Cell-free tumor DNA, CA125 and HE4 for the objective assessment of tumor burden in patients with advanced high-grade serous ovarian cancer.

BACKGROUND: The present prospective study aimed at determining the impact of cell-free tumor DNA (ct-DNA), CA125 and HE4 from blood and ascites for quantification of tumor burden in patients with advanced high-grade serous epithelial ovarian cancer (EOC). METHODS: Genomic DNA was extracted from tumor FFPE and ct-DNA from plasma before surgery and on subsequent post-surgical days. Extracted DNA was subjected to hybrid-capture based next generation sequencing. Blood and ascites were sampled before surgery and on subsequent post-surgical days. 20 patients (10 undergoing complete resection (TR0), 10 undergoing incomplete resection (TR>0)) were included. RESULTS: The minor allele frequency (MAF) of TP53 mutations in ct-DNA of all patients with TR0 decreased significantly, compared to only one patient with TR>0. It was not possible to distinguish between patients with TR0 and patients with TR>0, using CA125 and HE4 from blood and ascites. CONCLUSIONS: Based upon the present findings, ct-DNA assessment in patients with high-grade serous EOC might help to better determine disease burden compared to standard tumor markers. Further studies should prospectively evaluate whether this enhancement of accuracy can help to optimize management of patients with EOC.

Validation analysis of the novel imaging-based prognostic radiomic signature in patients undergoing primary surgery for advanced high-grade serous ovarian cancer (HGSOC).

BACKGROUND: Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality. METHODS: RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models. RESULTS: The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06-2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56-2.62; P = 0.00647). CONCLUSIONS: RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine.

Current Status of Metastatic Cardiophrenic Lymph Nodes (CPLNs) in Patients With Ovarian Cancer: A Review.

BACKGROUND: One of the most common sites of extra-abdominal disease spread of advanced stage ovarian cancer is the cardiophrenic lymph node (CPLN) region. The role and impact of extra-abdominal cytoreduction is not obvious in patients with cardiophrenic lymph node metastases. MATERIALS AND METHODS: We examined the relevant and currently available literature to determine the prognostic value and management of enlarged CPLNs in ovarian cancer patients. RESULTS: Transdiaphragmatic excision of CPLNs or via video-assisted thoracoscopic surgery (VATS) is achievable without major complications. The most common postoperative complications were pleural effusion, pneumothorax and pneumonia. On preoperative CT scan, the cut-off size of suspicious CPLNs is not uniform and is indicated as 5 to 10 mm short-axis dimension. CONCLUSION: CPLNs were detected in up to 60% of patients and malignancy was pathologically confirmed in 45-95% of the cases. The presence of enlarged CPLNs was found to be a negative prognostic factor, although its impact on progression-free and overall survival is not yet clarified and needs further investigation.

Modern day screening for Lynch syndrome in endometrial cancer: the KEM experience.

PURPOSE: Current guidelines for Lynch syndrome detection in endometrial cancer (EC) patients rely either on risk evaluation, based on personal/family history, or detection of mismatch repair (MMR) deficiency on tumor tissue. We present a combined screening algorithm for Lynch syndrome. METHODS: In this study, 213 consecutive patients treated for EC at Kliniken Essen-Mitte between 2014 and 2018 were included. Personal/family history was evaluated by the Amsterdam II, revised Bethesda/German-DKG criteria and prediction model PREMM5. MMR testing was performed by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) based microsatellite analysis on tumor tissue. MLH1 promoter methylation analysis was performed in case of MLH1 loss or microsatellite instability. RESULTS: Based on personal/family history 2/213 (Amsterdam II), 31/213 (revised Bethesda/German-DKG) and 149/213 (PREMM5) patients were identified as at risk for Lynch syndrome. MMR analysis was performed by IHC in 51.2%, by PCR in 32.4%, and in 16.4% of patients both methods were used. MMR deficiency was detected in 20.6% (44/213). Methylation analysis was performed in 27 patients of whom, 22 (81.4%) showed MLH1 promoter hypermethylation. Only 9% of MMR deficient patients were identified as at risk for Lynch syndrome by the revised Bethesda/German-DKG criteria. A pathogenic germline mutation was discovered in 3 out of 20 patients that underwent genetic testing. None of these patients were younger than 50 years or had a family history of Lynch syndrome-associated malignancies. CONCLUSION: General MMR assessment is a feasible strategy to improve the detection of Lynch Syndrome in patients with EC.

