Of these, 12 died of the disease, 2 are alive with disease, and 6 have no evidence of disease following treatment. The median survival for patients diagnosed by screening was 100 months. Median survival for ovarian cancer patients identified subsequent to screening was 20 months. Although there was no difference in survival between these two groups, median survival was better for women diagnosed by screening (borderline significance, P = 0.059).Conclusion. These results indicate that a study of a large number of women with a sufficiently long observation time will be required to establish whether or not screening can reduce ovarian cancer mortality. Such a study may also provide insight into the natural history of ovarian cancer.

Characterization of Human Ovarian Carcinomas in a SCID Mouse Model

This study characterizes a murine model which is promising for the study of the growth and natural history of ovarian cancer and for testing of new therapies for its treatment. Intact portions of 20 different human ovarian cancer surgical specimens were implanted in over 60 severe combined immunodeficient (SCID) mice using techniques previously developed in our laboratory. Growth of xenografts was evaluated by gross examination and histopathologic analysis. Confirmation of the human origin of the tumor outgrowth was obtained usingin situhybridization analysis. By histological evaluation, all of the patients' tumors showed evidence of invasive growth in at least 1 of the mice implanted with portions of each surgical specimen and these tumors remained morphologically similar to the parent tumors for a long period of time. Furthermore, 65% (13/20) of the xenografts grew rapidly enough (i.e., reached a diameter of 1–2 cm within 2–6 months) to allow passage to subsequent SCID mice. Among the passaged xenografts, 3 eventually developed metastases in a distribution pattern similar to that of naturally occurring ovarian cancer and 2 developed ascites without evidence of further metastatic spread. Upon evaluation of sera from tumor-bearing mice, human antibodies presumably derived from immunoglobulin-secreting cells present in the original tumor specimen were identified. In support of this, human B cells and plasma cells could be seen within the tumor xenograft for more than 6 months following implantation. In summary, transplantation of surgical specimens from ovarian cancer patients into SCID mice results in an attractive model for the study of the natural history of ovarian cancer and may also be useful for analysis or new experimental therapeutic approaches for the treatment of this disease.

Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation.

It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastases from one primary ovarian cancer. The purpose of this study was to investigate whether ovarian cancer has a monoclonal or polyclonal origin. DNA specimens were obtained from peripheral blood lymphocytes (normal DNA) and from multiple tumor deposits of 17 women with epithelial ovarian carcinoma: primary tumors, metastatic deposits, and ascites. The clonal origin of each tumor was determined by performing (a) analysis to detect loss of heterozygosity at five loci on chromosomes 5, 11, 13, and 17; (b) sequencing of exons 5-8 of the p53 gene; and (c) X-chromosome inactivation analysis of the phosphoglycerate kinase (PGK) gene. In 15 of the 17 cases analyzed, there was clear evidence of monoclonal origin. The probability that the genetic events documented in these 15 cases occurred as independent events in each tumor deposit ranged from 2.5 x 10(-1) to 3.7 x 10(-16). In two cases, the pattern of allelic deletion and p53 gene mutation was compatible with either a monoclonal origin or origin from two primary ovarian tumors. The results did not support the hypothesis that ovarian cancer is a multifocal, polyclonal disease. Instead, the data suggest that sporadic epithelial ovarian carcinoma has either a monoclonal or a dual primary origin. These findings have important implications for understanding of the natural history of ovarian cancer and for clinical strategies aimed at prevention and early detection. Further studies will be required to determine the clonal origin of familial hereditary ovarian cancer.