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Introduction: Our objective was to investigate the trajectories of anxiety, depression, emotional and social functioning in women with newly diagnosed vulvar cancer from the time of diagnosis to 12 months after treatment. A further aim was to identify risk factors for high levels of anxiety.Material and methods: PROVE (PROspective Vulvar Cancer Evaluation) is a nationwide longitudinal cohort study investigating quality of life in women with newly diagnosed vulvar cancer by the following validated patient-reported outcome measures at diagnosis, and 3 and 12 months after treatment: The Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Vulvar module VU34. Mean scores, changes over time and associations were analyzed by generalized estimated equations and log-linear regression models, adjusted for possible confounders.Results: Between 2019 and 2021, 105 (69%) women completed the questionnaires at all three time points. At diagnosis, 42% of the women reported elevated anxiety levels, decreasing significantly to 30% during the first 12 months. Insomnia, persisting vulvar symptoms and high information needs were significantly associated with a high level of anxiety (relative risk [RR] 2.1, 95% CI 1.2-3.7 for insomnia; RR 2.8, 95% CI 1.7-4.6 for vulvar symptoms, RR 2.7, 95% CI 1.5-4.9 for information needs). We found a trend towards a higher level of anxiety in younger women (<65 years: RR 1.5, 95% CI 1.0-2.5). Participants reported a low and stable prevalence of depression (14%) and high social functioning throughout the study period.Conclusions: Women with newly diagnosed vulvar cancer report a high level of anxiety at diagnosis. Despite a significant improvement, anxiety remains widely prevalent during the first year of follow-up. Targeting insomnia, vulvar symptoms and unmet needs m, Funding Agencies|We would like to thank Johan Zetterqvist from the Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, for his invaluable statistical support. Furthermore, we thank Perihan Inekci from the Clinical Trials Office at; Department of Learning, Informatics, Management and Ethics, Karolinska Institutet

Objective The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). Methods Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008–2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. Results In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0–21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0–21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. Conclusions For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS.

Objective. To describe the baseline symptom burden(SB) experienced by patients(pts) with recurrent ovarian cancer(ROC) prior and associations with progression free survival (PFS) and overall survival (OS). Methods. We analysed baseline SB reported by pts. with platinum resistant/refractory ROC (PRR-ROC) or potentially-platinum sensitive ROC receiving their third or greater line of chemotherapy (PPS-ROC >= 3) enrolled in the Gynecologic Cancer InterGroup - Symptom Benefit Study (GCIG-SBS) using the Measure of Ovarian Symptoms and Treatment concerns (MOST). The severity of baseline symptoms was correlated with PFS and OS. Results. The 948 pts. reported substantial baseline SB. Almost 80% reported mild to severe pain, and 75% abdominal symptoms. Shortness of breath was reported by 60% and 90% reported fatigue. About 50% reported moderate to severe anxiety, and 35% moderate to severe depression. Most (89%) reported 1 or more symptoms as moderate or severe, 59% scored 6 or more symptoms moderate or severe, and 46% scored 9 or more symptoms as moderate or severe. Higher SB was associated with significantly shortened PFS and OS; five symptoms had OS hazard ratios larger than 2 for both moderate and severe symptom cut-offs (trouble eating, vomiting, indigestion, loss of appetite, and nausea; p < 0.001). Conclusion. Pts with ROC reported high SB prior to starting palliative chemotherapy, similar among PRR-ROC and PPS-ROC >= 3. High SB was strongly associated with early progression and death. SB should be actively managed and used to stratify patients in clinical trials. Clinical trials should measure and report symptom burden and the impact of treatment on symptom control. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http, Funding Agencies|NHMRC [1063012, 570893]; Target Ovarian Cancer [UCL-P001AL]; Cancer Research UK and UCL Cancer Trials Centre [C444/A15953]; Australian Government through Cancer Australia; Department of Health

Purpose: Neuropathy is the dose-limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for interindividual differences remain unexplained. In this study, we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes. Experimental Design: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics, and 30 Charcot–Marie–Tooth genes, in 228 cancer patients with no/low neuropathy or high-grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/gene-based analyses were used to compare variant frequencies among neuropathy groups, and Cox regression models were used to analyze neuropathy along treatment. Results: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low-frequency nonsynonymous variants in EPHA6 were present exclusively in patients with high neuropathy, and all affected the ligand-binding domain of the protein. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency nonsynonymous variant carriers [HR, 14.60; 95% confidence interval (CI), 2.33–91.62; P ¼ 0.0042], and an independent cohort confirmed an increased neuropathy risk (HR, 2.07; 95% CI, 1.14–3.77; P ¼ 0.017). Combining the series gave an estimated 2.5-fold higher risk of neuropathy (95% CI, 1.46–4.31; P ¼ 9.1 10 4). Conclusions: This first study sequencing EPHA genes revealed that low-frequency variants in EPHA6, EPHA5, and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHA's neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs., Depto. de Enfermería, Fac. de Enfermería, Fisioterapia y Podología, TRUE, pub