Cell-Free-DNA-Based Copy Number Index Score in Epithelial Ovarian Cancer-Impact for Diagnosis and Treatment Monitoring.

BACKGROUND: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment. METHODS: Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set. RESULTS: Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively. CONCLUSION: ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor.

Dataset on patients with Recurrent Borderline Ovarian Tumors and Table with Review of Literature on Fertility and Oncologic Outcomes of patients with Borderline Ovarian Tumors.

The data presented here is related to the research article entitled "FERTILITY-SPARING SURGERY AND REPRODUCTIVE-OUTCOMES IN PATIENTS WITH BORDERLINE OVARIAN TUMORS" by Plett et al. in Journal of Gynecologic Oncology [1] and is analysed and discussed in detail. 18 Patients with Recurrent Borderline Ovarian Tumors (BOT) were identified and listed in Table 1. All patients underwent treatment for primary BOT either per radical surgery (RS) or fertility sparing surgery (FSS) by the same team in Horst Schmidt Klinik (HSK) in Wiesbaden and the Department of Gynecology and Gynecologic Oncology at Kliniken Essen-Mitte between January 2000 and December 2018 and were followed up closely. Details on patients` and surgical characteristics are given as well as management of character of recurrent disease. In Table 2 important publications from the last 20 years are listed in order to visualize better the oncologic outcomes (invasive and non-invasive relapses) and calculated risks of recurrence with the purpose to understand better the important findings of the related article cited above.

Fertility-sparing surgery and reproductive-outcomes in patients with borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors (BOT) are considered a biological category with increased epithelial proliferation and cellular atypia in the absence of invasive growth. Since BOT occur often in young patients fertility sparing surgery (FSS) is an important issue. With this study we aimed to evaluate risk factors for relapses and fertility of patients after FSS. METHODS: Patients diagnosed with BOT and treated between 2000 and 2018 were included. External pathological review was done in all patients. FSS was performed after individual discussion and a complete surgical staging according to FIGO, without lymphadenectomy and with a waiver for preservation of uterus and one ovary. RESULTS: Among 352 Patients 80.2% had FIGO I and 63.9% had a serous BOT. Eighteen patients (5.1%) relapsed and 4 cases of malignant transformation were reported (1.1%). One patient of the latter died, all others have no evidence of disease. The overall recurrence-rate was 1.1% in FIGO-Stage I and 25.5% in FIGO III-IV (HR = 27; 95%-CI 7.7-95; p ≤.001). 95 patients underwent FSS. Thirteen (13.7%) of these patients relapsed, all as BOT. In multivariate analysis FIGO stages II-IV (HR = 27; 95%-CI: 8.1-102; p ≤.001) and FSS (HR = 12; 95%-CI: 2.9-47; p = .001) remained significant risk factors for recurrent disease. Pregnancy rate among forty-one patients attempting to conceive was 82.9%. 29 patients experienced at least one life-birth, in total 38 life-births were reported. CONCLUSION: FSS in stage I is a safe procedure and life-birth-rates after FSS are high. More advanced FIGO stages have to be discussed individually and relapse rates have to be weighed against FSS. A central review of pathology, as we performed routinely, is mandatory and may have contributed to our low rate of invasive relapses.

Sentinel lymph node mapping with fluorescent and radioactive tracers in vulvar cancer patients.

PURPOSE: Application of radioactive tracers for sentinel lymph node biopsy (SLNB) in vulvar cancer has been established, however, the use of radioisotopes is expensive and requires complex logistics. This exploratory study evaluated the feasibility of near-infrared fluorescence-based SLNB in comparison to the gold standard using radioactive guidance. METHODS: At Evangelische Kliniken Essen-Mitte (Essen, Germany) between 02/2015 and 04/2019, 33 patients with squamous cell vulvar cancer and unifocal tumors (32 midline, 1 lateral) smaller than 4 cm underwent SLNB as part of their routine primary surgical therapy. Radiolabeled nanocolloid technetium 99 (99mTc) was injected preoperatively and indocyanine green (ICG) intraoperatively. Demographic and clinical data were retrieved from patients' records, and descriptive statistics were applied. The detection rate of the ICG fluorescence technique was compared with the standard radioactive approach. RESULTS: In patients with midline tumors, bilateral SLNB was attempted. SLNB was feasible in 61/64 (95.3%) groins with 99mTc and in 56/64 (87.5%) with ICG. In total, 125 SLNs were excised; all SLNs were radioactive and 117 (93.6%) also fluorescent. In 8 patients with BMI > 30 kg/m2, SLNB was successful in 14/15 groins (93.3%) with 99mTc and 13/15 groins (86.7%) with ICG. Upon final histology, infiltrated nodes were present in 9/64 (14.1%) groins and 10/125 SLNs; one positive SLN was not detected with ICG. CONCLUSIONS: SLNB using ICG is a promising technique, however, the detection rate obtained was slightly lower than with 99mTc. The detection rate increased over time indicating that experience and training may play an important role besides further methodological refinements.

