Early-stage Ovarian Carcinoma Research Articles

Perioperative management of a patient with unexpectedly detected early-stage ovarian mucinous carcinoma combined with progressive bulbar paralysis: a case report and literature review

BackgroundGiant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases.Case presentationIn this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml.ConclusionsGOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.

Abstract 7312: Construction of a gene panel for liquid biopsy-based diagnostics of gynecologic cancer

Abstract Background: Ovarian carcinoma (OC) is the leading cause of death from gynecologic cancers mainly due to late detection, where most patients are diagnosed at advanced stages (51% in stage III; 29% in stage IV). Despite an overall more favorable prognosis, endometrial carcinoma (EC) is the most common gynecologic cancer, with an increasing incidence and where some subtypes are associated with a poor prognosis. Identification of DNA mutations from precancerous lesions or early-stage OC and EC would allow for early intervention. Liquid biopsies through routine sampling such as endocervical sampling, or blood collection for isolation and analysis of ctDNA have previously been assessed for their use in detection of OC and EC. These studies have provided evidence that tumor-derived mutations can be detected in endocervical samples, supporting endocervical liquid biopsies as a potential source of ctDNA. Herein, we aimed to construct a diagnostic gene panel corresponding to common mutation profiles of OC and EC to detect early-stage malignancy through a non-invasive approach. Methods: Using the NGS-method, Simple multiplexed PCR-based barcoding of DNA for sensitive mutation detection using sequencing (SiMSen-Seq), a gene panel was constructed targeting hotspot mutations in known OC- and EC-associated genes. Hotspots were identified using the Catalogue of Somatic Mutations in Cancer (COSMIC) database or retrieved from the literature and assays were designed for amplification of short DNA fragments. Precise assay development was carried out including multiple steps of careful validation to ensure high specificity and efficient amplification. Individual assays were validated in multiple steps using qPCR and fragment analysis. Results: The gene panel was designed as two non-overlapping subunits for comprehensive diagnosis of OC and EC. The two constructed multiplexes, together composed of 125 single assays target genomic regions in 34 EC and OC-associated genes e.g., PTEN, TP53, PIK3CA and CTNNB1. Included assays had a median amplicon size of 92 bp (range 57-111 bp). Both multiplexes displayed good performance with distinguishable libraries at low DNA input (10 ng). Validation of individual assays showed high specificity and efficient amplification where >80% of assays displayed a sequencing coverage >500 UMI counts at a consensus depth of 3. Patient coverage calculations of COSMIC data suggested comparable coverage as similar published approaches. Conclusion: The results suggest that the constructed gene panel has great potential to detect mutations in liquid biopsies collected from the gynecologic tract, despite low tumor DNA levels. Validation of the two multiplexes by fragment analysis and sequencing showed high performance, hence, prospective for the approaching sequencing of liquid biopsies. Citation Format: Sara Schumacher, Therese Carlsson, Jacob Malchau Lauesgaard, Anna Linder, Amanda Olsson Widjaja, Karin Sundfeldt. Construction of a gene panel for liquid biopsy-based diagnostics of gynecologic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7312.

Premature Classification of Early-stage Endometrioid Ovarian Carcinoma With Mesonephric-like Differentiation as Mesonephric-like Adenocarcinoma.

Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.

Impact of the number of cycles of platinum-based chemotherapy for early stage ovarian clear cell carcinoma on survival: a retrospective study

BackgroundOvarian clear cell carcinoma (OCCC) is a unique subtype of ovarian epithelial ovarian cancer. The number of chemotherapy cycles for early-stage patients is still debated. This study aimed to evaluate whether at least 4 cycles of adjuvant platinum-based chemotherapy have better prognostic value than 1–3 cycles in early-stage OCCC.MethodsWe retrospectively retrieved data from 102 patients with stage I-IIA OCCC between 2008 and 2017. All patients underwent complete surgical staging followed by adjuvant platinum-based chemotherapy. Kaplan-Meier curves and Multivariate Cox analysis were performed to estimate 5-year overall survival (OS) and progression-free (PFS) according to the number of chemotherapy cycles.ResultsAmong stage I-IIA disease, twenty (19.6%) patients received 1–3 cycles, and eighty-two (80.4%) patients received at least 4 cycles of adjuvant chemotherapy. Univariate analysis revealed that the patients in 1-3cycles group had not significantly improved 5-year OS and PFS than those in the ≥ 4 cycles group (5-year OS: hazard ratio [HR] 1.21; 95% confidence interval [CI] 0.25– 5.78, p = 0.1), and 5-year PFS: HR 0.79; 95% CI 0.26– 2.34, p = 0.1). In the multivariate analysis, there was no impact of 1–3 versus ≥ 4 cycles of chemotherapy on 5-year OS (HR 1.21, 95% CI 0.25–3.89, p = 0.8) or 5-year PFS (HR 0.94, 95% CI 0.32–2.71, p = 0.9). The potential independent risk factors associated with 5-year OS and PFS included the surgery approach and FIGO stage.ConclusionThe number of cycles of platinum-based chemotherapy could not be associated with a survival benefit for patients with early-stage OCCC.

Abstract 3058: Colocalization of cancer-associated biomarkers on single extracellular vesicles for early-cancer detection

Abstract Introduction: Extracellular vesicles (EVs) are abundant in biological fluids and increasingly recognized for their diagnostic and therapeutic potential. Unlike circulating tumor DNA which scales in abundance with tumor size and is a product of tumor cell death; tumor EVs are secreted continuously, are remarkably stable, and used by cancer cells as messengers to benefit tumor growth and metastasis, suggesting they may be a better indicator of early-stage cancer. Tumor-derived EVs reflect their cell of origin, making them an ideal analyte for liquid biopsy diagnostic assays. We describe a platform technology, Mercy Halo™, which interrogates millions of individual EVs within a plasma or serum sample to capture and detect cancer cell derived EVs. Using panels of antibodies targeting up to three cancer-associated biomarkers simultaneously, we demonstrate Mercy Halo enables sensitive and specific detection of early-stage high-grade serous ovarian carcinoma (HGSOC) with excellent reproducibility in a proof-of-concept (PoC) study. Methods: Following purification of a sample by size-exclusion chromatography, EVs were captured using antibody-functionalized beads and interrogated using proximity ligation qPCR. EVs were characterized and biomarker expression confirmed by traditional immunoassay and Mercy Halo. The colocalization of specific biomarkers on single EVs was measured using a panel of antibodies against biomarkers upregulated in HGSOC and human cancer cell lines. Optimized antibody panels were then used in a feasibility study using EVs purified from plasma samples from early- and late-stage HGSOC, benign ovarian masses, and healthy controls. Results: Mercy Halo detects colocalized biomarkers specifically and sensitively on the surface of tumor derived EVs. Surface biomarkers expressed by cancer cells were detected in our assay and signal strength correlated with protein expression, demonstrating that EVs can be used as a surrogate to indicate the presence or absence of cancer. We demonstrate that biomarkers present on cancer cells are colocalized on EVs derived from a tumor and are readily detectable using the Mercy Halo platform. A positive signal was dependent on the presence of all biomarkers on the same EV. Importantly, there was significant improvement in both the specificity and sensitivity of the assay as the number of biomarker antibodies used to interrogate the EVs increases. Finally, in a small clinical cohort PoC study, we demonstrate improved detection of early stage HGSOC relative to CA125 ELISA. Conclusions: Tumor-derived EVs are a robust analyte for liquid-biopsy assays which can readily be detected using our platform technology. This PoC study suggests Mercy Halo can discriminate all stages of HGSOC from benign and healthy samples in human plasma with high sensitivity and specificity and is being investigated for extensibility in other cancers and diseases. Citation Format: Daniel P. Salem, Laura T. Bortolin, Anthony D. Couvillon, Dan Gusenleitner, Jonian Grosha, Sanchari Banerjee, Kelly M. Biette, Ibukunoluwapo O. Zabroski, Christopher R. Sedlak, Delaney M. Byrne, Peter A. Duff, Bilal F. Hamzeh, MacKenzie S. King, Lauren T. Cuoco, Emily S. Winn-Deen, Eric K. Huang, Joseph C. Sedlak. Colocalization of cancer-associated biomarkers on single extracellular vesicles for early-cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3058.

Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma.

Ovarian cancer (OC) is the leading cause of gynecological cancer-related death. Of the main OC histologic subtypes, invasive mucinous carcinomas (MC) account for only 3% of OC cases and are frequently associated with favorable prognosis. Nevertheless, MCs differ greatly from the other OC histotypes in clinical, pathological, and biological behavior. However, the origin and molecular pathogenesis of MC are not yet fully understood. Therefore, identification of novel diagnostic markers could potentially facilitate early diagnosis of OC, particularly the MC histotype, thereby leading to the development of histotype-specific treatment regimens and improved survival rates. In the present study, Trefoil factor gene family members (TFF1, TFF2 and TFF3) were identified as MC histotype-specific biomarkers using RNA sequencing (RNA-seq) data for 95 stage I-II OCs. The diagnostic value of TFF1, TFF2 and TFF3 was then evaluated by immunohistochemistry on 206 stage I-II OCs stratified by histotype (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], clear cell carcinoma [CCC], and MC). We showed significantly elevated intracytoplasmic protein expression levels for TFF1, TFF2 and TFF3 in MC samples, thereby revealing an association between expression of Trefoil factor gene family members and the MC histotype. Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype. Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype. Moreover, these novel histotype-specific diagnostic biomarkers may not only improve patient stratification of early-stage ovarian carcinomas but may also be candidates for the development of molecular targeted therapies.

Survival Outcomes in the Patients of Ovarian Epithelial Carcinomas Treated with Fertility-Sparing Surgery: A Study from a Developing Country

Objective: To assess the outcomes of fertility-sparing surgery in patients with ovarian epithelial carcinoma treated at our centre.
 Study Design: Retrospective longitudinal study.
 Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore Pakistan, from Jul 2001 to Aug 2015.
 Methodology: We studied 31 patients with ovarian epithelial carcinoma who underwent fertility-sparing surgery at Shaukat Khanum Memorial Hospital. The detail regarding patients and tumour characteristics, along with outcomes of the intervention, was obtained from secondary data kept in the electronic hospital information system.
 Results: A total of 132 patients with ovarian epithelial carcinoma were identified; 31 patients underwent fertility-sparing surgery (Stage-IA, n=19; Stage-IC, n=12). By histopathology, 14(45.0%) had mucinous cystadenocarcinoma, 7(22.6%) serous adenocarcinoma, 6(19.4%) endometroid, and 4(12.9%) with clear cell pathology. The mean duration of follow-up was 52.6±2.3 months (18-118 months) after fertility-sparing surgery. Five-year recurrence-free survival was 81.0%. (Three-year=89.0%), using the Kaplan-Meier graph. Three patients had successful pregnancies, with one having a twin pregnancy.
 Conclusion: Fertility-sparing surgery should be considered for children of early-stage epithelial ovarian carcinoma patients as it preserves fertility and endocrine function while avoiding recurrence.

Guideline adherence in ovarian cancer for surgical staging in the Netherlands

ObjectivePrevious studies have shown low adherence to surgical staging guidelines in patients with clinical early-stage ovarian carcinoma. The aim of this study was to identify guideline adherence for surgical staging...

