Suboptimal Debulking Surgery Research Articles

Recurrence Rate and Associated Factors of Primary Fallopian Tube Carcinoma in the South of Vietnam

Objectives: This study aimed to determine the recurrence rate and related risk factors of primary fallopian tube cancer (PFTC). Materials and Methods: We conducted a retrospective study of 47 patients with histopathological diagnosis of PFTC treated at Tu Du Hospital between January 1, 2015, and July 31, 2022. The cumulative recurrence rate was estimated using the life table method, and recurrence-associated factors were determined using the Log–rank test and Cox proportional hazard model. Results: The median follow-up period was 40 months (range, 7–96 months). Eight patients (17.0%) experienced recurrence. The cumulative recurrence rate of PFTC patients at 12 months was 4.4% (95% confidence interval [95% CI]: 1.12–16.45), at 24 months was 9.1% (95% CI: 3.52–22.5), at 36 months was 14.9% (95% CI: 6.92–30.41), at 48 months was 19.3% (95% CI: 9.35–37.24), and at 60 months was 25.7% (95% CI: 12.68–47.88). A higher recurrence rate was significantly associated with elevated pretreatment CA 125 level (<35 U/mL vs. ≥35 U/mL, hazards ratio [HR] = 36.9, 95% CI: 1.47–921.37), advanced FIGO stages (Stage I-II vs. stages III, HR = 6.61, 95% CI: 1.18–36.93), and suboptimal debulking surgery (residual disease ≤1 cm vs. residual disease >1 cm, HR = 7.52, 95% CI: 1.47–38.49). Conclusion: The overall recurrence rate of PFTC patients in Southern Vietnam was 17.0%. Appropriate follow-up strategies for patients with high-risk factors are needed for early detection and management of recurrence.

Radiomics combined with clinical and MRI features may provide preoperative evaluation of suboptimal debulking surgery for serous ovarian carcinoma.

To develop and validate a model for predicting suboptimal debulking surgery (SDS) of serous ovarian carcinoma (SOC) using radiomics method, clinical and MRI features. 228 patients eligible from institution A (randomly divided into the training and internal validation cohorts) and 45 patients from institution B (external validation cohort) were collected and retrospectively analyzed. All patients underwent abdominal pelvic enhanced MRI scan, including T2-weighted imaging fat-suppressed fast spin-echo (T2FSE), T1-weighteddual-echomagnetic resonanceimaging (T1DEI), diffusion weighted imaging (DWI), and T1 with contrast enhancement (T1CE). We extracted, selected and eliminated highly correlated radiomic features for each sequence. Then, Radiomic models were made by each single sequence, dual-sequence (T1CE + T2FSE), and all-sequence, respectively. Univariate and multivariate analyses were performed to screen the clinical and MRI independent predictors. The radiomic model with the highest area under the curve (AUC) was used to combine the independent predictors as a combined model. The optimal radiomic model was based on dual sequences (T2FSE + T1CE) among the five radiomic models (AUC = 0.720, P < 0.05). Serum carbohydrate antigen 125, the relationship between sigmoid colon/rectum and ovarian mass or mass implanted in Douglas' pouch, diaphragm nodules, and peritoneum/mesentery nodules were considered independent predictors. The AUC of the radiomic-clinical-radiological model was higher than either the optimal radiomic model or the clinical-radiological model in the training cohort (AUC = 0.908 vs. 0.720/0.854). The radiomic-clinical-radiological model has an overall algorithm reproducibility and may help create individualized treatment programs and improve the prognosis of patients with SOC.

Developing a novel image marker to predict the clinical outcome of neoadjuvant chemotherapy (NACT) for ovarian cancer patients