Low-grade Serous Tumors: Are We Making Progress?

PURPOSE OF REVIEW: This review provides an overview of the current clinical standard in low-grade serous ovarian cancer (LGSOC). The available evidence for surgery and standard treatments is elaborated. In addition, we discuss recent findings and novel treatments for LGSOC. RECENT FINDINGS: Two large multicenter trials studying MEK inhibitors in LGSOC have been presented in the last year. Binimetinib demonstrated an activity in LGSOC, especially in KRAS-mutated disease. Trametinib was associated with an improved progression-free survival in relapsed LGSOC. Based on the current results, MEK inhibitors could be an alternative treatment for LGSOC. Surgery is an important step in the treatment of LGSOC. Hormonal therapy and bevacizumab can be beneficial, next to chemotherapy. Targeted treatments, such as the MEK-inhibitor trametinib, seem to be efficient and should be introduced into clinical practice.

Dilution of Molecular-Pathologic Gene Signatures by Medically Associated Factors Might Prevent Prediction of Resection Status After Debulking Surgery in Patients With Advanced Ovarian Cancer.

PURPOSE: Predicting surgical outcome could improve individualizing treatment strategies for patients with advanced ovarian cancer. It has been suggested earlier that gene expression signatures (GES) might harbor the potential to predict surgical outcome. EXPERIMENTAL DESIGN: Data derived from high-grade serous tumor tissue of FIGO stage IIIC/IV patients of AGO-OVAR11 trial were used to generate a transcriptome profiling. Previously identified molecular signatures were tested. A theoretical model was implemented to evaluate the impact of medically associated factors for residual disease (RD) on the performance of GES that predicts RD status. RESULTS: A total of 266 patients met inclusion criteria, of those, 39.1% underwent complete resection. Previously reported GES did not predict RD in this cohort. Similarly, The Cancer Genome Atlas molecular subtypes, an independent de novo signature and the total gene expression dataset using all 21,000 genes were not able to predict RD status. Medical reasons for RD were identified as potential limiting factors that impact the ability to use GES to predict RD. In a center with high complete resection rates, a GES which would perfectly predict tumor biological RD would have a performance of only AUC 0.83, due to reasons other than tumor biology. CONCLUSIONS: Previously identified GES cannot be generalized. Medically associated factors for RD may be the main obstacle to predict surgical outcome in an all-comer population of patients with advanced ovarian cancer. If biomarkers derived from tumor tissue are used to predict outcome of patients with cancer, selection bias should be focused on to prevent overestimation of the power of such a biomarker.See related commentary by Handley and Sood, p. 9.

Adult primary cervical rhabdomyosarcomas: A Multicentric cross-national case series.