Surgical staging of apparent early-stage ovarian mucinous carcinoma

ObjectivesThe aim of the study was to explore the rate of upstaging after complete surgical staging among patients with apparent FIGO stage I ovarian mucinous carcinoma.MethodsOvarian mucinous carcinoma patients with surgical treatment at the Peking Union Medical College Hospital between October 2020 and January 1994 were retrospectively reviewed.ResultsIn total, 163 patients were included in this study. Surgical restaging was performed in 89 patients after initial incomplete surgical staging, and one-step complete surgical staging was performed in 74 patients. Among these initially incompletely staged patients, residual tumors were found in 16 patients (16/89, 17.9%). Among the 19 patients with apparent FIGO stage IA, no patient was found to have residual tumors after incomplete staging surgery, according to the final pathology result of restaging surgery. Ovarian cystectomy (OR=4.932, 95% CI= 1.347–18.058, P=0.016) was an independent risk factor for residual tumors after incomplete staging surgery. Among all 163 patients, upstaging occurred in 15 patients (15/163, 9.2%). Among 44 apparent FIGO stage IA patients, no patient was upstaged to FIGO II–IVB. Moreover, both a history of ovarian mucinous tumor (OR=4.745, 95% CI= 1.132–19.886, P=0.033) and bilateral ovary involvement (OR=9.739, 95% CI= 2.016–47.056, P=0.005) were independent risk factors for upstaging to FIGO stage II–IVB.ConclusionsFor patients with apparent FIGO stage IA disease, the possibility of residual tumors and upstaging is relatively low. For patients with cystectomy, bilateral mucinous carcinomas, or a history of ovarian mucinous tumors, complete staging surgery maintains greater significance.

Impact of lymph node staging in presumed early-stage ovarian carcinoma

ObjectiveOur objective was to analyze the prevalence of lymph node metastasis in early-stage ovarian carcinoma after systematic lymph node dissection and its impact on indication of adjuvant chemotherapy. Study designWe evaluated a series of 765 patients diagnosed with ovarian carcinoma who underwent surgical treatment from February 2007 to December 2019. Patients with peritoneal disease and incomplete surgical staging were excluded. All cases underwent systematic pelvic and para-aortic lymphadenectomy up to the renal vessels. ResultsA total of 142 cases were analyzed. Median pelvic and para-aortic lymph node dissected were 30 (range, 6–81) and 21 (range, 3–86), respectively. Twelve (8.4%) patients had metastatic lymph nodes – high-grade serous, 10.4% (5/48); clear cell, 17.2% (5/29) and endometrioid, 5.7% (2/35). Any other histology (low grade serous, mucinous, carcinosarcoma or mixed) had lymph node metastasis. Notably, 50% of patients with positive lymph nodes had preoperative suspicious lymph nodes in imaging. The median hospital stay length was 6 days (range, 2–33) and 4.2% cases had grade ≥ 3 complications. A total of 110 (77.6%) patients underwent adjuvant chemotherapy and all cases had indication of adjuvant chemotherapy after histological type, despite the lymph node status. After a median follow-up of 52.5 months, we noted 24 (16.9%) recurrences. The 5-year recurrence-free survival and overall survival were 86.4% and 98.1%, respectively. High grade histology was the only variable that negatively impacted disease-free survival in univariate analysis [HR 4.70 (95%CI: 1.09–20); p = 0.037]. ConclusionsWe found a positive lymph node rate of less than 10% after lymphadenectomy in presumed early-stage ovarian carcinoma. Lymph node status was not determinant for adjuvant chemotherapy.

Robot-assisted laparoscopic staging compared to conventional laparoscopic staging and laparotomic staging in clinical early stage ovarian carcinoma.