Background We explored the impact of persistent sensory and motor taxane-induced peripheral neuropathy (TIPN) symptoms on health-related quality of life (HRQL) among early-stage breast cancer survivors (ESBCS). Methods A population-based cohort of 884 residual-free ESBCS received a postal questionnaire, including the EORTC chemotherapy-induced PN (CIPN20) and the EORTC QLQ-C30 instruments. Mean scores of QLQ-C30 scales among ESBCS with and without TIPN were calculated and adjusted for confounding factors (age, lifestyle factors, co-morbidities; linear regression analyses). Interpretation of QLQ-C30 results were based on guidelines. Results Response rate was 79%, and 646 survivors were included in the analysis. In median, 3.6 (1.5-7.3) years had elapsed post-taxane treatment. All TIPN symptoms had a significant impact on global QoL, which worsened with increased severity of TIPN. Between 29.5% and 93.3% of ESBCS with moderate-severe TIPN reported a clinical important impairment of functioning and personal finances, 64.3-85.7% reporting "difficulty walking because of foot drop," and 53.1-81.3% reporting "problems standing/walking because of difficulty feeling ground under feet" had impaired functioning/finances. The difference in mean scores between affected and non-affected survivors was highest for "numbness in toes/feet" and "difficulty walking because of foot drop." Moderate-severe "difficulty climbing stairs or getting out of chair because of weakness of legs" and "problems standing/walking because of difficulty feeling ground under feet" were associated with the largest clinically important differences on all scales. Conclusion Persistent sensory and motor TIPN is associated with clinically relevant impairment of global QoL, functioning, and personal finances among ESBCS, which increased with level of TIPN severity., Funding Agencies|Linkoping University; Swedish Cancer Society [190224]; Medical Research Council of Southeast Sweden [FORSS-932359]; FuturumThe Academy for Health and Care, Jonkoping County Council [575361]; Forsknings-ALF [LIO-901261]

Objective The Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory recurrent ovarian cancer (PRR-ROC) and potentially platinum sensitive with >= 3 lines of chemotherapy (PPS-ROC >= 3). Methods Participants completed the Measure of Ovarian Cancer Symptoms and Treatment (MOST) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 questionnaires at baseline and every 3-4 weeks until progression. Participants were classified symptomatic if they rated >= 4 of 10 in at least one-third of symptoms in the MOST index. Improvement in MOST was defined as two consecutive scores of <= 3 in at least half of the symptomatic items at baseline. Improvement in HRQL was defined as two consecutive scores >= 10 points above baseline in the QLQ-C30 summary score scale (range 0-100). Results Of 948 participants enrolled, 910 (96%) completed baseline questionnaires: 546 with PRR-ROC and 364 with PPS-ROC >= 3. The proportions of participants symptomatic at baseline as per MOST indexes were: abdominal 54%, psychological 53%, and disease- or treatment-related 35%. Improvement was reported in MOST indexes: abdominal 40%, psychological 35%, and disease- or treatment-related 38%. Median time to improvement in abdominal symptoms occurred earlier for PRR-ROC than for PPS-ROC >= 3 (4 vs 6 weeks, p=0.044); median duration of improvement was also similar (9.0 vs 11.7 weeks, p=0.65). Progression-free survival was longer among those with improvement in abdominal symptoms than in those without (median 7.2 vs 2.5 months, p<0.0001). Improvements in HRQL were reported by 77/448 (17%) with PRR-ROC and 61/301 (20%) with PPS-ROC >= 3 (p=0.29), and 102/481 (21%) of those with abdominal symptoms at baseline. Conclusion Ove, Funding Agencies|NHMRCNational Health and Medical Research Council of Australia [1063012, 570893]; Target Ovarian Cancer [UCL-P001AL]; Cancer Research UKCancer Research UK; UCL Cancer Trials Centre [C444/A15953]; Australian Government through Cancer AustraliaAustralian Government; NHMRC Program grantNational Health and Medical Research Council of Australia; Department of HealthEuropean Commission

Background Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. Material and methods In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). Results Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. Conclusions Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis., Funding Agencies|Swedish Cancer SocietySwedish Cancer Society; Scientific Council of the Region Halland