OBJECTIVES: Adult primary cervical rhabdomyosarcoma is a very rare disease and data regarding treatment are sparce. The goal of this study was to report on our experience with the management of this rare entity, along with an evaluation of the literature. METHODS: We conducted a review of the medical records at four centers from January 1990 to December 2017. We reviewed clinical characteristics including age at diagnosis, BMI, medical history and tumor stage, as well as treatment in the primary and recurrent settings and follow-up data. We reclassified tumors according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group. RESULTS: A total of 15 patients were included in the analysis. Median age at diagnosis was 35 years (range 17-55). Median tumor size at presentation was 5 cm (range 3-10). Eleven patients had the embryonal variant, including five showing the botryoid subtype. Four patients had a pleomorphic rhabdomyosarcoma. Eleven patients had disease classified as IRS Clinical Group I, while the remaining four fell into groups II or III. Fertility-sparing treatment was offered to five patients. Primary treatment types were: surgery alone in eight patients, surgery followed by adjuvant chemotherapy in six patients, and neoadjuvant chemotherapy in two patients. The main risk factors for relapse were: IRS clinical group greater than I, tumor size greater than 5 cm, lymph nodal involvement, and non-embryonal histology. At a median follow-up of 35 months (range 3-282), we observed a 5-year overall survival rate of 78.2% and a progression-free survival of 58.2%. No patient in the IRS I group died of the disease. Three out of four patients in the IRS II-III group died of the disease (survival range 5-16 months following treatment). CONCLUSION: Our data show that cervical rhabdomyosarcomas account for at least two prognostic groups, demonstrating the existence of low-risk and high-risk patterns. The best predictor of prognosis appearsd to be the IRS clinical group classification system. IRS Group I tumors had an overall good prognosis and rarely recurred; when they did recur they were mainly local, following conservative treatment.

Perception of side effects associated with anticancer treatment in women with breast or ovarian cancer (KEM-GO-1): a prospective trial.

PURPOSE: Due to advances in anticancer treatment and supportive care, patients increasingly complained about nonphysical side effects of chemotherapy and targeted therapy in recent years. Therefore, continuous assessment of side effects and patients' perceptions is important. The aim of this study was to evaluate the identification and severity of side effects perceived by ovarian cancer (OC) and breast cancer (BC) patients undergoing contemporary anticancer therapy. METHODS: Between 2015 and 2017, consecutive chemo-naïve OC and BC patients were enrolled in this prospective cohort study. Interviews were performed 12 ± 3 weeks after start of anticancer therapy, and patients were asked to select and rank, according to severity, 72 physical or nonphysical symptoms potentially related to their treatment. Data were analyzed with descriptive statistics. RESULTS: Forty-five OC patients and 98 BC patients completed the interview. Sleeping difficulties were ranked as the most troublesome symptom, followed by concerns about family or partner, and loss of hair. Alopecia was the most predominant side effect for BC patients, whereas OC patients were highly afflicted by numbness in limbs. Chemotherapy alone or in combination with targeted therapy caused pronounced sleep disturbances. Prolonged taxane treatment led to shortness of breath and numbness in limbs. Vomiting was ranked by one and nausea by eight women among the five most bothersome symptoms. CONCLUSIONS: Sleep disturbances have lately emerged as the most severe problem in women with OC or BC receiving anticancer therapy. Concerns about family and partner were ranked second in the current study and first in previous investigations.

Low anterior resection syndrome (LARS) in patients with epithelial ovarian cancer after primary debulking surgery.

OBJECTIVE: To evaluate the prevalence of low anterior resection syndrome (LARS) in patients with debulking surgery for primary advanced epithelial ovarian cancer and to identify potential risk factors for development of LARS. METHODS: We reviewed data on 552 consecutive patients with primary epithelial ovarian cancer (EOC), who underwent upfront or interval cytoreductive surgery including low anterior resection at two different academic institutions (Kliniken-Essen-Mitte, Germany, and Medical University of Vienna, Austria). Intestinal dysfunction was assessed by the validated LARS-questionnaire via telephone call. We performed descriptive statistics and a binary logistic regression model to evaluate risk factors for LARS. RESULTS: In total, 341 patients were eligible and 206 (60.4%) were successfully contacted and provided complete information. Major LARS was observed in 78 (37.9%) patients, minor LARS in 44 (21.4%) patients, and no LARS in 84 (40.8%) patients. The prevalence rate of major LARS was not influenced by time interval between surgery and LARS assessment, type of cytoreductive surgery, and recurrent disease at the time of assessment. In multivariate analyses, number of anastomosis was independently associated with an increased risk for presence of major LARS (OR 3.76 [1.95-7.24]). In the present cohort, 25.2% patients had more than one bowel anastomosis. CONCLUSIONS: LARS in general and major LARS in particular seem to be a frequent long-term complication after debulking surgery including low anterior resection in primary advanced EOC patients. Particularly EOC patients with more than one bowel anastomosis during surgery seem to be at an increased risk for major LARS.

Pattern and impact of metastatic cardiophrenic lymph nodes in advanced epithelial ovarian cancer.

