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A framework for a personalized surgical approach to ovarian cancer.

ABSTRACT: The standard approach for the treatment of advanced-stage ovarian cancer is upfront cytoreductive surgery followed by a combination of platinum-based and taxane-based chemotherapy. The extent of residual disease following upfront cytoreductive surgery correlates with objective response to adjuvant chemotherapy, rate of pathological complete response at second-look assessment operations, and progression-free survival and overall survival. Contemporary data and meta-analyses indicate a correlation between volume of residual disease and patient outcome, with those patients undergoing complete gross resection having the best outcomes. Thus, attention has focused on surgical efforts to remove as much disease as possible with the metric of 'optimal' cytoreduction being R0 disease. Because patients with R0 resection seem to have the best overall outcomes, preoperative or intraoperative assessment to avoid unnecessary primary debulking surgery has become common. The use of serum CA-125 levels, physical examination and CT imaging have lacked accuracy in determining if disease can be optimally debulked. Therefore, an algorithm that identifies patients in whom complete gross resection at primary surgery is likely to be achieved would be expected to improve patient survival. We discuss contemporary definitions of 'optimal' residual disease, and opportunities to personalize surgical therapy and improve the quality of surgical care.

SUBMITTER: Nick AM

PROVIDER: S-EPMC4528308 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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A framework for a personalized surgical approach to ovarian cancer.

Nick Alpa M AM Coleman Robert L RL Ramirez Pedro T PT Sood Anil K AK

Nature reviews. Clinical oncology 20150224 4

The standard approach for the treatment of advanced-stage ovarian cancer is upfront cytoreductive surgery followed by a combination of platinum-based and taxane-based chemotherapy. The extent of residual disease following upfront cytoreductive surgery correlates with objective response to adjuvant chemotherapy, rate of pathological complete response at second-look assessment operations, and progression-free survival and overall survival. Contemporary data and meta-analyses indicate a correlation ...[more]

PMID: 25707631

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Project description:Study objectiveTo evaluate the effect of surgical approach on overall survival (OS) for women with advanced, epithelial ovarian cancer (EOC) after neoadjuvant chemotherapy (NACT) and determine the sociodemographic and clinical factors associated with surgical approach.DesignThe primary exposure was surgical approach to interval cytoreduction, minimally invasive versus open, and was evaluated by intention to treat. Primary outcome was OS. Associations were examined using Chi-squared tests, Wilcoxon rank sum tests, and multivariate logistic regression. Survival analysis was performed with Kaplan-Meier methods and Cox proportional hazards.SettingThe National Cander Database was used to identify eligible patients.PatientsWomen diagnosed with stage IIIC/IV EOC from 2010-2016.InterventionsPatients were included if they were treated with NACT within 90 days of diagnosis before interval cytoreductive surgery (CRS).Measurements and main resultsA total of 8085 women were identified; 6713 (83%) underwent open interval CRS, and 1372 (17%) underwent minimally invasive interval CRS. The proportion undergoing minimally invasive CRS after NACT increased from 2% in 2010 to 11% in 2016, a nearly 6-fold increase. There was no difference in OS between women who underwent minimally invasive and open interval CRS (median OS 36.5 vs 35.2 months, HR 0.94, 95% CI, 0.86-1.04). After adjusting for demographic and clinical variables, including age, race, ethnicity, income, and Charlson/Deyo score, no difference in OS was observed (HR 0.95, 95% CI, 0.86-1.04). Women of older age (OR 1.35, 95% CI, 1.05-1.74) and Hispanic ethnicity (OR 1.46, 95% CI, 1.14-1.88) had increased odds of receiving minimally invasive CRS after NACT, whereas low income (<$38000/year) women had decreased odds (OR 0.76, 95% CI, 0.60-0.97, p = .03). Length of stay differed for patients undergoing minimally invasive versus open interval CRS (3 vs 5 days, p <.01), but there was no difference in need for postoperative readmission.ConclusionsMinimally invasive CRS has similar survival outcomes to open CRS among women with EOC who have undergone NACT.

Project description:ContextThe abysmal outlook of urothelial cancer (UC) has changed with the introduction of immunotherapy. Still, many patients do not respond and distinctive biomarkers are currently lacking. The rise of this novel armamentarium of immunotherapy treatments, in combination with the complex biology of an immunological tumor response, warrants the development of a comprehensive framework that can provide an overview of important immunological processes at play in individual patients.ObjectiveTo develop a comprehensive framework based on tumor- and host-specific parameters to understand immunotherapy response in UC. This framework can inform rational, biology-driven clinical trials and ultimately guide us toward individualized patient treatment.Evidence acquisitionA literature review was conducted on UC immunotherapy, clinical trial data, and biomarkers of response to checkpoint inhibition.Evidence synthesisHere, we propose a UC immunogram, based on currently available clinical and translational data. The UC immunogram describes several tumor- and host-specific parameters that are required for successful immunotherapy treatment. These seven parameters are tumor foreignness, immune cell infiltration, absence of inhibitory checkpoints, general performance and immune status, absence of soluble inhibitors, absence of inhibitory tumor metabolism, and tumor sensitivity to immune effectors.ConclusionsLongitudinal integration of individual patient parameters may ultimately lead to personalized and dynamic immunotherapy, to adjust to the Darwinian forces that drive tumor evolution. Incorporating multiparameter biomarkers into quantitative predictive models will be a key challenge to integrate the immunogram into daily clinical practice.Patient summaryHere, we propose the urothelial cancer immunogram, a novel way of describing important immunological characteristics of urothelial cancer patients and their tumors. Seven characteristics determine the chance of having an immunological tumor response. Using this immunogram, we aim to better understand why some patients respond to immunotherapy and some do not, to ultimately improve anticancer therapy.

Project description:BackgroundSecondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation.MethodsWe randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival.ResultsA total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery.ConclusionsIn this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.).

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A framework for a personalized surgical approach to ovarian cancer.

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A framework for a personalized surgical approach to ovarian cancer.

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