Mucinous ovarian carcinoma: A survey of practice in Australia and New Zealand.

BACKGROUND: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer with limited evidence to support clinical care. AIMS: We undertook a clinician survey to better understand current practice in treating MOC in Australia and New Zealand, and to determine any features associated with variation in care. In addition, we aimed to understand future research priorities. METHODS: A RedCap survey was distributed to clinician members of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). Questions included respondent demographics, three case studies and future research priorities. Clinicians were asked questions specific to their speciality. RESULTS: Respondents (n = 47) were commonly experienced gynae-oncology specialists, most often surgical (38%) or medical (30%) oncologists. There was good consensus for surgical approaches for stage I disease; however, variation in practice was noted for advanced or recurrent MOC. Variation was also observed for medical oncologists; in early-stage disease there was no clear consensus on whether to offer chemotherapy, or which regimen to recommend. For advanced and recurrent disease a wide range of chemotherapy options was considered, with a trend away from an ovarian-type toward gastrointestinal (GI)-type regimens in advanced MOC. This practice was reflected in future research priorities, with 'Is a GI chemotherapy regimen better than an ovarian regimen?' the most highly ranked option, followed by 'Should stage 1C patients receive chemotherapy?' CONCLUSIONS: Although the number of respondents limited the analyses, it was clear that chemotherapy selection was a key point of divergence for medical oncologists. Future research is needed to establish well-evidenced guidelines for clinical care of MOC.

Safety of fertility sparing management in invasive mucinous ovarian carcinoma.

BACKGROUND: The aim of the study was to evaluate the safety of fertility-sparing surgery in invasive mucinous ovarian carcinomas (MOC). METHODS: Retrospective review was performed of MOCs diagnosed between 1999 and 2019 at two tertiary cancer centers. Pathology was reviewed to rule out metastasis from gastrointestinal tract. The demographics and survival outcomes were compared between women who underwent fertility-sparing surgery and those who underwent radical surgery (at least hysterectomy, bilateral salpingo-oophorectomy +/- staging). Cox proportional hazard models were constructed to evaluate the effect of fertility sparing surgery on survival. RESULTS: Of 134 with stage I disease, 42 (31%) underwent fertility-sparing surgery with unilateral salpingo-oophorectomy. Compared to women who underwent radical surgery, these women were younger with low grade, early-stage disease. Two patients (5%) in the fertility-sparing cohort experienced a recurrence and 1 of these 2 patients died due to disease progression. There was no difference in either OS or RFS between those that underwent fertility-sparing surgery and radical surgery. In a multivariable analysis adjusting for age and use of adjuvant chemotherapy, fertility-sparing surgery was not significantly associated with OS (HR 0.18; 95% CI 0.01-2.78) or RFS (HR 0.19; 95% CI 0.03-1.45). There were 4 patients (9%) with documented full-term delivery with median interval to conception of 11 months. CONCLUSIONS: Fertility-sparing surgery in stage I MOC is not associated with worse outcomes compared to radical surgery and is reasonable to offer to those with early stage disease who wish to retain fertility.

Clinical implications of histologic subtypes on survival outcomes in primary mucinous ovarian carcinoma.

OBJECTIVE: In 2014, the World Health Organization introduced a new histologic classification by dividing primary mucinous ovarian carcinoma (PMOC) into two: expansile (ES) or infiltrative subtypes (IS). This study investigated the clinical implications of these histological subtypes on survival outcomes. METHODS: Data from 131 patients with PMOC who underwent primary surgery between 2003 and 2021 were analyzed. The patients baseline characteristics, surgical and pathological information were collected. Survival outcomes were calculated, while factors affecting them were also investigated. RESULTS: During 55.9 months of median follow-up, 27 (20.6%) patients experienced recurrence and 20 (15.3%) died. Among 131 patients, 113 patients were classified into 87 (77%) ES and 26 (23%) IS after a slide review. Advanced stage, lymph node involvement, and residual tumors after surgery were more common in the IS, showing poorer prognosis. In multivariate analyses, advanced stage and residual tumors after surgery were associated with worse survival, while the IS showed no statistical significance. In subgroup analysis for stage I disease, survival did not vary between subtypes. Nevertheless, patients in the IS group who underwent fertility-sparing surgeries demonstrated a 5-year progression-free survival (PFS) rate of 83.3%, significantly lower than patients without fertility preservation, irrespective of histologic subtypes (5-year PFS rate: 97.9%; P = 0.002 for the ES, 5-year PFS rate: 100%; P = 0.001 for the IS). CONCLUSIONS: The IS of PMOC had poorer survival outcomes and a higher proportion of advanced-stage tumors. Although its independent prognostic significance remains uncertain, adjuvant chemotherapy should be considered for patients with fertility preservation in the IS group.