BACKGROUND: Cardiophrenic lymph nodes (CPLN) define FIGO stage IVB disease. We evaluate the pattern of CPLN metastases, their prognostic impact and the potential role of CPLN resection in patients with epithelial ovarian cancer (EOC). METHODS: Analysis of 595 consecutive patients with EOC treated in the period 01/2011-05/2016. CT scans were re-reviewed by two radiologists. Positive CPLN were defined as ≥5 mm in the short-axis diameter. The role of CPLN resection was evaluated in a case-control matched-pair analysis. RESULTS: Of 595 patients 458 had FIGO stage IIIB-IV disease. We excluded patients undergoing interval surgery (n = 54), without debulking surgery (n = 32) and without sufficient pre-operative imaging (n = 22), resulting in a study cohort of 350 patients. Of these, 133 (37.9%) had negative CPLN and 217 (62.0%) had radiologically positive CPLN. In patients with postoperative residual tumor, enlarged CPLN had no impact on survival. In patients with complete resection (n = 223), 98 (44.0%) had negative CPLN and a 5-year OS of 69% and a 5-year PFS of 41%; in contrast, in the 125 patients (56.0%) with positive CPLN, 5-year OS was 30% and 5-year PFS was 13%. In 52 patients we resected CPLN. The matched-pair case-control analysis did not demonstrate any significant impact on survival of CPLN resection. CONCLUSION: CPLN metastases are associated with impaired PFS and OS in patients with macroscopically completely resected tumor. Intraabdominal residual tumor has a greater prognostic impact than positive CPLN. The impact of the resection of CPLN remains unclear.

How to manage lymph nodes in ovarian cancer.

The indication for staging lymphadenectomy in patients with ovarian cancer (both early- and late-stage disease) has been a major topic of debate in the last decades. Because the Lymphadenectomy in Ovarian Neoplasms (LION) study has recently demonstrated that systematic lymphadenectomy is not beneficial to patients with advanced ovarian cancer, the discussion has become more complex for patients with early-stage ovarian cancer. Further factors, such as differences in the lymph node metastasis rates of different histologic subtypes, which were not known in the past, need to be taken into account. This review is focused on the available evidence concerning lymphadenectomy in patients with newly diagnosed ovarian cancer.

Low-grade Serous Ovarian Carcinoma.

In the early 2000s a two-tier grading system was introduced for serous ovarian cancer. Since then, we have increasingly come to accept that low-grade serous ovarian carcinoma (LGSOC) is a separate entity with a unique mutational landscape and clinical behaviour. As less than 10% of serous carcinomas of the ovary are low-grade, they are present in only a small number of patients in clinical trials for ovarian cancer. Therefore the current treatment of LGSOC is based on smaller trials, retrospective series, and subgroup analysis of large clinical trials on ovarian cancer. Surgery plays a major role in the treatment of patients with LGSOC. In the systemic treatment of LGSOC, hormonal treatment and targeted therapies seem to play an important role.

Skeletal Muscle Attenuation (Sarcopenia) Predicts Reduced Overall Survival in Patients with Advanced Epithelial Ovarian Cancer Undergoing Primary Debulking Surgery.

BACKGROUND: Sarcopenia was reported as a prognostic factor in cancer patients. Using computed tomography (CT), we analyzed the impact of sarcopenia on overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). METHODS: Preoperative CT scans of consecutive EOC patients (n = 323) were retrospectively assessed for skeletal muscle index (SMI) and muscle attenuation (MA; Hounsfield units [HU]). The optimal cut-off point for MA (32 HU) was calculated using the Martingale residuals method, and previously reported cut-offs for SMI were used. Logistic regression was used to determine univariate and multivariate factors associated with OS. RESULTS: Sarcopenia defined as SMI < 38.5, < 39, and 41 cm2/m2 was detected in 29.4, 33.7, and 47.1% of patients, respectively; however, none of these SMI cut-off levels were associated with OS. MA < 32 HU was present in 21.1% (68/323) of the total cohort. Significant differences between patients with MA < 32 and ≥ 32 HU were detected for median age (67 vs. 57 years), Eastern Cooperative Oncology Group (ECOG) > 0 (13.2 vs. 3.1%), comorbidity (age-adjusted Charlson Comorbidity Index [ACCI] ≥ 4; 36.8 vs. 13.3%), median body mass index (BMI; 27 vs. 24 kg/m2), International Federation of Gynecology and Obstetrics (FIGO) stage, histology (high-grade serous 95.6 vs. 84.7%), and complete resection (38.2 vs. 68.2%). MA < 32 HU remained a significant prognostic factor for OS in multivariate Cox regression analysis (hazard ratio 1.79, p = 0.003). Median OS in patients with MA < 32 HU versus MA ≥ 32 HU was 28 versus 56 months (p < 0.001). Furthermore, MA < 32 HU was significantly associated with OS in the prognostically poor population of patients with residual tumor (p = 0.015). CONCLUSIONS: Low MA was significantly associated with poor survival, especially in patients with residual tumor after PDS. MA assessment could be used for risk stratification after PDS.