Background: Research focusing on patients’ perceptions of the quality of gynecological cancer care is needed. Objective: To adapt the Quality from the Patient’s Perspective instrument for use in gynecological cancer care (QPP-GynCa) and describe patients’ perceptions of their quality of care in terms of the care received and the subjective importance of the aspects of care. Methods: A cross-sectional study 6–8 months after diagnosis was conducted, involving 1511 patients (response rate of 50.4%) included in the Swedish quality registry for gynecologic cancer. Results: The exploratory factor analysis (n = 1431) resulted in the QPP-GynCa with a 5-factor structure and an eigenvalue of ≥1, explaining 73.1% of the total scale variance. The final 27-item version of the QPP-GynCa consisted of 18 items with 8 additional single items and 1 global single item. The Cronbach’s alpha was acceptable for most factors (>.80). Subjective importance scores were higher than corresponding quality of care scores for care received (P ≤ .01)in all dimensions, factors, and items. Conclusions: The QPP-GynCa instrument reflects all 4 dimensions of the theoretical model of quality of care and achieved good validity as a reliable instrument in assessing the quality of gynecological cancer care. Implication for Practice: Information related to self-care, aspects of sexuality, and reducing patient waiting times need improvement. What Is Foundational: This study contributes to a better understanding of quality of gynecological cancer treatment and care. The validated QPP-GynCa instrument will be a platform for more research on how this group of patients experience their received care, as well as importance of each aspect of care.

Purpose. The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). Method. A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end -of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. Results. Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning do-mains and worse overall health at both time points. Conclusion. Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical prac-tice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research. (c) 2022 Elsevier Inc. All rights reserved., Funding Agencies|NHMRC, Australia [1063012, 570893]; Target Ovarian Cancer [UCL-P001AL]; Cancer Research UK; UCL Cancer Trials Centre [C444/A15953]; NHMRC program [APP1092856]; Australian Government through Cancer Australia; NHMRC Program; Department of Health

Introduction Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long-term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately. Material and Methods The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997-2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow-up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow-up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis. Results In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow-up time of 7.1 years (interquartile range 3.1-13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population-based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03-0.53) after EA and 1.27 (95% CI 0.86-1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, r, Funding Agencies|Swedish Cancer Society

Objective. To examine the patterns of recurrence and how these patterns are associated with survival in vulvar squamous cell carcinoma. We also explored the survival impact of surgical groin staging (SGS). Methods. Nationwide population-based study including women diagnosed with vulvar squamous cell carcinoma between 2012 and 2015 and registered in the Swedish Quality Registry for Gynecologic Cancer. Cumulative incidence rates (CIR), recurrence-free (RFS) and overall survival (OS) were calculated by Kaplan Meier estimates. The impact of SGS on RFS and OS was analyzed by proportional hazards models. Results. 489 eligible women were included. Median follow-up time was 64 months. The overall recurrence rate was 22.3%. Site of recurrence: local in 61.0%, groin in 30.0%, distant in 9.0%. The CIR for local recurrences increased with time (5.9% at 2-years, 14.7% at 5-years) while the rate of groin and distant recurrences was nearly steady (5.5% to 6.3% and 1.5% to 1.7%, respectively). Median 2-year and 4-year OS post-recurrence was 57.8% and 37.4% for local, 17.2%, 10.3% for groin and 0% for distant recurrences, respectively. SGS was omitted in 23.7% of surgically treated women with FIGO stages IB-II and significantly associated with worse RFS (Hazard ratio, HR, 1.9; 95%CI, 1.0-3.5; p = 0.04) and OS (HR 2.0; 95%CI, 1.1-3.8; p = 0.04) after adjustment for age, FIGO stage, tumor size, resection margins and performance status. Conclusion. The cumulative incidence of isolated vulvar recurrence was low but for those affected the prognosis was poor. Surgical groin staging is a crucial part of primary treatment and should not be omitted. (c) 2021 Published by Elsevier Inc., Funding Agencies|Swedish Society for Gynecologic Cancer

BACKGROUNDThe majority of patients with newly diagnosed metastatic prostate cancer (PC) initially respond to androgen deprivation therapy (ADT) and are classified as metastatic castration-sensitive PC (mCSPC). Following months to years of ADT, the disease tends to become resistant to ADT. Recent randomized phase-III trials demonstrated a survival benefit with the addition of upfront docetaxel to ADT in mCSPC. Following its implementation in routine care, this combined treatment strategy requires more detailed evaluation in a real-world setting.AIMTo assess the real-world outcome and safety of upfront docetaxel treatment in mCSPC.METHODSA multicenter retrospective cohort study in the Southeast Health Care Region of Sweden was performed. This region includes approximately 1.1 million citizens and the oncology departments of Linkoping, Jonkoping, and Kalmar. All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included. The primary endpoint was progression-free survival (PFS) at 12 mo, and the secondary endpoints were PFS at 24 mo, overall survival (OS), treatment intensity, adverse events, and unplanned hospitalizations. Exploratory analyses on potential prognostic parameters were performed.RESULTSNinety-four patients were eligible and formed the study cohort. PFS at 12 and 24 mo was 75% (95%CI: 66-84) and 58% (46-70), respectively. OS at 12 and 24 mo was 93% (87-99) and 86% (76-96). A total of 91% of patients (n = 86) were given docetaxel according to the standard protocol of 75 mg/m(2) every 3 wk (6 cycles), while 9% (n = 8) received a modified protocol of 50 mg/m(2) every 2 wk (9 cycles). The average overall dose intensity for those commencing standard treatment was 91%. Univariate Cox regression analyses show that baseline PSA > 180 vs < 180 and the presence of distant metastases vs locoregional lymph node metastases were only negative prognostic factors (HR 2.86, 95%CI: 1.39-5.87, P = 0.0041 and 3.36, 95%CI: 1.03-10

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.

