Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: A meta-analysis
TL;DR: For advanced-stage ovarian cancer treated during the platinum-taxane era, the proportions of patients left with no gross residual disease and receiving intraperitoneal chemotherapy are independently significant factors associated with the most favorable cohort survival time.
About: This article is published in Gynecologic Oncology.The article was published on 2013-09-01. It has received 333 citations till now. The article focuses on the topics: Survival analysis & Cohort.
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TL;DR: For selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are noninferior to primary cytoreductive and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality.
Abstract: PurposeTo provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer.MethodsThe Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature.ResultsFour phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are noninferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality.RecommendationsAll women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and ...
329 citations
TL;DR: This text will inform the reader of recent updates to the scientific literature regarding the origin, aetiology and molecular-genetic basis of high-grade serous ovarian cancer (HGSOC) and provide a detailed overview of the clinical-pathological features of ovarian cancer.
Abstract: Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific discovery has fuelled recent ameliorations in the outcomes of many other cancers, the rates of mortality for ovarian cancer have been stagnant since around 1980. Yet despite the grim outlook, progress is being made towards better understanding the fundamental biology of this disease and how its biology in turn influences clinical behaviour. It has long been evident that ovarian cancer is not a unitary disease but rather a multiplicity of distinct malignancies that share a common anatomical site upon presentation. Of these, the high-grade serous subtype predominates in the clinical setting and is responsible for a disproportionate share of the fatalities from all forms of ovarian cancer. This review aims to provide a detailed overview of the clinical-pathological features of ovarian cancer with a particular focus on the high-grade serous subtype. Along with a description of the relevant clinical aspects of this disease, including novel trends in treatment strategies, this text will inform the reader of recent updates to the scientific literature regarding the origin, aetiology and molecular-genetic basis of high-grade serous ovarian cancer (HGSOC).
311 citations
TL;DR: The data suggest that removal of all evidence of macroscopic disease is associated with prolonged survival and should be the goal of primary cytoreductive surgery, as each incremental decrease in residual disease below 1 cm may be associated with an incremental improvement in overall survival.
Abstract: What constitutes "optimal" cytoreduction for women operated on for ovarian cancer remains uncertain. A majority of studies have employed a cutoff of 1-2 cm to define optimal cytoreduction. Recent studies suggest that removing all gross disease promotes disease-free survival compared to the current Gynecologic Oncology Group threshold of 1 cm or less of residual disease. This prospective database analysis reviewed the records of 465 patients with stage IIIC epithelial ovarian carcinoma (EOC) who had cytoreductive surgery in the years 1989-2003. All participants had bulky abdominal tumor, and maximal cytoreduction was attempted if technically possible. The patients, whose median age was 60 years, were followed up for a median of 38 months. Nearly all the patients received at least 6 cycles of platinum-based systemic chemotherapy. Univariate analysis showed age at the time of surgery and the preoperative platelet count to be significant continuous variables. Categorical variables with prognostic significance included the presence of ascites, the site of the largest tumor mass, extensive upper abdominal cytoreduction, and the extent of residual disease. Multivariate analysis confirmed age, the presence or absence of ascites, and the diameter of residual disease as being significant factors. Median survival was 106 months when there was no gross residual disease, and declined steadily as the amount of residual disease increased. Median survival was 34 months when patients were left with more than 2 cm of residual disease. The major distinctions with regard to survival rate were between no gross residual disease, 1 cm or less of gross disease, and more than 1 cm of residual disease. A trend toward improved survival was noted in patients left with 0.5 cm or less of residual disease compared with those retaining 0.6-1 cm of disease (Fig. 1). The investigators conclude from these findings that removing all evidence of gross stage IIIC EOC prolongs survival and is an appropriate goal of primary cytoreductive surgery. If complete gross resection is not feasible, as little residual tumor as possible should be left behind. An incremental decrease in residual disease below 1 cm can incrementally enhance overall survival.
287 citations
TL;DR: A cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations.
268 citations
TL;DR: The case is presented that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy, and the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer.
Abstract: Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer.
264 citations
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TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Abstract: The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
52,293 citations
TL;DR: In this paper, the authors compared two combinations, cisplatin and cyclophosphamide and paclitaxel, in women with ovarian cancer, and found that the alkylating agent and a platinum coordination complex have high response rates in advanced ovarian cancer.
Abstract: Background Chemotherapy combinations that include an alkylating agent and a platinum coordination complex have high response rates in women with advanced ovarian cancer. Such combinations provide long-term control of disease in few patients, however. We compared two combinations, cisplatin and cyclophosphamide and cisplatin and paclitaxel, in women with ovarian cancer. Methods We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin (75 mg per square meter of body-surface area) with either cyclophosphamide (750 mg per square meter) or paclitaxel (135 mg per square meter over a period of 24 hours). Results Three hundred eighty-six women met all the eligibility criteria. Known prognostic factors were similar in the two treatment groups. Alopecia, neutropenia, fever, and allergic reactions were reported more frequently in the cisplatin–paclitaxel group. Among 216 women with measurable disease, 73 percent in the cisplatin–pacli...
2,660 citations
TL;DR: Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment, while survival in patients with optimally debulked stage III ovarian cancer improved.
Abstract: Background Standard chemotherapy for newly diagnosed ovarian cancer is a platinum–taxane combination. The Gynecologic Oncology Group conducted a randomized, phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer. Methods We randomly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 (intravenous-therapy group) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 (intraperitoneal-therapy group). Treatment was given every three weeks for six cycles. Quality of life was assessed. Results Of 429 patients who underwent randomization, 415 were eligible. Grade 3...
2,349 citations
"Survival impact of complete cytored..." refers result in this paper
...Of these 15 studies, 4 studies [18–21] were ancillary data studies which retrospectively reanalyzed the data collected for 9 previous randomized prospective trials [5,6,23,30–35], and these ancillary data studies included overlapping data with two other studies [5,23]....
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TL;DR: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin pluspaclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus pac Litaxel.
Abstract: Purpose: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. Patients and Methods: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). Results: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabol...
1,929 citations
"Survival impact of complete cytored..." refers result in this paper
...Of these 15 studies, 4 studies [18–21] were ancillary data studies which retrospectively reanalyzed the data collected for 9 previous randomized prospective trials [5,6,23,30–35], and these ancillary data studies included overlapping data with two other studies [5,23]....
[...]
TL;DR: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables.
Abstract: PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy. MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication. RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P < .001). Each 10% increase in maximal cytoreduction was associat...
1,923 citations