Stage- and Histologic Subtype-Dependent Frequency of Lymph Node Metastases in Patients with Epithelial Ovarian Cancer Undergoing Systematic Pelvic and Paraaortic Lymphadenectomy.

PURPOSE: Tumor stage and distinct histological subtypes in epithelial ovarian cancer (EOC) show different prognostic outcome. The aim of this study is to evaluate whether the frequency of lymph node (LN) metastases in patients with different tumor stages and histological subtypes undergoing systematic pelvic and paraaortic lymphadenectomy is coincidentally divergent. METHODS: Patients with EOC treated with upfront staging or debulking surgery between January 2000 and December 2016 were included. Systematic lymphadenectomy was performed in all consecutive patients with optimal debulking and without medical contraindications. RESULTS: Seven hundred sixty-two patients including 27.2% with early-stage EOC were included. The median number of removed LNs was 69, and metastases to LNs were found in 54.7%. No LN metastases were found in patients with low-grade endometrioid carcinoma, independently of tumor stage. LN metastases in early-stage low-grade serous (N = 5), mucinous (N = 31), and clear cell (N = 28) EOC were found in one (20%), zero, and one (3.6%) patient, respectively. LN metastases were detected in more than 10% of patients with all other histological subtypes. On multivariate analyses, overall survival was significantly impaired in patients with LN metastases, as compared with patients without LN metastases (p = 0.001). CONCLUSIONS: The risk of LN metastases in patients with EOC is dependent on stage and histological subtype. Patients with incidental finding of early mucinous or low-grade endometrioid EOC are at very low risk of retroperitoneal lymph node metastases. Reoperation for lymph node staging only should be discussed individually with caution.

Prognostic Value of the Age-Adjusted Charlson Comorbidity Index (ACCI) on Short- and Long-Term Outcome in Patients with Advanced Primary Epithelial Ovarian Cancer.

BACKGROUND: We evaluated the prognostic impact of the age-adjusted Charlson Comorbidity Index (ACCI) on both postoperative morbidity and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) treated at a tertiary gynecologic cancer center. PATIENTS AND METHODS: Exploratory analysis of our prospectively documented tumor registry was performed. Data of all consecutive patients with stage IIIB-IV ovarian cancer who underwent primary cytoreductive surgery (PDS) from January 2000 to June 2016 were analyzed. Patients were divided into three groups, based on their ACCI: low (0-1), intermediate (2-3), and high (≥4), and postoperative surgical complications were graded according to the Clavien-Dindo classification (CDC). The Fisher's exact test, log-rank test, and Cox regression models were used to investigate the predictive value of the ACCI on postoperative complications and OS. RESULTS: Overall, 793 consecutive patients were identified; 328 (41.4%) patients were categorized as low ACCI, 342 (43.1%) as intermediate ACCI, and 123 (15.5%) as high ACCI. A high ACCI was significantly associated with severe postoperative complications (CDC 3-5; odds ratio 3.27, 95% confidence interval 1.97-5.43, p < 0.001). Median OS for patients with a low, intermediate, or high ACCI was 50, 40, and 23 months, respectively (p < 0.001), and the ACCI remained a significant prognostic factor for OS in multivariate analysis (p = 0.001). The same impact was observed in a sensitivity analysis including only those patients with complete tumor resection. CONCLUSION: The ACCI is associated with perioperative morbidity in patients undergoing PDS for EOC, and also has a prognostic impact on OS. The potential role of the ACCI as a selection criteria for different therapy strategies is currently under investigation in the ongoing, prospective, multicenter AGO-OVAR 19 trial.

The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery.

OBJECTIVE: To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. METHODS: We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. RESULTS: AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). CONCLUSION: In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections.