Optimal Surgical Cytoreduction Research Articles

Preoperative serum level of CA153 and a new model to predict the sub-optimal primary debulking surgery in patients with advanced epithelial ovarian cancer

ObjectiveThe aim of this study was to establish a preoperative model to predict the outcome of primary debulking surgery (PDS) for advanced ovarian cancer (AOC) patients by combing Suidan predictive model with HE4, CA125, CA153 and ROMA index.Methods76 AOC Patients in revised 2014 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent PDS between 2017 and 2019 from Yunnan Cancer Hospital were included. Clinical data including the levels of preoperative serum HE4, CA125, CA153 and mid-lower abdominal CT-enhanced scan results were collected. The logistics regression analysis was performed to find factors associated with sub-optimal debulking surgery (SDS). The receiver operating characteristic curve was used to evaluate the predictive performances of selected variables in the outcome of primary debulking surgery. The predictive index value (PIV) model was constructed to predict the outcome of SDS.ResultsOptimal surgical cytoreduction was achieved in 61.84% (47/76) patients. The value for CA125, HE4, CA153, ROMA index and Suidan score was lower in optimal debulking surgery (ODS) group than SDS group. Based on the Youden index, which is widely used for evaluating the performance of predictive models, the best cutoff point for the preoperative serum HE4, CA125, CA153, ROMA index and Suidan score to distinguish SDS were 431.55 pmol/l, 2277 KU/L, 57.19 KU/L, 97.525% and 2.5, respectively. Patients with PIV≥5 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing SDS were 73.7%, 82.9%, 62.9% and 72.3%, respectively. In the constructed model, the AUC of the SDS prediction was 0.770 (95% confidence interval: 0.654-0.887), P<0.001.ConclusionPreoperative serum CA153 level is an important non-invasive predictor of primary SDS in advanced AOC, which has not been reported before. The constructed PIV model based on Suidan's predictive model plus HE4, CA125, CA153 and ROMA index can noninvasively predict SDS in AOC patients, the accuracy of this prediction model still needs to be validated in future studies.

The Effect of Upper Abdominal Surgery on Complication Profile in Ovarian Cancer.

Introduction: Due to the superficial peritoneal spread of ovarian cancer, upper abdominal surgical procedures are often required to achieve optimal surgical cytoreduction. This study compares the mortality and morbidity rates of patients undergoing upper and lower abdominal cytoreductive surgery in our institution. Material and Methods: Patients who underwent cytoreductive surgery for ovarian malignancies from 2014 to 2020 were retrospectively identified from an institutional database. Upper abdominal cytoreduction was defined anatomically as debulking of disease proximal to the ligament of Treitz. Perioperative and postoperative outcomes were analyzed. Results: A total of 148 operations were performed. A single gynecologic oncologist performed all procedures. When all cytoreductive procedures were evaluated, diaphragm injury, blood transfusion, hospital stay, atelectasis, pneumonia, effusion, wound infection and need for intensive care were found to be statistically significantly higher in patients who underwent upper abdominal surgery compared to patients in the lower abdominal surgery group (p=0.001, p=0.017, p=0.002, p=0.045, p=0.006, p=0.005, respectively). Conclusion: In patients scheduled for cytoreductive surgery with the diagnosis of ovarian cancer, upper abdominal surgery is a viable procedure, although it carries a higher risk of complications compared to lower abdominal surgery alone. Upper abdominal surgery in advanced ovarian cancer can be applied to patients with an acceptable complication profile when the possible survival advantage is considered.

Experience With J-Plasma Device in Achieving Complete Cytoreduction in Patients With Ovarian Cancer.