Robot-assisted laparoscopic staging (RALS) is increasingly used for staging epithelial ovarian cancer (EOC). Evidence of its safety is limited. The aim of this review is to compare the efficacy and safety of RALS in clinical early-stage EOC to conventional laparoscopy and laparotomy and to assess the level of evidence that is currently available to adopt this surgical technique. Only retrospective studies comparing staging by minimally invasive surgery (MIS) to laparotomy are available. Both RALS and conventional laparoscopic staging shorten length of hospital stay (LHS, mean -2.9 days) and decrease estimated blood loss (EBL, mean -79 ml less) compared to laparotomy. Complication rates and number of lymph nodes collected are similar in all surgical staging techniques. Survival outcomes after staging by MIS cannot be compared to staging by laparotomy because of the lack of evidence but RALS is probably noninferior to conventional laparoscopic staging. RALS probably improves perioperative outcomes in patients with clinical early stage EOC similar to conventional laparoscopic staging. Whether oncologic outcomes of RALS are comparable to open and conventional approaches is uncertain as there is only level C evidence and randomized controlled trials are urgently needed to confirm the current retrospective findings.

Role of lymphadenectomy for apparent early-stage low-grade serous ovarian carcinoma (529)

<b>Objectives:</b> To investigate the incidence of lymph node (LN) metastasis and the impact of lymphadenectomy (LND) on the survival of patients with apparent early-stage low-grade serous ovarian carcinoma (LGSOC). <b>Methods:</b> Patients with apparent FIGO stage I (or T1/Nx/M0) LGSOC diagnosed between 2004 and 2015 who underwent surgery were drawn from the National Cancer Database. Performance of LND and incidence of LN metastasis were assessed from pathology report. Overall survival (OS) was evaluated following generation of Kaplan- Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected confounders. In a sensitivity analysis, impact of LND on the survival of patients with FIGO stage I disease was evaluated. <b>Results:</b> A total of 977 patients with LGSOC were identified; 592 (60.6%) patients with apparent stage IA/IB, and 385 (39.4%) patients with apparent stage IC disease. The overall rate of LND was 65.9%: 69.4%, and 63.7% for apparent stage IA/IB and IC disease, respectively (p=0.068). The median number of LN removed was 12 (interquartile range: 14). Patients who did and did not undergo LND were comparable in terms of patient age, race, insurance status, and type of treatment facility. However, the rate of chemotherapy use was higher in the LND group compared to the group that did not undergo LND (33.5% vs 26.4%, p=0.024). The overall incidence of LN metastasis was 7.5%: 5.6% for stage IA and 10.1% for stage IC (p=0.031). The rate of LN metastasis was higher for patients who had comprehensive LND (defined as ≥10 LNs removed) compared to those who had limited LND (defined as 1-9 LNs removed; 9% vs 4.8% respectively, p=0.048). The Median follow-up of the cohort was 70.34 months. Patients who underwent LND had better OS compared to those who had did not (p<0.001); 5-yr OS were 91.6% and 83.3%, respectively. After controlling for patient age, race, presence of medical comorbid conditions, and intra-abdominal tumor extent (IA/IB vs IC), the performance of LND was associated with better OS (HR: 0.63, 95% CI: 0.45, 0.87). In a sensitivity analysis, a total of 754 patients with FIGO stage I disease were included, and after controlling for confounders, the performance of LND was associated with better OS (HR: 0.66, 95% CI: 0.44, 0.98). <b>Conclusions:</b> Lymphadenectomy will detect lymph node metastases in up to 10% of patients with apparent stage I LGSOC, while it is associated with a survival benefit likely secondary to stage migration. Comprehensively staging in apparent early-stage patients with LGSOC appears to be warranted since the identification of patients with occult stage III disease can alter adjuvant treatment recommendations.

Oncological and Reproductive Outcomes After Fertility-Sparing Surgery for Stage I Mucinous Ovarian Carcinoma.