Background The aim of this study was to analyze overall survival in endometrial cancer patients’ FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). Methods A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. Results In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18–1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95–1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. Conclusion The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

Aim: The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation. Method: Women with primary epithelial ovarian cancer, FIGO stage IIIC?IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008?2011 and 2013?2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated. Results: In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013?2016 vs. 2008?2011 (EMRR 0.89; 95%CI:0.82?0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95% CI:26.8?32.8) vs. 37.4% (95%CI:33.6?41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8?39.2) to 43 months (95%CI,40.9?46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%,ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19 & ndash;1.47, p < 0.001) for NACT+IDS and 3.00 (95% CI,2.66 & ndash;3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age <= 70 years, and stage IIIC were found to be independent factors for improved RS. Conclusion: Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer.

OBJECTIVE: Pre-clinical studies have identified marker- and tumor compartment-defined functionally distinct macrophage subsets. Our study analyzes marker-defined macrophage subsets in different tumor compartments of high-grade serous ovarian cancer (HGSC). METHODS: A discovery cohort (N = 113) was subjected to immunohistochemistry (IHC) analyses. CD68-positivity was confirmed for CD11c-, CD80- and CD163-positive cells. Subset-marker-positive cells were scored in the total tumor and in four tumor compartments. Correlation analyses investigated co-expression of subsets, relationship to CD8+ cells and survival associations. A validation cohort (N = 121) was used to confirm selected findings from the discovery cohort. RESULTS: CD163-positve cells was the most abundant subtype in all compartments. CD11c and CD163 subsets were strongly correlated with each other in stroma and epithelial areas, whereas CD80 and CD163 were correlated in epithelial areas. CD80 and CD11c in perivascular areas showed low correlations. Strong associations were detected between CD8 and CD80 in the tumor epithelium-dominated areas, and between CD8 and CD11c in stroma areas. High stromal CD11c density was associated with a longer median overall survival in the discovery cohort (HR 0.39; CI 95%, 0.23-0.68; p = 0.001) and in the validation cohort (HR 0.46; CI 95%, 0.22-0.93; p = 0.03). CONCLUSIONS: Our study supports the existence of clinically relevant marker- and localization defined macrophage subsets in HGSC, which are independently regulated. Moreover, it suggests stromal CD11c as a novel prognostic marker in HGSC.

Background: While recent randomised phase III trials show that trifluridine/tiperacil (TAS-102) may prolong life in patients with refractory metastatic colorectal cancer (rmCRC), palliative aspects on its efficacy and tolerability in real world patients need further elucidation. Methods: A retrospective observational multicentre study was designed, including all patients with rmCRC who received TAS-102 under 2016-2019 in the South East Health Care region of Sweden. 48 patients were identified. Primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), time to ECOG performance status deterioration (PSD), safety and dose reductions, admission to and duration of access to palliative care, and administration of TAS-102 in the last 30 days before death. Results: Median OS, PFS, and time to PSD (a proxy for impaired quality of life) from start of TAS-102 were 6.4 months (95% CI: 4.4-8.4), 2.3 months (95% CI: 1.8-2.7) and 2.5 months (95% CI: 1.9-3.2), respectively. Following uni- and multivariable regression analyses, the number of previous treatment lines (<= 2 vs. >= 3) was statistically independent for OS (median 7.8 vs. 5.3 months, P=0.05), PFS (median 2.4 vs. 1.8 months, P=0.03), and time to PSD (median 2.8 vs. 1.8 months, P=0.03). Thirty-four (71%) of the patients received reduced doses. The most common grade 3-4 toxicity was neutropenia (39%). Forty-three (90%) were admitted to GP or hospital-based home palliative care. Median time for access to any form of palliative care before death was 2.3 (95% CI: 0.5-3.2) months. Few patients (n=3, 7%) received their last dose of TAS-102 in their last 30 days of life. Conclusions: The outcome and tolerability of TAS-102 in rmCRC appear similar in a real-world context and randomised trials. The retrospective design and limited sample size preclude firm conclusions on subgroup analyses, but it appears that the prognosis is slightly better the earlier TAS-102 is introduced, Funding Agencies|ALF grants Region Ostergotland [LIO-697991, LIO-707011, LIO-697461]; CKOC grants Region Ostergotland; Department of Oncology at Ryhov County Hospital, Jonkoping, Sweden