Ovarian cancer remains one of the most lethal malignancies in women. Optimal surgical cytoreduction is the most important prognostic factor of survival in patients with advanced ovarian cancer. The helium gas plasma device (J-Plasma) has recently been introduced into surgical treatment of these patients with some promising results. The aim of this study was to evaluate the utility of J-Plasma in the debulking surgery of patients with ovarian cancer. A single center retrospective analysis of the characteristics of patients with ovarian cancer who had cytoreductive surgery with the use of J-Plasma device from January of 2020 until July of 2022 was conducted. A total of 13 patients were included in our study. Six patients were treated with primary debulking surgery, whereas seven underwent interval debulking surgery after neoadjuvant chemotherapy. Complete cytoreduction was achieved in nine patients (64%), and CC-1 in four patients. Most of the patients did not face any major complications; only 1 patient suffered from small bowel fistula that needed relaparotomy. J-Plasma can safely be used in ovarian cancer debulking surgeries performed by gynecologic oncologists in tertiary centres. This technology can safely increase the complete cytoreduction rates.

Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis

This meta-analysis was conducted to evaluate the impact of BRCA mutations on survival outcomes of ovarian cancer patients and assess whether the BRCA status was an independent predictor of complete cytoreduction. We searched the PubMed, Cochrane, EMBASE, Scopus, Web of Science, and Google Scholar databases for studies that evaluated the associations among BRCA mutations, ovarian cancer survival and surgical cytoreduction before August 2021 based on specific inclusion and exclusion criteria. We identified 61 articles that compared the clinical features, survival outcomes, and optimal surgical cytoreduction rates between BRCA-positive patients and BRCA-negative patients. The results showed that BRCA mutation carriers were diagnosed with ovarian cancer at a younger age than the age at which nonmutation carriers were diagnosed. In addition, BRCA mutation carriers were more likely to be in the International Federation of Gynecology and Obstetrics (FIGO) stage III-IV, and the pathological grade was commonly grade 3. The pathological type of BRCA mutation carriers was more likely to be high-grade serous carcinoma. Patients with BRCA mutations had higher response rates to platinum-based chemotherapy than the noncarriers. However, patients in both groups had equivalent rates of surgical cytoreduction, and BRCA-positive patients had longer overall survival (OS) time (HR=0.65; 95% confidence interval [CI]: 0.59, 0.73; p < 0.001) and longer progression-free survival (PFS) (HR=0.72; 95% CI: 0.63, 0.82; p < 0.001). BRCA mutations appear to be associated with improved OS and PFS in patients with ovarian cancer. However, we did not find any difference in the surgical resection rate between participants in the two groups.

Obesity is associated with poor clinical outcomes in BRCA mutation carriers with epithelial ovarian cancer

<h3>Objectives:</h3> Mutations in <i>BRCA1</i> and <i>BRCA2</i> increase the risk of epithelial ovarian cancer (EOC). Emerging evidence suggests obesity may influence <i>BRCA</i> tumor biology; body mass index (BMI) appears to correlate with DNA damage in breast epithelium in <i>BRCA</i> women. We hypothesized that obesity negatively influences tumor biology in <i>BRCA</i> women with EOC, and sought to identify correlations with BMI and clinical outcomes in this population. <h3>Methods:</h3> We performed an IRB approved retrospective study. We identified patients with <i>BRCA</i>-associated EOC diagnosed between 1990-2015. All women underwent surgical resection with platinum-based chemotherapy. We abstracted clinical and pathologic data, and calculated BMI at the time of diagnosis. Obesity was examined per WHO criteria of normal weight, overweight, class I obesity, and class II obesity. We performed descriptive statistics with Kaplan-Meier, Cox Proportional Hazards Regression, and univariate analyses. <h3>Results:</h3> We identified 179 women meeting criteria. Most were <i>BRCA1</i> (125, or 70%); 53 (30%) were <i>BRCA2</i>; and 1 had both a <i>BRCA1</i> and <i>BRCA2</i> mutation. The majority had stage III/IV disease (137, 77%) and grade 3 serous histology (168, 94%); 150 patients underwent optimal cytoreduction (87%). BMI was distributed throughout the WHO strata: 101 women had normal weight; 46 were overweight; 20 had class I obesity; 12 had class II obesity. Age, medical comorbidities, and rates of optimal surgical cytoreduction were similar among these groups. In a subcohort of patients with stage III/IV disease, we identified a significant trend between increased BMI strata and poor disease-free survival (35, 32, 25, and 13.5 months, <i>p</i>=0.003). This was also observed for overall disease-specific survival (132, 144, 112, and 72.5 months, <i>p</i>=0.0306). Multivariable analyses of the entire cohort confirmed that age (<i>p</i>=0.035), stage (<i>p</i><0.001), and BMI (<i>p</i>=0.017) remained significant independent prognosticators after controlling for grade and optimal cytoreduction. <h3>Conclusions:</h3> We identified a significant and independent association between BMI and clinical outcome in <i>BRCA</i> positive women with EOC. Factors associated with obesity may negatively influence <i>BRCA</i> associated ovarian cancer biology, and suggest this may be a modifiable risk factor to target for therapy.