ObjectiveNeoadjuvant chemotherapy (NACT) is one kind of treatment for advanced stage ovarian cancer patients. However, due to the nature of tumor heterogeneity, the clinical outcomes to NACT vary significantly among different subgroups. Partial responses to NACT may lead to suboptimal debulking surgery, which will result in adverse prognosis. To address this clinical challenge, the purpose of this study is to develop a novel image marker to achieve high accuracy prognosis prediction of NACT at an early stage. MethodsFor this purpose, we first computed a total of 1373 radiomics features to quantify the tumor characteristics, which can be grouped into three categories: geometric, intensity, and texture features. Second, all these features were optimized by principal component analysis algorithm to generate a compact and informative feature cluster. This cluster was used as input for developing and optimizing support vector machine (SVM) based classifiers, which indicated the likelihood of receiving suboptimal cytoreduction after the NACT treatment. Two different kernels for SVM algorithm were explored and compared. A total of 42 ovarian cancer cases were retrospectively collected to validate the scheme. A nested leave-one-out cross-validation framework was adopted for model performance assessment. ResultsThe results demonstrated that the model with a Gaussian radial basis function kernel SVM yielded an AUC (area under the ROC [receiver characteristic operation] curve) of 0.806 ± 0.078. Meanwhile, this model achieved overall accuracy (ACC) of 83.3%, positive predictive value (PPV) of 81.8%, and negative predictive value (NPV) of 83.9%. ConclusionThis study provides meaningful information for the development of radiomics based image markers in NACT treatment outcome prediction.

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.

Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis.

To evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM). We retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas. A total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800). Supradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC. ClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1).

A prediction nomogram for suboptimal debulking surgery in patients with serous ovarian carcinoma based on MRI T1 dual-echo imaging and diffusion-weighted imaging

BackgroundSerous ovarian carcinoma (SOC) has the highest morbidity and mortality among ovarian carcinoma. Accurate identification of the probability of suboptimal debulking surgery (SDS) is critical. This study aimed to develop a preoperative prediction nomogram of SDS for patients with SOC.MethodsA prediction model was established including 205 patients of SOC from institution A, and 45 patients from institution B were enrolled for external validation. Multivariate logistic regression was used to screen independent predictors and establish a nomogram to predict the occurrence of SDS.ResultsMultivariate logistic regression demonstrated that the CA-125 level (odds ratio [OR] 8.260, 95% confidence interval [CI] 2.003–43.372), relationship between the sigmoid colon/rectum and ovarian mass (OR 28.701, 95% CI 4.561–286.070), diaphragmatic metastasis (OR 12.369, 95% CI 1.675–274.063), and FIGO stage (OR 32.990, 95% CI 6.623–274.509) were independent predictors for SDS. The area under the curve, concordance index, and 95% CI of the nomogram constructed from the above four factors were 0.951, 0.934, and 0.919–0.982, respectively. The model showed a good fit by the Hosmer–Lemeshow test (training set, p = 0.2475; internal validation set, p = 0.2355; external validation set, p = 0.2707). The external validation proved the reliability of the prediction nomogram. The calibration curve was close to the ideal diagonal line. The decision curve analysis demonstrated a significantly better net benefit. The clinical impact curve indicated good effectiveness in clinical application.ConclusionA prediction nomogram for SDS in patients with SOC provides gynecologists with an accurate and effective tool for appropriate management.

Overall Survival and Related Factors of Advanced-stage Epithelial Ovarian Cancer Patients Underwent Debulking Surgery in Jakarta, Indonesia: A Single-center Experience

AIM: The worrisome prognosis of advanced-stage epithelial ovarian cancer (EOC) needs a new perspective from developing countries. Thus, we attempted to study the 5-year overall survival (OS) of advanced-stage EOC patients who underwent debulking surgery in an Indonesian tertiary hospital. METHODS: A retrospective study recruited forty-eight subjects between 2013 and 2015. We conducted multiple logistic regression analyses to predict risk factors leading to unwanted disease outcomes. The OS was evaluated through the Kaplan–Meier curve and Log-rank test. Cox proportional hazards regression examined prognostic factors of patients. RESULTS: Prominent characteristics of our patients were middle age (mean: 51.9 ± 8.9 years), obese, with normal menarche onset, multiparous, not using contraception, premenopausal, with serous EOC, and FIGO stage IIIC. The subjects mainly underwent primary debulking surgery (66.8%), with 47.9% of all individuals acquiring optimal results, 77.1% of patients treated had the residual disease (RD), and 52.1% got adjuvant chemotherapy. The risk factor for serous EOC was menopause (odds ratio [OR] = 4.82). The predictors of suboptimal surgery were serous EOC (OR = 8.25) and FIGO stage IV (OR = 11.13). The different OS and median survival were observed exclusively in RD, making it an independent prognostic factor (hazard ratio = 3.50). 5-year A five year OS and median survival for patients with advanced-stage EOC who underwent debulking surgery was 37.5% and 32 months, respectively. Optimal versus suboptimal debulking surgery yielded OS 43.5% versus 32% and median survival of 39 versus 29 months. Both optimal and suboptimal debulking surgery followed with chemotherapy demonstrated an OS 40% lower than those not administered (46.2% and 20%, respectively). The highest 5-year OS was in serous EOC (50%). Meanwhile, the most extended median survival was with mucinous EOC (45 months). CONCLUSION: Chemotherapy following optimal and suboptimal debulking surgery has the best OS among approaches researched in this study. RD is a significant prognostic factor among advanced-stage EOC. Suboptimal surgery outcomes can be predicted by stage and histological subtype.

Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients.

Dickkopf-1 (DKK1) is a secreted protein, known for suppressing the differentiation and activity of bone-building osteoblasts by acting as an inhibitor of Wnt-signalling. Soluble DKK1 (sDKK1) has been proposed as prognostic biomarker for a wide range of malignancies, however, clinical relevance of sDKK1 as potential blood-based marker for ovarian cancer is unknown. sDKK1 levels were quantified in a cohort of 150 clinically documented ovarian cancer patients by a commercially available DKK1 ELISA (Biomedica, Vienna, Austria). Median sDKK1 level was significantly elevated at primary diagnosis of ovarian cancer compared to healthy controls (estimated difference (ED) of 7.75ng/mL (95% CI: 3.01-12.30ng/mL, p=0.001)). Higher levels of sDKK1 at diagnosis indicated an increased volume of intraoperative malignant ascites (ED 7.08pmol/L, 95% CI: 1.46-13.05, p=0.02) and predicted suboptimal debulking surgery (ED 6.88pmol/L, 95% CI: 1.73-11.87, p=0.01). sDKK1 did not correlate with CA125 and higher sDKK1 levels predicted a higher risk of recurrence and poor survival (PFS: HR=0.507, 95% CI: 0.317-0.809; p=0.004; OS: HR=0.561, 95% CI: 0.320-0.986; p=0.044). Prognostic relevance of sDKK1 was partly sustained in wtBRCA patients (PFS: HR=0.507, 95% CI: 0.317-0.809; p=0.004). This is the first study demonstrating the prognostic relevance of sDKK1 in ovarian cancer patients, including those with wtBRCA1/2 status. Our data encourage further evaluation of sDKK1 in ovarian cancer patients, possibly in terms of a therapy monitoring marker or a response predictor for sDKK1-directed targeted therapies.

Intrinsic STING expression inversely associates with survival in ovarian cancer patients

<h3>Objectives:</h3> The DNA sensing cGAS-STING signaling pathway plays a dual role of anti-tumor immunity and tumorigenesis. Chemoradiotherapy and PARPi induce DNA damage leading to activation of the cGAS-STING pathway, robust anti-tumor responses and improved clinical outcomes. Chronic activation of STING signaling creates an immunosuppressive TME and promotes metastases. Studies show that ovarian cancer cells have defective STING signaling. Current therapeutic strategies are focused on harnessing the beneficial effects of PARPi, IC blockade and STING agonists. However, the role for intrinsic ovarian tumor cGAS-STING levels in treatment responses and patient survival is unknown. The goal of this study is to determine the effect of tumor-specific cGAS-STING expression on survival in ovarian cancer patients. <h3>Methods:</h3> Using the Roswell Park Cancer Registry (RPCR), TMAs were generated from 488 patients treated for ovarian, fallopian tube or primary peritoneal cancer from 1991-2012. TMAs were stained for cGAS, STING and CD8 by IHC. cGAS and STING were scored based on the staining intensity (0-3) and the percent of positive cells (0-3) with a maximum combined score of 6 (0=no expression, 6=strong staining in >50% of cells). Additionally, the OS, PFS and cGAS-STING expression in 558 ovarian cancer patients from TCGA were analyzed. Clinico-pathologic data (age, demographics, histopathology, stage, tumor grade, treatment response, recurrence and survival) were retrieved from the electronic health records. <h3>Results:</h3> TCGA ovarian cancer patients with tumors expressing cGAShighSTINGhigh compared to cGASlowSTINGlow had OS of 38.4 months vs. 31.18 months (p=0.05). There was a significant positive correlation between gene and protein expression for cGAS (r=0.39, p=0.01) and STING (r=0.62, p<0.0001). Of the 488 patients in the RPCR, 95.3% were Caucasian with a median age at diagnosis of 63 years (range 20-93) and a median follow up of 44 months (range 0-279). The majority were diagnosed at an advanced surgical stage (68% and 14% at stage III and IV respectively), serous histology in 72% and high grade in 90.6% of cases. 72% received optimal and 27% had suboptimal debulking surgery. All patients received adjuvant platinum and taxane chemotherapy and the initial recurrence rate was 52%. In addition, 42.2% were platinum sensitive, 30% were refractory and 18% were platinum resistant. During the first 60 months of follow up, there was a trend toward improved OS and PFS in patients with cGASlowSTINGlow compared to cGAShighSTINGhigh tumors. Independently, cGAS did not associate with OS or PFS. Interestingly, STING high tumors correlated positively with CD8+ TILs (r=0.05, p=0.0002) but associated with decreased PFS (p=0.016). <h3>Conclusions:</h3> TCGA dataset revealed cGAShighSTINGhigh expressing tumors correlated with improved OS. By contrast, high grade ovarian tumors with intrinsically high levels of STING correlate with increased CD8+ TILs and decreased PFS.