Background: The outcome and tolerability of palliative second line chemotherapy for advanced pancreatic cancer (APC) in real life patients are largely unknown. Prognostic parameters for risk stratification and treatment guidance are lacking. Materials and Methods: A population based multicenter retrospective cohort study was conducted, covering all APC patients who received palliative second-line chemotherapy between 2011 and 2018 at any cancer center in the South East Region of Sweden. Primary outcome was overall survival after second-line therapy (OS2). Time to treatment failure after second-line therapy (TTF2), hematological toxicity, and unplanned hospitalizations were key secondary outcomes. A number of baseline potentially prognostic parameters were assessed. Results: A total of 509 patients received first-line palliative chemotherapy, and of these 167 (33%) received at least one dose of second-line therapy and formed the final study population. Median OS2 was 5.2 months (95% CI = 4.7–5.7) and median TTF2 was 1.9 months (1.5–2.2). OS2 and TTF2 were similar regardless regimen, including comparison of the two most common regimens (fluoropyrimidine monotherapy vs. fluoropyrimidine/oxaliplatin doublet). Multivariate analysis revealed that normal plasma albumin (≥35) and serum CA-19-9 above median (>1,550) were independent predictors for OS2 (HR = 0.21, p < 0.001 and HR = 2.03, p = 0.009) and TTF2 (HR = 0.22, p < 0.001 and HR = 2.03, p = 0.01), while ECOG performance status >1 was predictive for TTF2 (HR = 2.05, p = 0.032). Grade 3–4 hematological toxicity was registered in 17 patients (10%). 50 (30%) had at least one event of hospitalization. Conclusion: The real world outcome of second line palliative chemotherapy for refractory APC remains dismal. Baseline plasma albumin, serum CA-19-9, and performance status emerge as key prognostic factors, and should be further studied as tools for individualized treatment decisions., Funding Agencies|Futurum, Academy for Health and Care Jonkoping County Council [695491]; Medical Research Council of Southeast Sweden [FORSS-751541]; ALF grants Region Ostergotland [LIO-697991, LIO-707011, LIO-697461]; Sveriges Gastro-Onkologiska Forening (GOF); CKOC grants Region Ostergotland

Objective: Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group. Methods: A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort. Results: Median follow-up time was 41 months. The study population included 657 women; 33% were >= 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women >= 80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women >= 80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III. Conclusions: In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden ad-hered to guidelines. Areas of improvement include treatment for stage II and for the very old.

Endometrial cancer is the most common malignancy of the female genital tract in the more developed regions of the world [1]. Stage of disease, i.e., the extent of tumor spread at the time of presentation, is the most significant prognostic parameter.

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.

Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p < 0.001). In stage IIA1 74% had CTRL, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p < 0.001). Stages III-IVA; <40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p < 0.001). RS stage IVB 7%. Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy. (C) 2019 Elsevier Inc. All rights reserved.

BACKGROUND: Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial.MATERIALS AND METHODS: In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D).RESULTS: Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21.CONCLUSIONS: There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned.

Aim of the study: Endocrine treatment (ET) is an alternative as salvage therapy in epithelial ovarian cancer (EOC) but the usage in routine care is unknown. We evaluated the treatment patterns and outcome of patients receiving ET for EOC in the Southeast medical region in Sweden.Method: Patients were identified through the population-based Southeast Quality Registry for gynaecological cancer. Inclusion criteria were: age 18 years, histologically verified EOC diagnosed 2000-2013, ET for 4 weeks. Coverage compared with the Swedish National Cancer Registry was 100%. Data extracted from medical records was collected by means of a study-specific Case Report Form. Last date of follow-up was February 1st, 2018. All statistics were descriptive.Results: Altogether 248 (18%) of 1414 patients were treated with ET. Most (49%) had received only one, and 34% two previous lines of chemotherapy. Time from last chemotherapy to ET was 4 months, range 0-55months. The reason for initiating ET was tumor progression (66%), chemotherapy related toxicity (29%) and maintenance (4%). Tamoxifen was prescribed in 94% of cases. Best response was partial (amp;lt; 5%) and stable disease (50%). No patient had a complete response. 194 (78%) patients received subsequent chemotherapy, of these 27% had 3-7 lines of chemotherapy. Duration of ET was a median 4 months (range 1-80 months). Median time from ET to subsequent chemotherapy was 5 months (range 0-79). The median overall survival was 45 months (range 9-173).Conclusion: In the Southeast region of Sweden, endocrine treatment for EOC was prescribed inconsistently and in various settings, usually initiated by a rising CA-125 level. Poorer documentation and irregular tumor response assessment were observed for endocrine treatment compared to chemotherapy., Funding Agencies|Medical Research Council of Southeast Sweden; ALF Grants, Region Ostergotland