The Capacity of the Ovarian Cancer Tumor Microenvironment to Integrate Inflammation Signaling Conveys a Shorter Disease-free Interval.

Ovarian cancer has one of the highest deaths to incidence ratios across all cancers. Initial chemotherapy is effective, but most patients develop chemoresistant disease. Mechanisms driving clinical chemo-response or -resistance are not well-understood. However, achieving optimal surgical cytoreduction improves survival, and cytoreduction is improved by neoadjuvant chemotherapy (NACT). NACT offers a window to profile pre- versus post-NACT tumors, which we used to identify chemotherapy-induced changes to the tumor microenvironment. We obtained matched pre- and post-NACT archival tumor tissues from patients with high-grade serous ovarian cancer (patient, n = 6). We measured mRNA levels of 770 genes (756 genes/14 housekeeping genes, NanoString Technologies), and performed reverse phase protein array (RPPA) on a subset of matched tumors. We examined cytokine levels in pre-NACT ascites samples (n = 39) by ELISAs. A tissue microarray with 128 annotated ovarian tumors expanded the transcriptional, RPPA, and cytokine data by multispectral IHC. The most upregulated gene post-NACT was IL6 (16.79-fold). RPPA data were concordant with mRNA, consistent with elevated immune infiltration. Elevated IL6 in pre-NACT ascites specimens correlated with a shorter time to recurrence. Integrating NanoString (n = 12), RPPA (n = 4), and cytokine (n = 39) studies identified an activated inflammatory signaling network and induced IL6 and IER3 (immediate early response 3) post-NACT, associated with poor chemo-response and time to recurrence. Multiomics profiling of ovarian tumor samples pre- and post-NACT provides unique insight into chemo-induced changes to the tumor microenvironment. We identified a novel IL6/IER3 signaling axis that may drive chemoresistance and disease recurrence.

Growing Teratoma Syndrome a Rare Clinical Entity: Two Decades Management Experience from the Regional Cancer Institute.

To study the clinical, biochemical, radiological, pathological characteristics, surgical treatment details, and follow-up of growing teratoma syndrome (GTS) patients. This is a retrospective study of GTS treated in the Department of Gynaecological Oncology at a regional cancer institute from March 2000 to March 2020. A total of 303 cases of germ cell ovarian cancers were treated, and 8 (2.6%) of 303 cases recurred as GTS during this period. The patients presenting with recurrent GTS were studied for clinical, radiological, tumor markers, surgical management, histopathology, and post-operative follow-up details that were analyzed retrospectively. The Kaplan-Meier curve was used for the survival analysis. The 8 out of 303 cases of germ cell ovarian cancers recurred as GTS and the incidence rate is 2.6% during this period. In the six (75%) of eight cases, the histopathology report was immature teratoma ovaries. The five cases (62.5%) were in advanced stage. All the eight recurrent GTS cases received optimal surgical cytoreduction. The overall disease-free survival is 85.7% and one patient has recurrence after the surgery for GTS at 23rd month of follow-up visit. All the patients are alive till date. The GTS represents a rare clinical and pathological phenomenon. Nevertheless, GTS should be considered as one of the differential diagnosis in young patients having normal tumor markers with recurrent carcinomatosis following the primary treatment germ cell tumors of ovaries. The optimal cytoreduction of recurrent GTS leads to prolonged survival and possible cure in young patients.