Prediction of optimal debulking surgery in ovarian cancer.

The mainstay management of advanced ovarian cancer is maximal cytoreductive surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) are alternative treatments for patients with comorbidity, poor performance status, and predicted for suboptimal debulking surgery. It is the invariable principle in any situation that no residual disease after the completion of surgery is useful for patients with ovarian cancer. Therefore, the prediction of optimal debulking before the treatment of ovarian cancer is of utmost importance. Many studies have reported on the use of serum biomarkers, such as cancer antigen 125 (CA125) or human epididymis 4 (HE4), and imaging studies, such as computed tomography (CT), diffusion-weighted magnetic resonance imaging (DW-MRI), and positron emission tomography (PET)/CT, to identify adequate surgical candidates for primary debulking surgery (PDS). Laparoscopy has also been studied as a reliable tool for the prediction of optimal debulking. Here, we summarize a review of the related literature.

Higher Level of Fatty Acid Synthase Enzyme Predicts Lower Rate of Completing Debulking Surgery in Epithelial Ovarian Cancer.

Background:The most dominant histopathologic type of ovarian cancer is epithelial ovarian cancer (EOC). Primary debulking surgery determines the treatment success and prognosis of advanced stage EOC. To maintain survival and progression, cancer cells need fatty acid synthase enzyme (FASN). The aim of this study was to evaluate preoperative serum FASN and CA 125 as predictors of primary debulking surgery results in patients with EOC. Methods:An observational cross-sectional study was performed on consecutive patients who underwent debulking surgery for suspected ovarian cancer at Dr. Hasan Sadikin Hospital Bandung from 2017 to 2019. Before debulking surgery, blood samples were examined for the serum levels of FASN and CA 125 using ELISA.Results:There were 53 patients enrolled in this study. Compared with the optimal debulking surgery group, the significant suboptimal debulking surgery group had significantly lower mean serum levels of FASN (0.46 ± 0.144 vs. 0.36 ± 0.128, p = 0.012) and CA 125 (964.22 ± 1722.5 vs. 264.98 ± 251.8, p = 0.002). The cutoff value was highest for the combination of FASN and CA 125 [410.06, area under the curve (AUC) = 77.5% (95% CI 65.5% to 81.9%, p = 0.001)] than for FASN alone [0.375, AUC = 71.3% (95% CI 56.8% to 85.8%, p = 0.009)] and CA 125 alone [222.5, AUC = 75.3% (95% CI 62.5% to 88.1%, p =0.002)]. Conclusion:The serum levelof FASN was correlated with suboptimal debulking surgery.

Risk predictors of early recurrence in women with epithelial ovarian cancer in Lagos, Nigeria.

