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BACKGROUND: Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy. METHODS: We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin mono- therapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator's choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or peme- trexed). The primary end point was overall survival. RESULTS: A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30°6 lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P=0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 1Z8°6 in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; twosided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2°6 in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.396, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects. CONCLUSIONS: In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Circumferential measurements (CMs) every 4th cm are commonly used to assess lower limb volume (LLV), but fewer measurements would be less time-consuming. The aim of this study was therefore to establish the agreement between LLV measurements derived from CM every 4th cm (V4), 8th cm (V8), and 12th cm (V12), and to evaluate the intrarater test-retest reliability for each of the three measurement methods in persons with lower limb lymphedema (LLL). Methods and Results: Forty-two persons with unilateral or bilateral LLL were measured twice, 2 weeks apart. Volume measurements for the V4, V8, and V12 methods were derived using CM. The agreement was evaluated using intraclass correlation coefficient (ICC 3.1 ) and Bland-Altman graphs including 95% limits of agreement (LOA). The reliability was evaluated using ICC 2.1 and standard error of measurement (SEM%) and smallest real difference (SRD%). The agreement was high for the V4 and V8 methods (ICC 0.999), and for the V4 and V12 methods (ICC 0.998). The graphs revealed slightly higher agreement between the V4 and V8 than between the V4 and V12 methods visualized by the 95% LOA (-117 to 62 and -236 to 132 mL, respectively). For all three measurement methods, the test-retest reliability was high (ICC 0.993-0.995) and the measurement error low (SEM%: 1.2%-1.4% and SRD%: 3.4%-3.8%). Conclusions: The higher agreement between the V4 and V8 methods than between V4 and V12, and the high test-retest reliability in LLV measurements support the V8 method to replace the V4 method in persons with LLL.

Background: Imaging ovarian cancer (OC) includes evaluating peritoneal carcinomatosis (PC) and enlarged cardio phrenic lymph nodes (CPLN) by computed tomography (CT), and thorough evaluation is tedious work. A "CT short score" with high-risk CT parameters might be a more pragmatic approach, but it is not known if such a short score associates with aggressive OC subtypes and impaired OC survival. Further, it is not known if certain established OC risk factors are linked to high-risk CT-findings which would be important in image evaluation. Herein, we investigate a CT short score and its relation to baseline characteristics, OC subtypes, and survival., Methods: The Malmö Diet and Cancer Study is a prospective cohort that included 17,035 women (1991-1996). Baseline characteristics and tumor information on 159 OC and information on OC specific survival (last follow-up, 2017-12-31) was registered. A CT short score (CPLN and PC-index (PCI) in seven regions) was registered and associations with clinical stage [stage I vs. advanced stage (II-IV), histological type/grade (high grade serous and endometrioid vs. other subtypes], and OC-specific survival were analyzed with logistic and Cox regression, respectively. Parity and menopausal status were analyzed in relation to short score and PCI., Results: There was an association between higher short score and advanced clinical stage (adjusted OR 2.76 (1.42-5.38)), adjusted for age at diagnosis and histological type/grade. Higher short score was associated with impaired OC specific survival (adjusted HR 1.17 (1.01-1.35)), adjusted for age at diagnosis, histological type/grade, and clinical stage. There were no significant associations between parity, menopausal status, and short score/PCI., Conclusions: CT short score was significantly associated with advanced clinical stages and impaired OC survival. A pragmatic approach (based on CT) to evaluate high risk image findings in OC could help reduce radiologists' workload and at the same time provide structured reports to surgeons and oncologists involved in OC care., (© 2023. The Author(s).)

Background: Cervical cancer is the fourth most common female malignancy. [ 18 F]-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) is routinely performed in patients with locally advanced cervical cancer for staging and treatment response evaluation. With this retrospective, observational cohort study, we wanted to investigate the prognostic value of the maximum standardised uptake value (SUVmax) and the volumetric parameters of metabolic tumour volume (MTV) and total lesion glycolysis (TLG) before and after treatment in women with cervical cancer, with overall survival (OS) and recurrence as outcome measures., Methods: Women with cervical cancer referred for curative radiotherapy and who underwent two PET-CT scans (before treatment and approximately 7 months post-treatment) were included. SUVmax, MTV and TLG were measured at baseline and post-treatment on the primary tumour, pelvic and distant lymph node metastases, distant organ metastases, and on total tumour burden. The PET parameters were associated with OS by Cox regression and recurrence by multivariable logistic regression. Kaplan-Meier curves and C-index were used to visualise the prognostic potential of the different measures., Results: A total of 133 patients were included. At the primary tumour level and on total tumour burden, age- and clinical-stage adjusted analyses showed a significant association between PET parameters and OS and recurrence when measured post-treatment. At baseline (pre-treatment), MTV and TLG were associated with OS and recurrence, whereas SUVmax was not. C-index from adjusted Cox models on total tumour burden showed higher values for the post-treatment PET compared to baseline. Kaplan-Meier curves demonstrated a greater prognostic potential for MTV and TLG compared to SUVmax, both at baseline and post-treatment., Conclusions: The FDG PET-CT-derived parameters SUVmax, MTV, and TLG measured post-treatment can predict OS and recurrence in cervical cancer. Parameters measured before treatment had overall lower prognostic potential, and only MTV and TLG showed significant association to OS and recurrence.