Preoperative serum levels of HE4 and CA125 predict primary optimal cytoreduction in advanced epithelial ovarian cancer: a preliminary model study

ObjectiveThe aim of this study is to establish a noninvasive preoperative model for predicting primary optimal cytoreduction in advanced epithelial ovarian cancer by HE4 and CA125 combined with clinicopathological parameters.MethodsClinical data including preoperative serum HE4 and CA125 level of 83 patients with advanced epithelial ovarian cancer were collected. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of each clinical parameter were calculated. The Predictive Index score model and the logistic model were constructed to predict the primary optimal cytoreduction.ResultsOptimal surgical cytoreduction was achieved in 62.65% (52/83) patients. Cutoff values of preoperative serum HE4 and CA125 were 777.10 pmol/L and 313.60 U/ml. (1) Patients with PIV ≥ 6 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing suboptimal cytoreduction were 71, 100, 68, and 100%, respectively. (2) The logistic model was: logit p = 0.12 age − 2.38 preoperative serum CA125 level − 1.86 preoperative serum HE4 level-2.74 histological type-3.37. AUC of the logistic model in the validation group was 0.71(95%CI 0.54–0.88, P = 0.025). Sensitivity and specificity were 1.00 and 0.44, respectively.ConclusionAge, preoperative serum CA125 level and preoperative serum HE4 level are important non-invasive predictors of primary optimal surgical cytoreduction in advanced epithelial ovarian cancer. Our PIV and logistic model can be used for assessment before expensive and complex predictive methods including laparoscopy and diagnostic imaging. Further future clinical validation is needed.

Survival Impact of Optimal Surgical Cytoreduction in Recurrent Epithelial Ovarian Cancer with Brain Metastasis

Aim: The aim of this study was to determine the clinicopathological characteristics, treatment details and outcome of patients with brain metastasis from epithelial ovarian carcinoma (EOC). Methods: This study included 21 patients diagnosed with brain metastasis from EOC between 1999 and 2009. Results: Median age was 61 years (range 38-77). The median time elapsed from EOC diagnosis to brain metastasis detection was 32 months. Single brain metastases were found in 10 (48%) cases, and there was extra-cranial disease in 11 (52%) cases. During the mean 86 months of follow-up, 18 of the patients (86%) died of the disease and 3 (14%) were alive with disease. The median survival time after the initial diagnosis of brain metastasis was 9 months. The median overall survival (OS) from initial diagnosis of EOC was 50 months. In univariate analysis, prolonged time from initial diagnosis to central nervous system metastasis (more than 32 months) (p = 0.001), treatment with radiotherapy (p < 0.001), optimal cytoreductive operation (p = 0.02) were all positively correlated with OS. Conclusion: The prognosis of patients with brain metastasis from EOC is still poor. The significant predictors of survival in our series were whole brain radiotherapy, prolonged elapsed time from initial diagnosis to brain metastasis and optimal cytoreductive surgery.

Abstract A57: Adoptive T cell therapy for ovarian cancer: Application of a surgically relevant model