Background and Objectives In the Robot Assisted Surgery for High Risk Endometrial Cancer (RASHEC) trial, patients with high-risk endometrial cancer were randomly assigned to robot-assisted laparoscopic surgery (RALS) or laparotomy for pelvic and infrarenal para-aortic lymph node dissection. We here report on self-reported lower limb lymphedema (LLL), lymphocyst formation, ascites, and long-term serious adverse events 12 months after surgery. Patients and methods Patients were enrolled between 2013 and 2016, and 96 patients were included in the per protocol analysis, evenly distributed between RALS and laparotomy. Self-reported LLL was recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for endometrial cancerEN24, assessed before and 12 months after surgery. Computed tomography was assessed at baseline, 3, and 12 months. Medical charts were reviewed for serious adverse events and hospital admissions 31 to 365 days after surgery. Results At 12 months after laparotomy and RALS, 61% and 50% patients, respectively, reported LLL (p = 0.31). In univariate analysis, the mean score of LLL at 12 months was significantly higher for laparotomy than for RALS (p amp;lt; 0.05) and for those without abdominal drainage (p = 0.02), but was not independently associated with LLL in the multivariate analysis. Imaging showed no significant difference in lymphocyst formation or ascites between surgical modalities. No difference was found in serious adverse events and admissions to hospital for any reason. There was no agreement between lymphocyst formation or ascites and self-reported LLL. Conclusion Follow-up 1 year after comprehensive surgical staging for high-risk endometrial cancer showed no differences in self-reported LLL, findings on imaging, or SAE between laparotomy and robot-assisted surgery.

Objective. Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. Methods. Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. Results. Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. Conclusions. Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted. (C) 2018 Published by Elsevier Inc.

Background Platinum-based chemotherapy is the foundation of treatment for platinum-sensitive recurrent ovarian cancer, but has substantial toxicity. Bevacizumab and maintenance poly(ADP-ribose) polymerase (PARP) inhibitors both significantly improve efficacy versus standard therapy, primarily in terms of progression-free survival, and offer the potential for chemotherapy-free treatment. AVANOVA2 compared niraparib and bevacizumab versus niraparib alone as definitive treatment for platinum-sensitive recurrent ovarian cancer. Methods This open-label, randomised, phase 2, superiority trial in 15 university hospitals in Denmark, Sweden, Finland, Norway, and the USA enrolled women aged 18 years or older with measurable or evaluable high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, and had to have previously received platinum-containing therapy for primary disease but amp;lt;= 1 prior non-platinum-containing regimen for recurrent disease. Previous treatment with bevacizumab or first-line maintenance PARP inhibitors was permitted. Eligible patients were randomly assigned 1:1 (by random permuted blocks with block sizes of two and four, no masking), stratified by homologous recombination deficiency status and chemotherapy-free interval, to receive once-daily oral niraparib 300 mg alone or with intravenous bevacizumab 15 mg/kg once every 3 weeks until disease progression. The primary endpoint was progression-free survival, assessed by the investigators in the intention-to-treat population after events in at least 62 patients. Safety was analysed in all patients who received at least one dose of study drug. This ongoing trial is registered with ClinicalTrials.gov , number NCT02354131. Findings Between May 23,2016, and March 6,2017,97 patients were enrolled and randomly assigned: 48 to niraparib plus bevacizumab and 49 to single-agent niraparib. Median follow-up wa, Funding Agencies|Nordic Society of Gynaecological Oncology; Tesaro

Background Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial. Materials and methods In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D). Results Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21. Conclusions There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned., Funding Agencies|Tesaro Inc.; NSGO

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.

BACKGROUND: Modified Glasgow Prognostic Score (mGPS) is predictive of survival in many advanced cancers, but has not been evaluated in recurrent ovarian cancer (ROC). The aim was to determine validity of mGPS in ROC, investigate its associations with health related quality of life (HRQL) and ECOG performance status (PS). METHODS: mGPS is based on serum C reactive protein (CRP) and albumin, with scores ranging from 0 (least) to 2 (most). HRQL was measured with EORTC QLQ C-30 and OV-28. χ2 tests for trend were used to examine the relationship between HRQL, PS and mGPS. Cox proportional hazards regression was used to assess associations between mGPS, HRQL, clinicopathological factors, and overall survival (OS). RESULTS: Inflammatory markers were available in 516 of 948 patients in GCIG SBS. 200(39%) had potentially platinum sensitive ROC with ≥3 lines of chemotherapy, 316(61%) had platinum resistant ROC. 282(55%), 123(24%), 111(22%) had mGPS of 0, 1, 2, respectively. Median OS (months) was 18.1, 9.6, and 6.6 for mGPS 0, 1, and 2 respectively. mGPS was an independent predictor of OS after adjusting for PS and platinum sensitivity (p<0.001). mGPS remained a predictor of OS after adjusting for physical function, role function, global health status, abdominal/GI symptoms, and multiple clinicopathologic factors (p=0.02). Worse PS and higher mGPS were associated with poorer HRQL (p<0.001). Higher mGPS was associated with worse HRQL, independent of PS. CONCLUSION: The mGPS is an independent predictor of OS in ROC after adjusting for HRQL and clinicopathological factors. Higher mGPS is associated with worse HRQL independent of PS. mGPS is simple, inexpensive and may be suitable for clinical practice, clinical trial patient selection and stratification.

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 Pearsons correlation coefficient and Cohens 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 Pearsons 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., Funding Agencies|Swedish Association of Local Authorities and Regions; Swedish Cancer Society

IntroductionWomen with cervical cancer in the Nordic countries are increasingly undergoing pretreatment imaging by ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) or computed tomography, or sentinel lymph node procedure. The present survey reports the influence of pretreatment imaging findings on the recorded clinical International Federation of Gynecology and Obstetrics (FIGO) stage in Nordic countries and its impact on treatment planning and preferred surgical approach in cervical cancer. Material and methodsThe Nordic Society of Gynecological Oncology Surgical Subcommittee developed a questionnaire-based survey that was conducted from 1 January to 31 March 2017. All the 22 Nordic Gynecological Oncology Centers (Denmark 5, Finland 5, Iceland 1, Norway 4, and Sweden 7) were invited to participate. ResultsThe questionnaires were returned by 19 of 22 (86.3%) centers. The median number (range) of women with cervical cancer treated at each center annually was 32 (15-120). In 58% (11/19) of the centers, imaging findings were reported to influence the clinical staging. MRI in combination with PET-CT was the preferred imaging method and the results influenced treatment planning. Robotic-assisted radical hysterectomy was the preferred surgical method in 72% (13/18) of the centers. Sentinel lymph node procedure was not routinely implemented in the majority of the Nordic centers. ConclusionMore than half of the Nordic Gynecological Oncology Centers already report a clinical FIGO stage influenced by pretreatment imaging findings. The trend in preferred treatment is robotic-assisted radical hysterectomy and the sentinel lymph node procedure is gradually being introduced.

n/a, Regrettably, the author metadata used for the previous correction (doi: https://doi.org/10.1007/s00428-018-2380-7) contained an error in the tagging of W. Glenn McCluggage’s name; this has been corrected. No further adjustments have been made to the Correction, or the original Guideline paper (doi: https://doi.org/10.1007/s00428-018-2362-9).

n/a, Correction to: Virchows Arch (2018) https://doi.org/10.1007/s00428-018-2362-9Two corrections were made to the above publication following its original online publication on 4th May 2018.

Purpose: The health-related quality of life (HRQoL) outcomes after comprehensive surgical staging including infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer (EC) are unknown. Our aim was to investigate the long-term HRQoL between robot-assisted laparoscopic surgery (RALS) and laparotomy (LT). Patients and Methods: A total of 120 women with high-risk stage I-II EC were randomised to RALS or LT for hysterectomy, bilateral salpingoophorectomy, pelvic and infrarenal paraaortic lymphadenectomy in the previously reported Robot-Assisted Surgery for High-Risk Endometrial Cancer trial. The HRQoL was measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-30) and its supplementary questionnaire module for endometrial cancer (QLQ-EN24) questionnaire. Women were assessed before and 12 months after surgery. In addition, the EuroQol Eq5D non-disease specific questionnaire was used for descriptive analysis. Results: There was no difference in the functional scales (including global health status) in the intention to treat analysis, though LT conferred a small clinically important difference (CID) over RALS in cognitive functioning albeit not statistically significant -6 (95% CI-14 to 0, p = .06). LT conferred a significantly better outcome for the nausea and vomiting item though it did not reach a CID, 4 (95% CI 1 to 7, p = .01). In the EORTC-QLQ/QLQ-EN24, no significant differences were observed. Eq5D-3L questionnaire demonstrated a higher proportion of women reporting any extent of mobility impairment 12 months after surgery in the LT arm (p = .03). Conclusion: Overall, laparotomy and robot-assisted surgery conferred similar HRQoL 12 months after comprehensive staging for high-risk EC., Funding Agencies|Radiumhemmets Forskningsfonder

Background: Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer. Objective: The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide. Methods: The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives. Results: The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined. (C) 2018 European Society for Gynaecological Oncology, European Society for Radiotherapy and Oncology, and th, Funding Agencies|Institut National du Cancer (France)