Introductionepithelial ovarian cancer (EOC) is the most lethal gynaecological cancer with a recurrence rate as high as 85% after an initial treatment. However, there are currently no reliable means of predicting the risk of recurrence after first-line treatment. This study investigated the risk factors that predict early recurrence of EOC after primary treatment among women in Lagos, Nigeria.Methodsthis was a retrospective cohort study involving the review of all histologically confirmed EOC patients managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. A study proforma was used to retrieve relevant information and descriptive statistics were computed for all data. The associations between variables were tested and multivariate analysis was done to adjust for all the possible characteristics that predict early EOC recurrence.Resultsthe rate of recurrence of EOC was 76.4%. Suboptimal debulking surgery is the only independent predictor of early tumour recurrence.Conclusionwomen should be adequately counselled and encouraged to report their symptoms early to ensure optimal primary treatment. Strategic efforts should also be made to further improve subspecialty training programs and skills development in gynaecological oncology in Nigeria and sub-Saharan Africa.

Serum calretinin as a predictor for recurrence and overall survival in ovarian cancer.

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p &lt; 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p &lt; 0.001) and were associated with advanced FIGO-stage (p &lt; 0.001) and high volume of ascites (p &lt; 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.

Laparoscopy for diagnosing resectability of disease in women with advanced ovarian cancer.

This is an update of a Cochrane Review that was originally published in 2014, Issue 2.The presence of residual disease after primary debulking surgery is a highly significant prognostic factor in women with advanced ovarian cancer. In up to 60% of women, residual tumour of > 1 cm is left behind after primary debulking surgery (defined as suboptimal debulking). These women might have benefited from neoadjuvant chemotherapy (NACT) prior to interval debulking surgery instead of primary debulking surgery followed by chemotherapy. It is therefore important to select accurately those women who would best be treated with primary debulking surgery followed by chemotherapy from those who would benefit from NACT prior to surgery. To determine if performing a laparoscopy, in addition to conventional diagnostic work-up, in women suspected of advanced ovarian cancer is accurate in predicting the resectability of disease. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE via Ovid, Embase via Ovid, MEDION and Science Citation Index and Conference Proceedings Citation Index (ISI Web of Science) to July 2018. We also checked references of identified primary studies and review articles. We included studies that evaluated the diagnostic accuracy of laparoscopy to determine the resectability of disease in women who are suspected of advanced ovarian cancer and planned to receive primary debulking surgery. Pairs of review authors independently assessed the quality of included studies using QUADAS-2 and extracted data on study and participant characteristics, index test, target condition and reference standard. We extracted data for two-by-two tables and summarised these graphically. We calculated sensitivity and specificity and negative predictive values. We included 18 studies, reporting on 14 cohorts of women (including 1563 participants), of which one was a randomised controlled trial (RCT). Laparoscopic assessment suggested that disease was suitable for optimal debulking surgery (no macroscopic residual disease or residual disease < 1 cm (negative predictive values)) in 54% to 96% of women who had macroscopic complete debulking surgery (no visible disease at end of laparotomy) and in 69% to 100% of women who had optimal debulking surgery (residual tumour < 1 cm at end of laparotomy).Only two studies avoided partial verification bias by operating on all women independent of laparoscopic findings, and provided data to calculate sensitivity and specificity. These two studies had no false positive laparoscopies (i.e. no women had a laparoscopy indicating unresectable disease and then went on to have optimal debulking surgery (no disease > 1 cm remaining)).Due to the large heterogeneity pooling of the data was not possible for meta-analysis. Laparoscopy may be a useful tool to identify those women who have unresectable disease, as no women were inappropriately unexplored. However, some women had suboptimal primary debulking surgery, despite laparoscopy predicting optimal debulking and data are at high risk of verification bias as only two studies performed the reference standard (debulking laparotomy) in test (laparoscopy)-positive women. Using a prediction model does not increase the sensitivity and will result in more unnecessarily explored women, due to a lower specificity.

A study of clinicopathologic factors as indicators for early prediction of suboptimal debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer.