Abstract Ovarian cancer is the most lethal gynecologic cancer, with more than 20,000 new diagnoses and 15,000 cancer-related deaths annually. Current standard therapy for advanced ovarian cancer incorporates upfront surgical cytoreduction followed by cytotoxic chemotherapy. But even with advances in surgical technique, chemotherapeutics and targeted delivery methods, the overall five-year survival rate remains ~50%, highlighting the need for novel treatment strategies. We have focused our efforts on immunotherapy by adoptive transfer of engineered T cells that can target proteins uniquely overexpressed in ovarian cancer. Recent work has identified mesothelin (MSLN) as a potential target, as this protein is overexpressed in malignant ovarian tissue, promotes the oncogenic phenotype, and has limited expression in healthy cells. Preclinical studies have demonstrated that mouse and human T cells engineered to express T cell receptors (TCR) with high-affinity for MSLN kill respectively murine and human ovarian tumor cells in vitro. Furthermore, in vivo studies in mice treating metastatic disease developing after intraperitoneal introduction of mouse ID8 ovarian cancer cells have demonstrated that engineered, adoptively transferred T cells preferentially accumulate in ID8 ovarian cancers, reduce tumor burden and prolong survival. However, our results also revealed that the tumor microenvironment (TME) can limit the persistence and killing capacity of engineered T cells. Immunosuppressive cells, inhibitory ligands that reduce T cell function, and cell death-inducing ligands are abundant within ID8 tumors, and cellular and molecular analyses of human ovarian cancer specimens showed that human T cell therapy will face similar TME-mediated obstacles. The ovarian cancer TME is also a nutrient- and oxygen-deprived milieu, and the adaptive metabolic responses required for survival by infiltrating T cells have protean effects on T cell function. Thus, strategies that modulate T cell responses to inhibitory signals, including metabolic pathways, have the potential to influence activity in the TME, and to enhance T cell function and improve anti-tumor efficacy. Ongoing studies exploring strategies to overcome elements common to the human and murine TME, including both direct modulation of the microenvironment and engineering of T cells to overcome critical components of immune evasion by solid tumors and to promote T cell survival and function, will be discussed. Building upon this work, we have been developing a novel model that more directly reflects the clinical setting requiring intervention. Following orthotopic injection of ID8 ovarian cancer cells directly beneath the ovarian bursa, tumorigenesis occurs initially within the ovary/fallopian tube microenvironment, and is followed by development of small volume metastatic disease. This orthotopic model, which results in formation of intraperitoneal metastatic implants originating from the ovary, replicates the development and patterns of metastatic spread of human ovarian cancer. Following intervention with primary surgical cytoreduction that includes hysterectomy and bilateral salpingo-oophorectomy, mice are being treated by adoptive transfer of antigen-specific T cells to target minimal residual disease in the peritoneal cavity, which models the clinical situation of patients requiring treatment after optimal surgical cytoreduction. Ongoing studies will be discussed that have been designed to modulate the function and persistence of transferred, MSLN-specific T cells and assess the impact on in vivo tumor development and survival in this clinically relevant model of ovarian cancer treatment. Citation Format: Christopher B. Morse, Kristin G. Anderson, Breanna M. Bates, Edison Y. Chiu, Nicolas M. Garcia, Philip D. Greenberg. Adoptive T cell therapy for ovarian cancer: Application of a surgically relevant model [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A57.

Do differences in medical comorbidities and treatment impact racial disparities in epithelial ovarian cancer?

BackgroundPopulation-based studies of women with epithelial ovarian cancer suggest that black women have worse survival compared to white women. The primary objective of this study was to determine if, at a National Cancer Institute (NCI)-Designated Comprehensive Cancer Center (CCC) serving a diverse racial and socioeconomic population, race is independently associated with differences in survival. MethodsA retrospective review of women with EOC diagnosed between 2004–2009 undergoing treatment with follow-up at our institution was performed.Records were reviewed for demographics, comorbidities (as defined by the Charlson Comorbidity Index (CCI)), tumor characteristics, treatment, progression-free (PFS), and overall survival (OS). Survival was calculated using the Kaplan-Meier method and compared with the log-rank test. Multivariate survival analysis was performed with Cox (proportional hazards) model. Results367 patients met inclusion criteria. 54 (15%) were black and 308 (84%) were white. Compared to white women, black women had higher BMI, lower rates of optimal surgical cytoreduction, lower rates of intraperitoneal chemotherapy, and higher CCI scores. The median PFS for black and white women were 9.7 and 14.6months, respectively (p=0.033). The median overall survival was 21.7months for black women and 42.6months for white women (p<0.001). On multivariate analysis, black race independently correlated with a worse overall survival (HR 1.61, 95% CI 1.06–2.43). ConclusionIn this cohort, racial disparities may be due to higher medical comorbidities and lower rates of optimal surgical cytoreduction. After accounting for these differences, race remained an independent predictor of worse overall survival.