Purpose: The aim of this randomized controlled trial was to evaluate the potential benefit from 2 probiotic bacteria of the species Lactiplantibacillus plantarum against radiation therapy-induced comorbidities., Methods and Materials: Women (>18 years of age) scheduled for radiation therapy because of gynecologic cancer were randomly allocated to consume placebo or either low-dose probiotics (1 × 10 10 colony-forming unit/capsule twice daily) or high-dose probiotics (5 × 10 10 colony-forming unit/capsule twice daily). The intervention started approximately 1 week before the onset of radiation therapy and continued until 2 weeks after completion. During this period the participants were daily filling in a study diary documenting the incidence and severity of symptoms, intake of concomitant medication, and stool consistency. The primary endpoint was the probiotic effect on the mean number of loose stools during radiation therapy., Results: Of the 97 randomized women, 75 provided data for the analysis of the results. The mean number of loose stools (sum of Bristol stool type 6 and 7) was not significantly reduced in the probiotic groups, but there was a significant reduction in the mean number of days with >1 loose stool with 15.04 ± 8.92 days in the placebo and 8.65 ± 5.93 days in the high-dose probiotics group ( P  = .014). The benefit was even more pronounced in the 2 weeks following the end of radiation therapy ( P  = .005). Moreover, intake of the probiotics resulted in a reduced severity of the symptoms grinding abdominal pain ( P  = .041) and defecation urgency ( P  = .08) and a reduced percentage of days with these symptoms ( P  = .023 and P  = .042, respectively), compared with placebo. There were no differences regarding reported adverse events., Conclusions: Intake of the 2 probiotic bacteria was beneficial and reduced many measures or symptoms of the radiation-induced toxicity in women treated for gynecologic cancer., (© 2022 The Authors.)

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, respectively., Conclusions: There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Lower limb lymphedema (LLL) is a chronic condition. To be able to evaluate changes of LLL over time and effects of interventions, reliable measurement methods are important. Currently, there is limited knowledge of the reliability of commonly used measurement methods in LLL. The study objective was to evaluate the test-retest (intrarater) reliability of impedance of extracellular fluid, volume, and local tissue water measurements in people with unilateral or bilateral LLL and measurement errors both for a group of people and for a single individual., Methods: Forty-two people with mild to moderate unilateral or bilateral, primary or secondary LLL were measured twice, 2 weeks apart. Impedance of extracellular fluid was measured by bioimpedance spectroscopy and calculated as arm-to-leg ratio, volume with circumference measurements every 4 cm, and local tissue water with tissue dielectric constant at 14 points. Test-retest reliability was evaluated using the intraclass correlation coefficient [ICC(2,1)], changes in the mean, SE of measurement in relative terms (SEM%), and the smallest real difference in relative terms (SRD%)., Results: For the impedance ratio, the reliability was high [ICC(2,1) = 0.79-0.90] and the measurement errors were acceptable (SEM% = 5.0%-5.2%; SRD% = 14.0%-14.4%). For volume, the reliability was high (ICC = 0.99) and the measurement errors were low (SEM% = 1.1%-1.7%; SRD% = 3.1%-4.6%). For the tissue dielectric constant, the reliability was fair to excellent [ICC(2,1) = 0.68-0.96] and the measurement errors were acceptable (SEM% = 4.2%-9.7%; SRD% = 11.7%-26.8%)., Conclusions: Measurements of impedance of extracellular fluid, volume, and local tissue water are reliable in people with mild to moderate LLL. The measurement errors were acceptable in all 3 methods indicating that real, clinical changes in lymphedema can be measured both for a group of people and a single individual., Impact: The results from this test-retest reliability study can help clinicians and researchers to interpret if real clinical changes in lymphedema occur over time or after an intervention in people with mild to moderate LLL., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

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.HighlightsSurgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival.A prolonged wait time to surgery did not worsen prognosis.Delay in time to surgery was associated with sociodemographic factors.

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., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

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,1.19-1.47, p < 0.001) for NACT+IDS and 3.00 (95%CI,2.66-3.38, 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., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