Synergy of the microRNA Ratio as a Promising Diagnosis Biomarker for Mucinous Borderline and Malignant Ovarian Tumors.

Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival of 11% for advanced stages (III/IV). At the early stages, these malignant forms are clinically difficult to distinguish from borderline (15%) and benign (80%) forms with a better prognosis due to the large size and heterogeneity of mucinous tumors. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in tumor progression and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, the comparison of miRNA microarray expression profiles between malignant and borderline tumor FFPE samples identified 10 down-regulated and 5 up-regulated malignant miRNAs, which were validated by individual RT-qPCR. To overcome normalization issues and to improve the accuracy of the results, a ratio analysis combining paired up-regulated and down-regulated miRNAs was performed. Although 21/50 miRNA expression ratios were significantly different between malignant and borderline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 pairs of miRNA ratios (double ratio) showed high discriminatory potential, with 100% of accuracy in distinguishing malignant and borderline ovarian tumors, which suggests that miRNAs may hold significant clinical potential as a diagnostic tool. In summary, these ratio miRNA-based signatures may help to improve the precision of histological diagnosis, likely to provide a preoperative diagnosis in order to adapt surgical procedures.

Long term survival outcomes of stage I mucinous ovarian cancer - A clinical calculator predictive of chemotherapy benefit.

OBJECTIVES: To determine the long-term potential benefit of adjuvant chemotherapy in subgroups of high-risk stage I mucinous ovarian cancer patients using a predictive scoring algorithm. METHODS: Data were collected from the National Cancer Database from 2004 to 2014. Based on demographic and surgical characteristics, a novel 10-year survival prognostic scoring system was developed using Cox regression. RESULTS: There were 2041 eligible patients with stage I mucinous ovarian cancer including 1362 (67%) with stage IA/IB disease, 598 (29%) with stage IC disease, and 81 (4%) with stage I disease not otherwise specified. Median age was 52 with a range of 13-90 years old. 737 (36%) patients were treated with adjuvant chemotherapy. Adjuvant chemotherapy was more common in patients with stage IC relative to stage IA/IB disease (69% vs. 21%, P < 0.001) or with poorly-differentiated relative to well-differentiated tumors (69% vs. 23%, P < 0.001). Unadjusted 10-year survival was 81% relative to 79% for patients treated with vs. without chemotherapy, respectively (P = 0.46). Patients were predicted to exhibit a low- or a high-risk of death using a multivariate Cox regression model with age, stage, grade, lymphovascular space invasion and ascites. Risk of death without vs. with adjuvant chemotherapy was similar in low-risk patients (88% vs. 84%; HR = 0.80, 95%CI = 0.56-1.15, P = 0.23) and worse in high-risk patients (51% vs. 74%; HR = 1.58, 95%CI: 1.05-2.38, P = 0.03) with stage I mucinous ovarian cancer. CONCLUSIONS: A predictive scoring algorithm may provide prognostic information on long-term survival and identify high-risk stage I mucinous ovarian cancer patients who might achieve a survival benefit from adjuvant chemotherapy.

Offspring sex and risk of epithelial ovarian cancer: a multinational pooled analysis of 12 case-control studies.

While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR = 1.45; 95% CI = 1.01-2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR = 1.71 vs 0.99; P-interaction = 0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR = 1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR = 0.49, 95% CI = 0.28-0.83) but with higher risk among women without any of those conditions (OR = 1.64 95% CI = 1.14-2.34; P-interaction = 0.003). Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC risk.

Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas.