This study aimed to evaluate early clinicopathologic factors predicting gross residual disease after neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. We analyzed clinicopathologic data of 68 patients with ovarian cancer who were treated with neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) between March 2006 and December 2016. All the patients received three cycles of NAC followed IDS. We evaluated all possible clinicopathologic characteristics, including reduction rates of serum CA-125 after each NAC and seven initial abdominopelvic computed tomography (CT) findings related to disease severity. After IDS, no gross residual disease was found in 46 (67.6%) patients and 22 (33.4%) patients had gross residual disease. Multivariate analysis identified that reduction rate of CA-125 after 2nd NAC, body mass index (BMI) and small bowel lesion in the initial CT findings were significantly associated with gross residual disease after IDS (P = 0.005, 0.030, 0.001, respectively). The optimal cutoff value predicting gross residual disease were less than 50% of CA-125 reduction rate after 2nd NAC and low BMI (<23 kg/m2 ). The combined receiver operating characteristic curve analysis of these factors showed good performance for predicting gross residual disease after IDS (area under the curve = 0.845). A model using small bowel mesentery involvement on CT, BMI (<23 kg/m2 ) and less than 50% reduction of the initial CA-125 level after the 2nd NAC is highly predictive of gross residual disease after IDS in advanced ovarian cancer patients. These results may be helpful in further treatment planning and patients counseling.

Optimizing the treatment of ovarian cancer: Neoadjuvant chemotherapy and interval debulking versus primary debulking surgery for epithelial ovarian cancers likely to have suboptimal resection

ObjectiveTo: a) identify prognostic factors in patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS), and b) compare post-surgical survival between patients treated with NACT/IDS for presumed unresectable disease and stage IIIC/IV patients who underwent suboptimal primary debulking surgery (PDS). MethodsThis was a retrospective study of consecutive stage IIIC or IV patients undergoing IDS after NACT at Mayo Clinic from January 2007 to December 2013. A subset of patients receiving NACT/IDS for the indication of unresectable disease were matched 1:1 on age and stage to a cohort of patients who underwent suboptimal PDS between 2003 and 2011. Hazard ratios and corresponding 95% confidence intervals were estimated from Cox proportional hazards models. ResultsWe identified 87 patients treated with NACT/IDS: the median OS and PFS following surgery was 2.4 and 1.0years, respectively. Factors associated with significantly worse OS were older age (adjusted HR 1.60 per 10-year increase in age, 95% CI 1.18, 2.16) and elevated CA-125 before IDS (adjusted HR 2.30 for CA-125 >35U/mL, 95% CI 1.25, 4.23). Number of adjuvant chemotherapy cycles administered did not have a significant effect on survival. In the matched cohort analysis of presumed unresectable cases undergoing NACT/IDS vs suboptimal PDS cases (n=45 each), the NACT/IDS group had a significant OS advantage (HR 0.53; 95% CI 0.32, 0.88), and fewer patients experienced a 30-day postoperative Accordion grade 3/4 complication (11% vs 36%, P=0.01). ConclusionsYounger age and normalization of CA-125 prior to IDS are associated with improved survival with NACT/IDS. For primary EOC where resection to residual disease of 1cm or less is unlikely, NACT/IDS is associated with improved survival and reduced perioperative morbidity compared to PDS. As these patients are likely best served by NACT/IDS, more reliable predictors of resectability would be valuable.

Neoadjuvant chemotherapy is superior to primary debulking surgery in patients with presumed unresectable epithelial ovarian cancer

Objectives: We sought to: (1) identify prognostic factors in epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS), and (2) compare overall (OS) and progression-free survival (PFS) between NACT for presumed unresectable disease versus suboptimal primary debulking surgery (PDS). Methods: This was a retrospective study of consecutive patients undergoing IDS after NACT at our institution from 2007 to 2013. Clinical factors were abstracted from medical records and complete clinical response (CCR) was defined as no gross disease at IDS. Survival times were estimated with the Kaplan-Meier method and compared using the log-rank test. The subset of patients receiving NACT for the indication of presumed unresectable disease were matched 1:1 on age and stage with a contemporary cohort of patients receiving suboptimal PDS between 2003 and 2011. Survival times were compared using stratified Cox models to account for the varying duration of follow-up within each matched pair. Results: Eighty-eight patients were treated with NACT/IDS, and median PFS and OS were 1.3 and 2.6 years, respectively. The following factors were associated with improved survival after NACT: normalization of CA-125 before IDS (median OS 3.0 vs 1.9 years, P = .02); age less than 65 (3.3 vs 1.9 years, P = .005); CCR at IDS (5.6 vs 2.5 years, P = .15), and no gross residual disease after IDS (2.9 vs 2.2 years, P = .06). We saw no association between survival and number of post-IDS chemotherapy cycles, 3 vs more than 3 cycles, including among those with persistently elevated CA-125 at IDS (median OS 2.2 vs 2.7 years, P = 0.63). In our matched comparison of unresectable cases treated with NACT versus suboptimal PDS, we observed a significant OS advantage for NACT (HR 0.46, 95% CI 0.23–0.92), with no significant difference in PFS. Conclusions: We saw no survival benefit with increasing duration of adjuvant chemotherapy after IDS, but selection bias likely minimizes the benefit in partial responders. Young age, clinical response, and residual disease are all likely predictors of OS. For primary EOC in which resection to residual disease less than 1 cm is unlikely, NACT is associated with longer survival than PDS. Analysis of morbidity and costs are ongoing. As these patients are likely best served by NACT, more reliable predictors of resectability are needed to better identify such cases.

Primary peritoneal serous papillary carcinoma that metastasized to an axillary lymph node in a woman with a history of breast cancer: A case report and diagnostic pitfalls

Herein, we will report on a patient with primary peritoneal serous papillary carcinoma that metastasized to an axillary lymph node and who had previously undergone a mastectomy and chemotherapy for carcinoma of the right breast. A 40-year-old Japanese woman underwent partial resection of her left lung for metastatic breast cancer at our hospital. Thirteen years later, she developed a left axillary lymph node swelling, and a biopsy was performed. Histological findings were compatible with metastatic breast carcinoma. Positron emission tomography–computed tomography revealed systemic lymphadenopathy, peritoneal nodules, and a liver mass. The patient was diagnosed with recurrent breast cancer and underwent additional chemotherapy. Six months later, she developed ascites. She was diagnosed with serous adenocarcinoma using conventional and immunocytological examinations of the ascites. She underwent suboptimal debulking surgery, consisting of a total hysterectomy, bilateral oophorectomy, and partial omentectomy. The final pathological diagnosis was primary peritoneal serous papillary carcinoma.The diagnosis and pitfalls of this case will be presented.

Locally-advanced unresected uterine leiomyosarcoma with triple-modality treatment combining radiotherapy, chemotherapy and hyperthermia: A case report

Advanced uterine leiomyosarcoma (LMS) is a rare and extremely aggressive disease. In patients with advanced and unresected uterine LMS, multidisciplinary therapy is the best treatment option, although no consensus exists on the efficacy of the treatment. The present study describes the case of a 41-year-old female who underwent laparotomy due to a large uterine tumor. Exploratory laparotomy revealed a large tumor that had extended from the pelvic wall to the outside of the pelvis and then invaded the colon. Large residual tumors remained present in the pelvis following suboptimal debulking surgery. Subsequent to surgery, the patient was treated with adjuvant radiotherapy, followed by chemotherapy with regional whole pelvis hyperthermia (HT). Computed tomography revealed stable disease prior and subsequent to combination treatment. While treatment was being administered for third/fourth-degree burns and subcutaneous fatty necrosis, the patient developed multi-organ failure and succumbed. The present case report describes the potential for using a combination of chemotherapy, HT and radiotherapy in patients with LMS. The development of an effective protocol is required for the administration of chemotherapy, HT and radiotherapy in patients with advanced unresected LMS.

The association between neighborhood socioeconomic status and ovarian cancer tumor characteristics

Higher pathologic grade, suboptimal debulking surgery, and late-stage are markers of more aggressive and advanced ovarian cancer. Neighborhood socioeconomic status (SES) has been associated with more aggressive and advanced tumors for other cancer sites, and this may also be true for ovarian cancer. We examined the association between neighborhood SES and ovarian cancer tumor characteristics using data on 581 women diagnosed with epithelial ovarian cancer in Cook County, Illinois. Two complementary measures (concentrated disadvantage and concentrated affluence) were used to estimate neighborhood SES. Prevalence differences and 95 % confidence intervals were estimated in logistic regression models adjusted for age and race. Greater disadvantage was associated with higher grade tumors (p = 0.03) and suboptimal debulking (p = 0.05) and marginally associated with later tumor stage (p = 0.20). Greater affluence was inversely associated with stage at diagnosis (p = 0.004) and suboptimal debulking (p = 0.03) and (marginally) with tumor grade (p = 0.21). Our findings suggest that lower SES, estimated by neighborhood SES, is associated with ovarian cancer tumor characteristics indicative of more advanced and aggressive disease.