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Introduction: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice. Material and methods: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I‐III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard. Results: In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively. Conclusions: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI. [ABSTRACT FROM AUTHOR]

More effective treatments are needed for low-grade serous ovarian carcinoma (LGSOC). Our patient, who suffers from metastatic LGSOC, had received all established treatments. Sequencing analysis revealed an activating BRAF mutation. Therefore, combined treatment with BRAF and MEK inhibitors, which is the gold standard in malignant melanoma, was initiated. After eight months of therapy, the response was assessed as complete and the treatment is still, 3.5 years after initiation, of benefit. To our knowledge, no complete response on combined BRAF and MEK inhibitor treatment of low-grade serous ovarian cancer has previously been reported. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010–2017 with FIGO stages I–III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69–8.07, p <.001) followed by deep myometrial invasion (RR = 1.64, CI 1.13–2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03–29.10,) and non-diploidy (EMR = 3.23, CI 1.25–8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05–5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important. [ABSTRACT FROM AUTHOR]

Background:The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer. Method:This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009–2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations. Results:Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n = 51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n = 195) or other/multiple (n = 187) distant metastases (p = .0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99,p = .001) or other/multiple distant sites (HR 2.67,p = .007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p = .245). Conclusion:Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients. [ABSTRACT FROM AUTHOR]

Aim:The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC). Method:A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearson’s correlation coefficient and Cohen´s kappa coefficient. Results:The completeness was 95%. The timeliness was 88–91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearson’s correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70–81%; kappa 0.49) and type of primary treatment 90% (95% CI 87–94%; kappa 0.85) in OC and in EC 88% (95% CI 84–93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68–80%; kappa 0.69) and 87% (95% CI 82–91%; kappa 0.79), respectively. Conclusions:The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results. [ABSTRACT FROM AUTHOR]

Background. A number of chemotherapeutic drugs are active in epithelial ovarian cancer (EOC) but so far choice of drugs for treatment is mostly empirically based. Testing of drug activity in tumour cells from patients might provide a rationale for a more individualised approach for drug selection. Material and methods. Sensitivity of EOC to chemotherapeutic drugs was analysed in 125 tumour samples from 112 patients using a short-term primary culture assay based on the concept of total cell kill. Sensitivity was related to tumour histology, treatment status and clinical tumour response. Results. For most EOC standard drugs serous high grade and clear cell EOC were the most sensitive subtypes and the mucinous tumours the most resistant subtype. Docetaxel, however, tended to show the opposite pattern. Samples from previously treated patients tended to be more resistant than those from treatment naïve patients. The activity of cisplatin correlated with that of other drugs with the exception of docetaxel. Tumour samples from two sites in the same patient at the same occasion showed similar cisplatin sensitivity in contrast to samples taken at different occasions. Samples from patients responding in the clinic to treatment were more sensitive to most drugs than samples from non-responding patients. At the individual patient level, drug sensitivity in vitro compared with clinical response showed sensitivities and specificities in the 83-100% and 55-83% ranges, respectively. Conclusions. Assessment of EOC tumour cell drug sensitivity in vitro provides clinically relevant and potentially useful information for the optimisation of drug treatment. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The single-arm OCTAVIA study evaluated front-line bevacizumab plus weekly paclitaxel and q3w carboplatin. Patients and methods: Patients with newly diagnosed ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] stage IIb–IV or grade 3/clear-cell stage I/IIA) received bevacizumab (7.5mg/kg, day 1), weekly paclitaxel (80mg/m2 days 1, 8, 15) and carboplatin (area under the curve 6 [AUC6], day 1) intravenously q3w for 6–8 cycles, followed by single-agent bevacizumab (total 1year). The primary objective was to demonstrate median progression-free survival (PFS)>18months according to the lower 90% confidence limit. Secondary end-points included objective response rate, overall survival, safety and tolerability. Results: Most (74%) of the 189 treated patients had stage IIIC/IV disease, similar to the ICON7 population. Patients received a median of six chemotherapy and 17 bevacizumab cycles. At the predefined cutoff 24months after last patient enrolment, 99 patients (52%) had progressed and 19 (10%) had died, all from ovarian cancer. Median PFS was 23.7months (95% confidence interval [CI], 19.8–26.4months), 1-year PFS rate was 85.6%, Response Evaluation Criteria in Solid Tumors (RECIST) response rate was 84.6% and median response duration was 14.7months. Most patients (⩾90%) completed at least six chemotherapy cycles. Grade ⩾3 peripheral sensory neuropathy occurred in 5% and febrile neutropenia in 0.5%. Grade ⩾3 adverse events typical of bevacizumab were no more common than in phase III bevacizumab ovarian cancer trials. There was one case of gastrointestinal perforation (0.5%) and no treatment-related deaths. Conclusion: OCTAVIA met its primary objective, demonstrating median PFS of approximately 2years. This bevacizumab-containing regimen is active and tolerable. [Copyright &y& Elsevier]

Introduction: Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled. Methods: Patients (n =540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I–III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy. Results: In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41–0.99; P =0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44–0.89; P =0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46–1.03; P =0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35–0.88; P =0.01). Conclusion: Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results. [Copyright &y& Elsevier]

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in developed countries. Several promising steps toward individualized therapy have been taken recently due to increased knowledge of molecular biology. Multidisciplinary conferences for treatment planning and the centralization to tertiary surgical centers improve quality of surgery and survival. The primary treatment of EOC is radical surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel. Bevacizumab added to the chemotherapy and used as maintenance treatment is standard in the primary treatment of patients with residual tumor or inoperable patients. The PARP inhibitor olaparib is recommended as maintenance treatment of women with platinum sensitive relapsed BRCA mutated high-grade serous EOC who have responded to platinum-based chemotherapy. BRCA testing should be offered to women with EOC. In platinum-resistant recurrence addition of bevacizumab to chemotherapy should be considered.