BACKGROUND: Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers. METHODS: Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas (n = 206) using immunohistochemistry (IHC). RESULTS: We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients (P value = 0.026, HR = 2.99 (95% CI 1.089-8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival (P value = 0.00043, HR = 6.13 (95% CI 1.98-18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease-specific survival in clear-cell ovarian carcinoma patients (P value = 0.012, HR = 0.22 (95% CI 0.058-0.80); P value = 0.003, HR = 0.17 (95% CI 0.043-0.64)). CONCLUSIONS: The novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients.

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.

OBJECTIVES: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. METHODS: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms. CONCLUSION: mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.

Effectiveness of postoperative chemotherapy for stage IC mucinous ovarian cancer.

OBJECTIVE: To examine the association between postoperative chemotherapy and survival of women with stage IC mucinous ovarian cancer (MOC). METHODS: Comprehensive nationwide tumor registry data from the Commission on Cancer-accredited facilities in the United States from 2004 to 2014 were retrospectively examined. Women with stage IC MOC who underwent primary surgery followed by postoperative chemotherapy were compared to those who did not receive. Clinico-pathological factors associated with chemotherapy use, and overall survival associated with chemotherapy use were examined with multivariable models and propensity score inverse probability of treatment weighting (IPTW). External validation was performed by examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2014. RESULTS: There were 532 (58.5%) women who received postoperative chemotherapy and 377 (41.5%) women who did not. On multivariable analysis, those with moderately-/poorly-differentiated tumors, large tumor size, and who underwent lymphadenectomy were more likely to receive postoperative chemotherapy whereas young women and those with capsule rupture alone were less likely to receive postoperative chemotherapy (all, P < 0.05). After IPTW, there was no difference in overall survival among women who received postoperative chemotherapy versus those who did not on multivariable analysis (adjusted 4-year rates: 85.8% versus 86.3%, adjusted-hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.60-1.31). Similarly, there was no benefit with chemotherapy regardless of patient age, tumor differentiation, performance of nodal dissection, and substage groups. Among 912 cases in the validation cohort (postoperative chemotherapy use, n = 520 [57.0%]), postoperative chemotherapy use was not associated with cause-specific survival (adjusted-HR 1.296, 95% CI 0.846-1.984, P = 0.233) or overall survival (adjusted-HR 1.131, 95% CI 0.849-1.508, P = 0.400). CONCLUSION: Postoperative chemotherapy was received by fewer than 60% of women with stage IC MOC, and postoperative chemotherapy was not associated with improved survival.

Mucinous borderline ovarian tumor versus invasive well-differentiated mucinous ovarian cancer: Difference in characteristics and outcomes.

OBJECTIVE: Mucinous borderline ovarian tumor (mucinous-BOT) and invasive well-differentiated mucinous ovarian cancer (mucinous-OC) are often histopathologically misclassified. The objective of this study was to examine differences in clinico-pathological characteristics and outcomes of these two entities. METHODS: This is a retrospective population-based study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Stage I mucinous-BOTs and stage I well-differentiated mucinous-OC were compared for patient demographics, tumor characteristics, and outcomes. Propensity score matching and multivariable analysis were used to assess cause-specific survival (CSS). RESULTS: A total of 2130 mucinous-BOT and 581 mucinous-OC cases were examined for analysis. On multivariable analysis, women with mucinous-OC were more likely to be older, Eastern U.S. residents, and have undergone hysterectomy or lymphadenectomy compared to those with mucinous-BOT, and the number of women diagnosed with mucinous-OC decreased over time (all, P < 0.05). Mucinous-OCs were more likely to be stage T1c and have a smaller tumor size as compared to mucinous-BOT (both, adjusted-P < 0.05). After propensity score matching, women with mucinous-OC had significantly poorer CSS compared to those with mucinous-BOT on multivariable analysis (10-year rates: 92.7% versus 97.5%, adjusted-hazard ratio [HR] 2.03, P = 0.007). Similar results were observed among subgroups for reproductive age, stage T1a disease, large tumor, and unstaged cases (all, P < 0.05). CONCLUSION: Stage I mucinous-BOT and stage I invasive well-differentiated mucinous-OC have distinct differences in clinical characteristics and patient survival. The inability to conduct centralized pathology review in our study limits our conclusions given the recognized issue of misclassification of mucinous-BOT and mucinous-OC, but further highlights the importance of making the proper histopathological diagnosis for invasive cancer when the ovarian tumor is of mucinous histology.

A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen.

OBJECTIVE: We described progression-free survival and overall survival in patients with primary mucinous ovarian cancer receiving adjuvant gynecologic versus gastrointestinal chemotherapy regimens. METHODS: We identified all primary mucinous ovarian cancer patients receiving adjuvant gynecologic or gastrointestinal chemotherapy regimens at a single institution from 1994 to 2016. Gynecologic pathologists using strict pathologic/clinical criteria determined diagnosis. Adjuvant therapy was coded as gynecologic or gastrointestinal based on standard agents and schedules. Clinical/pathologic/treatment characteristics were recorded. Wilcoxon rank-sum test was used for continuous variables, and Fisher's exact test for categorical variables. Progression-free and overall survival were calculated using the Kaplan-Meier method, applying landmark analysis. RESULTS: Of 62 patients identified, 21 received adjuvant chemotherapy: 12 gynecologic, 9 gastrointestinal. Median age (in years) at diagnosis: 58 (range 25-68) gynecologic cohort, 38 (range 32-68) gastrointestinal cohort (p=0.13). Median body mass index at first post-operative visit: 25 kg/m2 (range 18-31) gynecologic cohort, 23 kg/m2 (range 18-31) gastrointestinal cohort (p=0.23). History of smoking: 6/12 (50%) gynecologic cohort, 3/9 (33%) gastrointestinal cohort (p=0.66). Stage distribution in gynecologic and gastrointestinal cohorts, respectively: stage I: 9/12 (75%) and 3/9 (33%); stage II: 2/12 (17%) and 1/9 (11%); stage III: 1/12 (8%) and 5/9 (56%) (p=0.06). Grade distribution in gynecologic and gastrointestinal cohorts, respectively: grade 1: 8/12 (67%) and 1/9 (13%); grade 2/3: 4/12 (33%) and 7/9 (88%) (p=0.03). Three-year progression-free survival: 90.9% (95% CI 50.8% to 98.7 %) gynecologic, 53.3% (95% CI 17.7% to 79.6%) gastrointestinal. Three-year overall survival: 90.9% (95% CI 50.8% to 98.7%) gynecologic, 76.2% (95% CI 33.2% to 93.5%) gastrointestinal. CONCLUSION: Ongoing international collaborative research may further define associations between chemotherapy regimens and survival.

Early stage mucinous ovarian cancer: A review.

Mucinous ovarian carcinomas (MOCs) are an uncommon subset of epithelial neoplasms, both clinically and molecularly distinct from other ovarian cancers. Pathologic diagnosis proves challenging, and metastatic disease from other sites-especially the digestive tract-must be excluded. Fortunately, most patients are diagnosed at an early stage of disease and often present with large, unilateral adnexal masses. Survival for patients with stage IA disease approaches over 90%, and surgery alone is sufficient. Patients with stage IB-II disease should receive adjuvant treatment but the specific regimen is controversial. In the following review, we provide an overview of mucinous ovarian carcinomas, with a particular focus on the treatment of patients with early stage disease.

Massively parallel sequencing analysis of mucinous ovarian carcinomas: genomic profiling and differential diagnoses.

OBJECTIVE: Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer resistant to standard chemotherapy regimens. We sought to characterize the repertoire of somatic mutations in MOCs and to define the contribution of massively parallel sequencing to the classification of tumors diagnosed as primary MOCs. METHODS: Following gynecologic pathology and chart review, DNA samples obtained from primary MOCs and matched normal tissues/blood were subjected to whole-exome (n = 9) or massively parallel sequencing targeting 341 cancer genes (n = 15). Immunohistochemical analysis of estrogen receptor, progesterone receptor, PTEN, ARID1A/BAF250a, and the DNA mismatch (MMR) proteins MSH6 and PMS2 was performed for all cases. Mutational frequencies of MOCs were compared to those of high-grade serous ovarian cancers (HGSOCs) and mucinous tumors from other sites. RESULTS: MOCs were heterogeneous at the genetic level, frequently harboring TP53 (75%) mutations, KRAS (71%) mutations and/or CDKN2A/B homozygous deletions/mutations (33%). Although established criteria for diagnosis were employed, four cases harbored mutational and immunohistochemical profiles similar to those of endometrioid carcinomas, and one case for colorectal or endometrioid carcinoma. Significant differences in the frequencies of KRAS, TP53, CDKN2A, FBXW7, PIK3CA and/or APC mutations between the confirmed primary MOCs (n = 19) and HGSOCs, mucinous gastric and/or mucinous colorectal carcinomas were found, whereas no differences in the 341 genes studied between MOCs and mucinous pancreatic carcinomas were identified. CONCLUSIONS: Our findings suggest that the assessment of mutations affecting TP53, KRAS, PIK3CA, ARID1A and POLE, and DNA MMR protein expression may be used to further aid the diagnosis and treatment decision-making of primary MOC.