Correlation between Surgeon's assessment and radiographic evaluation of residual disease in women with advanced stage ovarian cancer reported to have undergone optimal surgical cytoreduction: An NRG Oncology/Gynecologic Oncology Group study

PurposeWe sought to determine the level of concordance among surgeons' assessment of residual disease (RD) and pre-treatment computed tomography (CT) findings among women who underwent optimal surgical cytoreduction for advanced stage ovarian cancer. MethodsThis is a post-trial ad hoc analysis of a phase 3 randomized clinical trial evaluating the impact of bevacizumab in primary and maintenance therapy for patients with advanced stage ovarian cancer following surgical cytoreduction. All subjects underwent imaging of the chest/abdomen/pelvis to establish a post-surgical baseline prior to the initiation of chemotherapy. Information collected on trial was utilized to compare surgeon's operative assessment of RD, to pre-treatment imaging. ResultsOf 1873 enrolled patients, surgical outcome was described as optimal (RD≤1cm) in 639 subjects. Twelve patients were excluded as they did not have a baseline, pretreatment imaging, leaving 627 participants for analysis. The average interval from surgery to baseline scan was 26days (range: 1–109). In 251 cases (40%), the post-operative scan was discordant with surgeon assessment, demonstrating RD>1cm in size. RD>1cm was most commonly identified in the right upper quadrant (28.4%), retroperitoneal para-aortic lymph nodes (RD>1.5cm; 28.2%) and the left upper quadrant (10.7%). Patients with RD>1cm on pre-treatment CT (discordant) exhibited a significantly greater risk of disease progression (HR 1.30; 95% CI 1.08–1.56; p=0.0059). ConclusionsAmong patients reported to have undergone optimal cytoreduction, 40% were found to have lesions >1cm on postoperative, pretreatment imaging. Although inflammatory changes and/or rapid tumor regrowth could account for the discordance, the impact on PFS and distribution of RD may suggest underestimation by the operating surgeon.

Beyond the Beyond: First Case of 9 Cytoreductive Surgeries in a Long-Surviving Ovarian Cancer Patient: Case Report

The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients' prognosis has been reported. We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications. Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

The optimal time for surgery in women with serous ovarian cancer.

Advanced high-grade serous ovarian carcinoma (HGSC) is commonly treated with surgery and chemotherapy. We investigated the survival of patients treated with primary or interval surgery at different times following neoadjuvant chemotherapy. Their survival was compared with that of patients treated with primary cytoreductive surgery and adjuvant chemotherapy. Patients with stage III or IV HGSC were included in this retrospective cohort study. Clinical data were obtained from patient records. Patients were divided into 2 groups based on treatment with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) or with primary cytoreductive surgery and adjuvant chemotherapy (PCS). Study groups were stratified by several clinical variables. We included 334 patients in our study: 156 in the NAC and 178 in the PCS groups. Survival of patients in the NAC group was independent of when they underwent interval cytoreductive surgery following initiation of neoadjuvant chemotherapy (p < 0.001). Optimal surgical cytoreduction had no impact on overall survival in the NAC group (p < 0.001). Optimal cytoreduction (p < 0.001) and platinum sensitivity (p < 0.001) were independent predictors of improved survival in the PCS but not in the NAC group. Patients in the NAC group had significantly worse overall survival than those in the PCS group (31.6 v. 61.3 mo, p < 0.001). Women with advanced HGSC who underwent PCS had better survival than those who underwent interval NAC, regardless of the number of cycles of neoadjuvant therapy. Optimal cytoreduction did not provide a survival advantage in the NAC group.