Objective The aim of this survey was to acquire an overview of the current management of cervical cancer with an emphasis on the early disease stages. Materials and Methods A hyperlink to the survey was sent to the European Society of Gynaecological Oncology Office database. The survey contained 6 groups of questions regarding the characteristics of respondents, pretreatment workup, management of the early stages of cervical cancer, adjuvant treatment, fertility-sparing treatment, and surveillance. Results In total, 566 responses were collected. The most frequent imaging method used in the workup was magnetic resonance imaging (74%), followed by computed tomography (54%) and positron emission tomography/computed tomography (25%). Conization or simple hysterectomy was a preferred procedure in stage T1a1 lymphovascular space invasion (LVSI)-positive for 79% of respondents, in stage T1a2 LVSI-negative for 58%, and in stage T1a2 LVSI-positive for 28%. Sentinel lymph node biopsy alone was reported in stage T1a1 by 17% and in stage T1b1 less than 2 cm by 9%, whereas systematic lymphadenectomy by 29% and 90% of respondents. Macrometastases, micrometastases, and isolated tumor cells in lymph nodes were considered indications for adjuvant treatment by 96%, 93%, and 68% of respondents, respectively. Neoadjuvant chemotherapy was reported by 28% and 19% of respondents in fertility-sparing and nonsparing management in stage T1b1. Over 60% of respondents recommend primary surgery for their patients with T1b2 N0 disease and 81% of them use a combination of adverse prognostic factors as indication for adjuvant radiotherapy in pN0 disease. Conclusions The results of this survey indicate considerable differences in the workup and treatment of cervical cancer in current clinical practice., Funding Agencies|Charles University in Prague [UNCE 204065, Q28/LF1]

Gynecologic Cancer Intergroup Symptom Benefit Study (GCIG-SBS) Stage 2 aimed to review, revise, and validate a patient-reported outcome measure (PROM), the Measure of Ovarian Symptoms and Treatment concerns (MOST), developed in GCIG-SBS Stage 1 (MOSTv1, 35 items), and document recurrent ovarian cancer (ROC) symptom burden and benefit. GCIG-SBS Stage 2 recruited patients with platinum-resistant/refractory ROC (PRR-ROC) or potentially platinum-sensitive ROC with aeamp;lt;yenamp;gt; 3 lines of prior chemotherapy (PPS-ROC aeamp;lt;yenamp;gt; 3). Patients completed MOSTv1, QLQ-C30, QLQ-OV28, and FACT-O/FOSI at baseline and before cycle 3 of chemotherapy (pre-C3), and global assessments of change (MOST-Change) pre-C3. Clinicians rated patients cancer-related symptoms, performance status, and adverse events. Convergent and divergent validity (Spearmans correlations), discriminative validity (effect sizes between groups classified by clinician-rated characteristics), and responsiveness (paired t tests in patients expected to experience clinically meaningful change) were assessed. Of 948 recruits, 903 completed PROMs at baseline and 685 pre-C3. Baseline symptom burden was substantial for PRR-ROC and PPS-ROC aeamp;lt;yenamp;gt; 3. MOSTv2 has 24 items and five multi-item scales: abdominal symptoms (MOST-Abdo), disease or treatment-related symptoms (MOST-DorT), chemotherapy-related symptoms (MOST-Chemo), psychological symptoms (MOST-Psych), and MOST-Well-being. Correlations confirmed concurrent and divergent validity. Discriminative validity was confirmed by effect sizes that conformed with a priori hypotheses. MOST-Abdo was responsive to improvements in abdominal symptoms and MOST-Chemo detected the adverse effects of chemotherapy. The MOSTv2 validly quantifies patient-reported symptom burden, adverse effects, and symptom benefit in ROC, and as such is fit-for-purpose for clinical trials of palliative chemotherapy in ROC. Further research is required to assess test-retest reli, Funding Agencies|NHMRC [1063012, 570,893]; Target Ovarian Cancer [UCL-P001AL]; Cancer Research UK [C444/A15953]; UCL Cancer Trials Centre [C444/A15953]; Australian Government through Cancer Australia; NHMRC; Department of Health

PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes. EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/ gene-based analyses were used to compare variant frequencies among neuropathy groups and Cox regression models were used to analyze neuropathy evolution along treatment. RESULTS: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low frequency non-synonymous variants in EPHA6 were present exclusively in patients with high neuropathy and all affected the ligand binding domain. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency non-synonymous variant carriers (HR=14.60, 95%CI=2.33-91.62, P=0.0042) and an independent cohort confirmed an increased neuropathy risk (HR=2.07, 95%CI=1.14-3.77, P=0.017). Combining the series gave an estimated 2.50-fold higher risk of neuropathy (95%CI=1.46-4.31; P=9.1x10(-4)). CONCLUSION: This first study sequencing EPHA genes revealed that low frequency variants in EPHA6, EPHA5 and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHAs neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs., Funding agencies: Spanish Ministry of Economy and Competiveness [SAF2015-64850-R]; Severo Ochoa Excellence Programme [SEV-2011-0191]; Fundacion AECC; Swedish Cancer Society; Swedish Research Council; LiU Cancer