Associations between residual disease and survival in epithelial ovarian cancer by histologic type.

OBJECTIVE: Surgical cytoreduction has been postulated to affect survival by increasing the efficacy of chemotherapy in ovarian cancer. We hypothesized that women with high-grade serous ovarian cancer, which usually responds to chemotherapy, would derive greater benefit from complete cytoreduction than those with histologic subtypes that are less responsive to chemotherapy, such as mucinous and clear cell carcinoma. METHODS: We conducted a retrospective cohort study of patients who underwent primary cytoreductive surgery and adjuvant chemotherapy for stage IIIC or IV epithelial ovarian cancer from 2011 to 2013 using data from the National Cancer Database. We constructed multivariable models to quantify the magnitude of associations between residual disease status (no residual disease, ≤1cm, or >1cm) and all-cause mortality by histologic type among women with clear cell, mucinous, and high-grade serous ovarian cancer. Because 26% of the sample had unknown residual disease status, we used multiple imputations in the primary analysis. RESULTS: We identified 6,013 women with stage IIIC and IV high-grade serous, 307 with clear cell, and 140 with mucinous histology. The association between residual disease status and mortality hazard did not differ significantly among histologic subtypes of ovarian cancer (p for interaction=0.32). In covariate adjusted models, compared to suboptimal cytoreduction, cytoreduction to no gross disease was associated with a hazard reduction of 42% in high-grade serous carcinoma (hazard ratio [HR]=0.58, 95% confidence interval [CI]=0.49-0.68), 61% in clear cell carcinoma (HR=0.39, 95% CI=0.22-0.69), and 54% in mucinous carcinoma (HR=0.46, 95% CI=0.22-0.99). CONCLUSIONS: We found no evidence that surgical cytoreduction was of greater prognostic importance in high-grade serous carcinomas than in histologies that are less responsive to chemotherapy.

Mucinous epithelial ovarian carcinoma.

Mucinous tumours involving the ovary may be benign, borderline, or malignant. Malignant tumours may be primary or metastatic. Differentiation between primary and metastatic involvement of the ovary is critical for optimal patient management. Even among skilled pathologists, this distinction can be problematic, as can the distinction between borderline ovarian tumour of intestinal type and well-differentiated invasive primary mucinous ovarian carcinoma. Primary invasive mucinous ovarian carcinoma and mucinous carcinoma metastatic to the ovary do have distinct patterns of macroscopic and microscopic involvement which will reveal the correct diagnosis in many cases. There are also well-recognized patterns of immunohistochemical staining that can further assist in this differentiation. As a result of the application of these histopathological techniques, the incidence of primary invasive mucinous epithelial carcinoma has fallen over recent years from ∼12% to ∼3%. However, even in recent multicentre clinical trials such as GOG 182, expert pathological review suggests that ∼60% of tumours originally classified as primary invasive mucinous carcinomas were in fact metastatic tumours to the ovary. Review of outcome data for patients with mucinous carcinoma entered into multicentre trials suggests that this subtype of disease has a particularly poor prognosis in comparison with other subtypes of ovarian carcinoma. Historically, patients with mucinous epithelial ovarian carcinoma (mEOC) have been treated in the same way as other subtypes of ovarian carcinoma. While there is undoubtedly a response rate to platinum-based chemotherapy, retrospective reviews of individual centre experience suggest that this is substantially lower than for high-grade papillary serous carcinoma and in the order of only 30%-40%. The mEOC trial was established to investigate the possibility that the combination of capecitabine and oxaliplatin (chemotherapy drugs more commonly used in colorectal carcinoma) may be superior to conventional carboplatin and paclitaxel chemotherapy. In a 2 × 2 factorial design, there was also a randomization to bevacizumab. Unfortunately, this trial closed early, 5 years after initiation having recruited just 50 of a proposed 322 patients. mEOC is now characterized as a type I tumour with an identifiable stepwise progression from a premalignant lesion, through non-invasive, to invasive malignancy. Molecular characterization of mEOC reveals it to be distinct from other subtypes of the disease with a KRAS mutation occurring in 40%-50% of patients. Other gene abnormalities including HER2 amplification in ∼19% also occur. This raises the possibility of the use of targeted molecular therapies which with molecular analysis of individual patient tumours could form the basis of a future clinical trial. It is, however, clear that if trials are to be conducted in this rare subtype of disease, they will need to be truly international in nature and carefully designed, possibly using an adaptive stepwise approach and will require an appropriate level of funding with a realistic assessment of likely recruitment. Associated translational research will clearly be essential.