BackgroundFertility-sparing surgery (FSS) has been widely used for patients with early-stage mucinous ovarian carcinoma (MOC). However, there is limited evidence regarding the reproductive outcomes as well as the impact of growth pattern on oncological outcomes after FSS. This study aims to evaluate the oncological and reproductive outcomes of patients with stage I primary MOC after FSS.MethodsThis retrospective study enrolled 159 women with histologically confirmed unilateral stage I MOC treated at Peking Union Medical College Hospital between 1997 and 2019. Sixty-seven cases were pathologically reviewed for the growth pattern. Seventy-eight patients had FSS, defined as conservation of the uterus and at least part of one ovary, while 81 underwent radical surgery (RS). Oncofertility outcomes were compared between the groups and clinicopathological factors associated with disease-free survival (DFS) were analyzed by univariate and multivariate analyses. Patients in the FSS group were contacted to collect data on reproductive outcomes.ResultsEighteen patients developed recurrent disease during a median follow-up of 69 months, including 12 in the FSS and six in the RS group. There was one death each in the FSS and RS groups. There was no significant difference in DFS between the groups. CA125 >35 U/ml, stage IC, and incomplete staging were correlated with worse DFS according to multivariate analysis (P=0.001; 0.020 (stage IC) and 0.004 (incomplete staging) respectively). There was no significant difference in DFS between patients with stage IA and stage IC1 in the FSS group, while DFS was poorer in patients with stage IC2/3 than stage IA (P=0.028). In addition, DFS was significantly poorer in patients who underwent unilateral salpingo-oophorectomy (USO) compared with those receiving USO plus staging surgery (P=0.015). There was a tendency towards poorer DFS in the infiltrative tumors compared with the expansile tumors (P=0.056). Of 23 patients who attempted to conceive, 21 (91.3%) achieved 27 pregnancies, including 26 spontaneous pregnancies and one following assisted reproductive technology. Twenty patients gave birth to 24 healthy babies, including 21 full-term and three premature births. The live-birth rate was 88.9%.ConclusionsFSS is a suitable option for young women with unilateral stage I expansile MOC, with acceptable oncological outcomes and meaningful pregnancy rates. Re-staging should be proposed in patients who undergo incomplete staging surgery.

Abstract 53: The copy number landscape of early stage ovarian high grade serous carcinoma

Abstract Background: High grade serous carcinoma (HGSC) is the most common and poorest prognosis subtype of ovarian cancer. The large majority of patients present with advanced (stage IIIC or IV) disease with a median survival of only 3-4 years. By contrast, approximately 10% patients are diagnosed with early stage disease, confined to the ovary/fallopian tube, of whom 90% are cured with surgery and platinum-based chemotherapy. Beyond TP53 mutation, classic activating oncogene mutations are rare in HGSC. Rather, HGSC is marked by extreme copy number (CN) abnormalities, and this complexity has prevented detailed understanding of the mutational processes underpinning outcomes in HGSC. We have used shallow whole genome sequencing (sWGS) to develop novel CN signatures that are able to deconvolute the complexity of HGSC genomes. However, nearly all genomics studies in HGSC have examined advanced stage disease, and little is known about the genomics of early stage HGSC - specifically, it is unclear whether these tumors are identified purely by chance or whether they represent a specific subset that does not metastasize. Hypotheses: We hypothesized that early stage HGSC has a distinct copy number landscape compared to stage IIIC/IV disease. Methods and results: We have identified 43 cases of FIGO stage I-IIA HGSC from the pathology archives of three large London Gynaecological Cancer Centres and 52 late-stage (stage IIIC-IV) cases from BriTROC-1 cohort. Median age at diagnosis was 61.3 years vs 62.3 years respectively. There were no significant differences in mutation rates of TP53 and BRCA1/2, and TP53 mutations were near-universal in both cohorts. We also did not find cohort-specific focal SCNA that could explain biological behavior. However, ploidy was significant higher in late-stage (median 3.0) than early-stage (median 1.9) samples. CN signature exposures were significantly different between early and late stage cohorts. Relative exposure of signature 3 was greater in early-stage and greater signature 4 in late-stage. Unsupervised clustering based on CN signatures identified three clusters that were prognostic. Summary:This project identifed that early stage and late stage HGSC have highly similar patterns of mutation and focal SCNA. However, genome-wide analysis indicates that the abnormalities seen in advanced disease are not present in early stage disease, which may represent a discrete subset with reduced metastatic potential. By identifying and characterizing the copy number signature changes, these data suggest that diagnosis at early-stage might reflect biological differences and not fortuitous chance. These data improve understanding of HGSC biology and may reveal potential new treatment strategies. Citation Format: Zhao Cheng, Hasan B. Mirza, Darren P. Ennis, Philip Smith, Lena Morrill Gavarró, Chishimba Sokota, Gaia Giannone, Teodora Goranova, Thomas Bradley, Anna Piskorz, Michelle Lockley, Baljeet Kaur, Naveena Singh, Laura A. Tookman, Jonathan Krell, Jackie McDermott, Geoff Macintyre, Florian Markowetz, James D. Brenton, Iain A. McNeish. The copy number landscape of early stage ovarian high grade serous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 53.

Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis

ObjectiveIn young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients’ survival.MethodsBetween 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts.ResultsDuring 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234–1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330–2.669), P = 0.905}.ConclusionsEven after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

Gynecological malignancies

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)

Exploration of Potential Diagnostic Value of Protein Content in Serum Small Extracellular Vesicles for Early-Stage Epithelial Ovarian Carcinoma.

Epithelial ovarian carcinoma (EOC) is one of the most common gynecologic malignancies with a high mortality rate. Serum biomarkers and imaging approaches are insufficient in identifying EOC patients at an early stage. This study is to set up a combination of proteins from serum small extracellular vesicles (sEVs) for the diagnosis of early-stage EOC and to determine its performance. A biomarker for early-stage ovarian cancer (BESOC) cohort was used as a Chinese multi-center population-based biomarker study and registered as a Chinese Clinical Trial ChiCTR2000040136. The sEV protein levels of CA125, HE4, and C5a were measured in 299 subjects. Logistic regression was exploited to calculate the odds ratio and to create the sEV protein model for the predicted probability and subsequently receiver-operating characteristic (ROC) analysis. The combined sEV marker panel of CA125, HE4, and C5a as a sEV model obtained an area under curve (AUC) of 0.912, which was greater than the serum model (0.809), by ROC analysis to identify EOC patients from the whole cohort. With the cutoff of 0.370, the sensitivity and specificity of the sEV model were 0.80 and 0.89, which were much better performance than the serum markers (sensitivity: 0.55~0.66; specificity: 0.59~0.68) and the risk of ovarian malignancy algorithm (ROMA) index approved by the U.S. Food and Drug Administration (sensitivity: 0.65; specificity: 0.61), to identify EOC patients from patients with benign ovarian diseases or other controls. The sEV levels of CA125 significantly differed among early-stage and late-stage EOC (p < 0.001). Moreover, the AUC of ROC to identify early-stage EOC patients was 0.888. Further investigation revealed that the sEV levels of these 3 proteins significantly decreased after cytoreductive surgery (CA125, p = 0.008; HE4, p = 0.025; C5a, p = 0.044). In summary, our study showed that CA125, HE4, and C5a levels in serum sEVs can identify EOC patients at the early stage, elucidating the possibility of using a sEV model for the diagnosis of early-stage EOC.

Lymphadenectomy for early-stage mucinous ovarian carcinoma

ObjectivesThere is evidence to suggest that the rate of lymph node metastases in patients with ovarian mucinous tumors is rare. The objective of this study was to investigate the prevalence...

Is there any utility in performing lymphadenectomy for early-stage mucinous ovarian carcinoma?

Objective: The aim of this study was to investigate the prevalence of regional lymph node metastasis among patients with clinical stage I and II mucinous ovarian carcinoma (MOC).

Use of adjuvant chemotherapy for early-stage low-grade serous ovarian carcinoma

Objective: The aim of this study was to investigate patterns of use and the impact of adjuvant chemotherapy on overall survival (OS) of patients with stage IC and II low-grade serous ovarian carcinoma (LGSOC).