Prediction of 5-year survival in advanced-stage ovarian cancer patients based on computed tomography peritoneal carcinomatosis index.

To evaluate whether the quantification of peritoneal metastases in advanced-stage ovarian cancer patients using the peritoneal carcinomatosis index, detected by CT (CT-PCI), correlates with the serum levels of tumor marker CA-125 and 5-year survival. The CT-PCI was determined in 82 patients with stage III or stage IV ovarian cancer using the Sugarbaker classification prior to cytoreductive surgery. Linear regression analysis was used to correlate CT-PCI and CA-125 levels. Correlation of presurgical CT-PCI, optimal surgical cytoreduction, and 5-year survival was established using binary logistic regression analysis. A score for prediction of 5-year survival probability was established using multivariate backwards binary logistic regression. Presurgical CT-PCI correlates significantly with presurgical CA-125 serum levels (r=0.487, P<0.001). Multivariate binary logistic regression suggested significantly improved 5-year survival with lower CT-PCI and lower ECOG performance scores. CT-PCI allows quantification of peritoneal disease in advanced-stage ovarian cancer patients, similar to CA-125. CT-PCI in combination with ECOG performance has the potential to help evaluate the 5-year survival probability.

Characteristics of 10-year survivors of high-grade serous ovarian carcinoma

Objectives: High-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor overall survival. However, the clinical features of long-term (LT; >10 years) survivors have not been well characterized. Methods: A multicenter research consortium was established among 5 participating academic centers in the United States. Patient selection criteria included a diagnosis of stage III/IV high-grade serous ovarian, fallopian tube, or primary peritoneal carcinoma with at least 10 years of follow-up from the date of initial diagnosis. Nonserous, borderline tumors and low-grade serous subtypes were excluded. Results: A total of 203 LT survivors with HGSC were identified. Median age at diagnosis was 57 years (range 37–84 years). Most patients had stage IIIC (72.4%) disease at presentation. Of those who underwent primary cytoreductive surgery, optimal cytoreduction (residual disease of no more than 1 cm in maximal diameter) was achieved in 143 (85.6%) patients, and 46.6% of all patients had a complete gross resection. After a median follow-up of 144 months, 88 (46.8%) patients did not develop recurrent disease. Twenty-one patients (11.2%) had 1 recurrence during the follow-up interval, 19 patients (10.1%) had 2 recurrences, and 60 patients (31.9%) had more than 2 recurrences. Of the 79 patients tested for BRCA1 and BRCA2 germline mutations, 43 (54.4%) carried a deleterious mutation. Of note, 24 (14%) patients had suboptimal cytoreductive surgery, 16 (11%) had a platinum-free interval of less than 12 months, and 100 (53%) with recurrent disease were surviving 10 or more years after diagnosis. Conclusions: Long-term survivors of advanced HGSC generally have clinical features including optimal surgical cytoreduction and platinum-sensitive disease. The majority of these patients will develop recurrent disease with many being treated with multiple therapeutic regimens. Future work will compare the clinical features of this LT survivor cohort of “exceptional” responders with the characteristics of HGSC patients with less favorable outcomes.

Optimal primary therapy of ovarian cancer

Epithelial ovarian cancer continues to have the highest case-fatality ratio of all gynecologic cancers, in spite of ongoing advances in risk-assessment, genomics, tumor biology, cytoreductive surgery, chemotherapy, and molecular-targeted interventions. Primary treatment options for advanced-stage disease not only should reflect current best standards, but also need to be tailored for individual patients, with consideration of local resources. Formulation of recommendations for optimal primary therapy based on a selective review of data from completed randomized trials, analysis of ongoing trials, and integration with current tumor biology, within the context of individualized clinical care. Recommendations were presented for discussion during an international meeting of experts in ovarian cancer treatment. Key recommendations include full adjuvant therapy for early-stage high-grade serous cancer; tailored utilization of neoadjuvant chemotherapy based on patient comorbidities, extent of disease, and likelihood of achieving optimal surgical cytoreduction; preferred utilization of carboplatin with weekly paclitaxel as primary therapy; consideration of intraperitoneal cisplatin-based therapy in appropriate patients; avoidance of maintenance chemotherapy; lack of necessity for bevacizumab during primary chemotherapy and primary maintenance; acknowledgement of research opportunities and priorities. Integrated multidisciplinary care, including cytoreductive surgery and platinum-based chemotherapy, remain central to the optimal management of women with advanced-stage ovarian cancer. However, even with recent technical advances, the impact on disease-related mortality is limited, and more attention will be focused on the early integration of research, particularly with neoadjuvant chemotherapy and interval cytoreductive surgery.

Characteristics of 10-year survivors of high-grade serous ovarian carcinoma

ObjectiveHigh-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor long-term (LT) survival. Here we describe clinical features found in women surviving HGSC for ten or more years. MethodsA multi-center research consortium was established between five participating academic centers. Patient selection criteria included high-grade serous ovarian, fallopian tube, or peritoneal carcinoma with at least ten years of follow up. Non-serous, borderline tumors and low-grade serous subtypes were excluded. ResultsThe 203 identified LT ten-year survivors with HGSC were diagnosed at a median age of 57years (range 37–84years). The majority of patients had stage IIIC (72.4%) disease at presentation. Of those who underwent primary cytoreductive surgery, optimal cytoreduction was achieved in 143 (85.6%) patients. After a median follow up of 144months, 88 (46.8%) patients did not develop recurrent disease after initial treatment. Unexpected findings from this survey of LT survivors includes 14% of patients having had suboptimal cytoreduction, 11% of patients having an initial platinum free interval of <12months, and nearly 53% of patients having recurrent disease, yet still surviving more than ten years after diagnosis. ConclusionsLT survivors of HGSC of the ovary generally have favorable clinical features including optimal surgical cytoreduction and primary platinum sensitive disease. The majority of patients will develop recurrent disease, however many remained disease free for more than 10years. Future work will compare the clinical features of this unusual cohort of LT survivors with the characteristics of HGSC patients having less favorable outcomes.

Optimal surgical cytoreduction of the upper abdomen and the diaphragm for advanced ovarian cancer using PlasmaJet™ energy

ObjectiveTo show the contribution of PlasmaJet™, technology using pur gaz plasma as electrically neutral source of energy to cut and coagulate tissue, in ovarian cancer surgery. MethodsA forty eight years old patient was diagnosed with an ovarian cancer. The first laparoscopy allowed one to make histological diagnosis (ovarian high-grade serous carcinoma) and determine that the disease was resecable, with a PCI to ten. The film shows the upper abdominal time of the cytoreduction surgery, using PlasmaJet™. ResultsThe surgery included: stripping of the peritoneum of the right diaphragm and full thickness diaphragmatic resection, stripping of the peritoneum of left diaphragm splenectomy, resection of the greater and the lesser omentums, pelvic lymphadenectomy and para-aortic lymphadenectomy, posterior pelvectomy (Hudson) and appendicectomy. There were no postoperative complications (short or medium term). ConclusionThe PlasmaJet seems to be a very interesting instrument in this type of surgery, particularly in the dissection of adherent pathological areas, as diaphragmatic domes can be.

A comparison of the toxicity and tolerability of two intraperitoneal chemotherapy regimens for advanced-stage epithelial ovarian cancer

ObjectivesRandomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC. MethodsRetrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan–Meier estimate; the log-rank test was used to compare survival curves. ResultsOf the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs 1.6%, p=0.033), grade 3 neuropathy (7.8% vs 0%, p=0.013) and grade 2–3 neutropenia (22.1% vs 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups. ConclusionIP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.