Is routine gastrointestinal endoscopy required in every woman with mucinous ovarian cancer? An analysis of survival rates and metastatic tumours in a cancer centre.

INTRODUCTION: Mucinous ovarian cancer (MOC) represents a rare entity of ovarian malignant neoplasms. The true incidence could be as low as 3% of all ovarian cancers. The aim of this study is to compare and understand the clinicopathological characteristics of patients with mucinous ovarian cancer, report on the survival rates and evaluate the role of gastrointestinal (GI) endoscopy as part of the peri-operative investigations and the impact it has on the survival rates. METHODOLOGY: This is a retrospective data collection on patients with MOC operated in Nottingham gynaecological oncology centre over a 10-year period. Data were analysed using SPSS software. RESULTS: 43 cases were included in the final analysis. The median maximal tumour diameter was 180 mm. 32 (74.5 %) and 11 (25.5 %) women presented with unilateral and bilateral tumours respectively. 30 patients (69.7 %) presented with stage 1 disease, 1 (2.3 %) presented with stage 2 disease, 7 women (16.4 %) had stage 3 disease and 1 woman (11.6 %) had stage 4 disease. 41 women had staging surgical procedures and 2 women had limited surgery due to poor performance status. After final histology, 5 cases found to have metastatic disease to the ovary rather than primary MOC. 14 women had GI endoscopy as part of their investigation. The total estimated cost of the endoscopies that have been performed is £5635. Primary GI cancer was diagnosed in 1 case during the endoscopy (1 case of gastric cancer). The 5-year overall survival of the women included in this study is 62.8 %. The 5-year overall survival of the women in the endoscopy and non-endoscopy groups was 60 % and 64.3 % respectively (p-value: 0.767). CONCLUSION: The findings of this study show that the survival rates of patients treated for mucinous ovarian cancer in our centre are similar to other published studies. Our findings do not support the routine use of GI endoscopy in the peri-operative investigations of every patient with MOC due to the non-statistically significant difference in the overall survival.

Entrectinib use in a platinum-refractory mucinous ovarian cancer harboring a NTRK3 gene fusion.

Ovarian cancer is difficult to treat, and the mucinous epithelial subtype has a particularly poor response to traditional chemotherapy regimens. Entrectinib is a tumor-agnostic tyrosine kinase inhibitor with limited data regarding its use in ovarian cancers, though it demonstrates significant tumor response and patient tolerability in other settings. Here we outline what we believe to be the first case in which Entrectinib was successfully utilized to treat a patient with mucinous ovarian cancer. A 51-year-old woman with stage IVB mucinous ovarian cancer possessing a KANK1-NTRK3 gene fusion experienced tumor progression and clinical deterioration with conventional chemotherapeutics. Upon initiation of Entrectinib treatment she experienced rapid clinical improvement, with significant partial response and sustained decrease in tumor markers.

Evaluation of Outcomes of Mucinous Ovarian Cancer Treated at a Tertiary Care Cancer Hospital in Pakistan.

Syed Abdul Mannan HamdaniObjective To evaluate the clinicopathological features and survival outcomes of mucinous ovarian cancer (MOC) patients in an Asian population. Study Design Descriptive observational study. Place and Duration of Study Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, from January 2001 to December 2016. Methods Data of MOC were evaluated for demographics, tumor stage, clinical characteristics, tumor markers, treatment modalities, and outcomes from electronic Hospital Information System. Results Nine-hundred patients with primary ovarian cancer were reviewed, out of which 94 patients (10.4%) had MOC. The median age was 36 ± 12.4 years. The most common presentation was abdominal distension 51 (54.3%), while the rest presented with abdominal pain and irregular menstruation. Using FIGO (The International Federation of Gynecology and Obstetrics) staging, 72 (76.6%) had stage I, 3 (3.2%) stage II, stage III in 12 (12.8%), and 7 (7.4%) had stage IV disease. The majority of patients 75 (79.8%) had early-stage (stage I/II), while 19 (20.2%) presented with advanced-stage (III & IV). The median follow-up duration was 52 months (range 1-199 months). Among patients with early-stage (I&II), 3- and 5-year progression-free survival (PFS) was 95%, while for advanced stage (III&IV), PFS was 16% and 8%, respectively. The overall survival (OS) in early-stage I&II was 97%, while for advanced stages III & IV, the OS was 26%. Conclusion MOC is a challenging and rare subtype of ovarian cancer requiring special attention and recognition. Most patients treated at our center presented with early stages and had excellent outcomes, while advanced-stage disease had dismal results.

Development and validation of a nomogram to predict cancer-specific survival of mucinous epithelial ovarian cancer after cytoreductive surgery.

BACKGROUND: Mucinous epithelial ovarian cancer (mEOC) is a relatively uncommon subtype of ovarian cancer with special prognostic features, but there is insufficient research in this area. This study aimed to develop a nomogram for the cancer-specific survival (CSS) of mEOC based on Surveillance, Epidemiology, and End Results (SEER) database and externally validate it in National Union of Real World Gynecological Oncology Research and Patient Management (NUWA) platform from China. METHODS: Patients screened from SEER database were allocated into training and internal validation cohort in a ratio of 7: 3, with those from NUWA platform as an external validation cohort. Significant factors selected by Cox proportional hazard regression were applied to establish a nomogram for 3-year and 5-year CSS. The performance of nomogram was assessed by concordance index, calibration curves and Kaplan-Meier (K-M) curves. RESULTS: The training cohort (n = 572) and internal validation cohort (n = 246) were filtered out from SEER database. The external validation cohort contained 186 patients. Baseline age, tumor stage, histopathological grade, lymph node metastasis and residual disease after primary surgery were significant risk factors (p < 0.05) and were included to develop the nomogram. The C-index of nomogram in training, internal validation and external validation cohort were 0.869 (95% confidence interval [CI], 0.838-0.900), 0.839 (95% CI, 0.787-0.891) and 0.800 (95% CI, 0.738-0.862), respectively. The calibration curves of 3-year and 5-year CSS in each cohort showed favorable agreement between prediction and observation. K-M curves of different risk groups displayed great discrimination. CONCLUSION: The discrimination and goodness of fit of the nomogram indicated its satisfactory predictive value for the CSS of mEOC in SEER database and external validation in China, which implies its potential application in different populations.

Durable remission in a patient with ERBB2-amplified recurrent mucinous ovarian carcinoma treated with Trastuzumab-Carboplatin-Paclitaxel.

Patients with advanced stage or recurrent mucinous ovarian carcinoma exhibit poor response to standard platinum- and taxane-based chemotherapy and poor prognosis. We report a 29-year-old patient with recurrent ERBB2-amplified mucinous ovarian carcinoma (with expansile growth pattern at initial diagnosis and previously treated with adjuvant capecitabine/oxaliplatin) who underwent optimal secondary cytoreduction followed by 6 cycles of carboplatin/paclitaxel/trastuzumab and 1-year maintenance trastuzumab. This patient remains without radiologic or biochemical evidence of disease for more than 3 years after secondary cytoreduction. This case supports routine assessment of HER2 status in patients with advanced or recurrent mucinous ovarian carcinoma and highlights the potential of HER2-targeted therapy with trastuzumab in combination with standard carboplatin and paclitaxel in this disease. This case also raises the possibility that expansile mucinous ovarian carcinomas with ERBB2 amplification and p53 mutant immunohistochemical staining pattern (as this patient had) may be associated with a more aggressive behavior and higher risk of relapse.