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 adhered to guidelines. Areas of improvement include treatment for stage II and for the very old., Competing Interests: Declaration of Competing Interest Dr. Avall-Lundqvist: Honoraria: Roche; Advisory board: Astra Zeneca, Clovis Oncology, Tesaro and Genmab. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: It is time-consuming for oncologists to delineate volumes for radiotherapy treatment in computer tomography (CT) images. Automatic delineation based on image processing exists, but with varied accuracy and moderate time savings. Using convolutional neural network (CNN), delineations of volumes are faster and more accurate. We have used CTs with the annotated structure sets to train and evaluate a CNN., Material and Methods: The CNN is a standard segmentation network modified to minimize memory usage. We used CTs and structure sets from 75 cervical cancers and 191 anorectal cancers receiving radiation therapy at Skåne University Hospital 2014-2018. Five structures were investigated: left/right femoral heads, bladder, bowel bag, and clinical target volume of lymph nodes (CTVNs). Dice score and mean surface distance (MSD) (mm) evaluated accuracy, and one oncologist qualitatively evaluated auto-segmentations., Results: Median Dice/MSD scores for anorectal cancer: 0.91-0.92/1.93-1.86 femoral heads, 0.94/2.07 bladder, and 0.83/6.80 bowel bag. Median Dice scores for cervical cancer were 0.93-0.94/1.42-1.49 femoral heads, 0.84/3.51 bladder, 0.88/5.80 bowel bag, and 0.82/3.89 CTVNs. With qualitative evaluation, performance on femoral heads and bladder auto-segmentations was mostly excellent, but CTVN auto-segmentations were not acceptable to a larger extent., Discussion: It is possible to train a CNN with high overlap using structure sets as ground truth. Manually delineated pelvic volumes from structure sets do not always strictly follow volume boundaries and are sometimes inaccurately defined, which leads to similar inaccuracies in the CNN output. More data that is consistently annotated is needed to achieve higher CNN accuracy and to enable future clinical implementation., Competing Interests: OE and JU are board members and stockholders of Eigenvision AB, which is a company working with research and development in automated image analysis, computer vision and machine learning. The other authors declare that they have no conflict of interest., (© 2020 The Author(s).)

Background: Measurements of lower limb (LL) volume and local tissue water by tissue dielectric constant (TDC) are common in lymphedema management. Knowledge of normal variability in health subjects is important and can serve as a base for early lymphedema diagnosis but is currently lacking. The aim of this study was to evaluate test-retest reliability of LL volume and TDC values in healthy women and men. Methods and Results: Thirty-three women and 28 men were measured twice, 2 weeks apart. Volume was calculated from circumferential measurements every 4 cm and TDC in 14 points. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC), changes in the mean, standard error of measurement in percentage (SEM%), and smallest real difference in percentage (SRD%). For volume, reliability was high (ICC 0.99) and measurement errors were low in both women and men (SEM%: 1.1%-1.3%; SRD%: 3.1%-3.6%). For TDC, reliability was fair to excellent in women (ICC 0.63-0.93) and poor to excellent in men (ICC 0.21-0.89). Measurement errors were acceptable in all points in women (SEM%: 3.9%-10.2%; SRD% 10.8%-28.2%), but only in 11 points in men (SEM%: 3.9%-14.5%; SRD%: 10.9%-40.1%). The points close to bone and tendons in men had lower reliability and higher measurement errors. Conclusion: Measurements of LL volume and TDC are reliable in healthy women and men; both methods can be recommended. However, TDC points close to bone and tendons in men should be used with caution.

Background: Ovarian cancer (OC) is usually detected in late clinical stages, and imaging at diagnosis is crucial. Peritoneal carcinomatosis (PC) and cardio phrenic lymph nodes (CPLN) are pathological findings of computed tomography (CT) and are relevant for surgical planning. Furthermore, mammographic breast density (BD) has shown an association with OC risk and might be prognostically relevant. However, it is not known if PC, CPLN, and BD are associated with aggressive OC subtypes and impaired OC survival. Herein, we investigated associations between three comprehensive image parameters and OC subtypes and survival., Methods: The Malmö Diet and Cancer Study is a prospective study that included 17,035 women (1991-1996). Tumor information on 159 OC and information on OC specific survival (last follow-up, 2017-12-31) was registered. The CT and mammography closest to diagnosis were evaluated (Peritoneal Carcinomatosis Index PCI, CPLN, and BD). Associations between CT-PCI, CPLN, and BD vs. clinical stage [stage I vs. advanced stage (II-IV), histological type/grade (high grade serous and endometrioid vs. other subtypes], and OC-specific survival were analyzed by logistic and Cox regression., Results: There was a significant association between higher CT-PCI score and advanced clinical stage (adjusted OR 1.26 (1.07-1.49)), adjusted for age at diagnosis and histological type/grade. Increasing CT-PCI was significantly associated with impaired OC specific survival (adjusted HR 1.04 (1.01-1.07)), adjusted for age at diagnosis, histological type/grade, and clinical stage. There was no significant association between PCI and histological type/grade, nor between BD or CPLN vs. the studied outcomes., Conclusions: Image PCI score was significantly associated with advanced clinical stages and impaired OC survival. An objective approach (based on imaging) to scoring peritoneal carcinomatosis in ovarian cancer could help surgeons and oncologists to optimize surgical planning, treatment, and care.

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 CT-RT, 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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.

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.

Objective: Aim of this study was observation of hypersensitivity reaction (HSR) frequency by using a 3-hour graduated infusion protocol with appropriate premedication as a prophylactic measure in patients with gynecological cancer receiving carboplatin retreatment in second line or above. None of the patients had experienced HSRs to platinum previously., Method: All the patients in this study received premedication with corticosteroids and anti-histamines followed by carboplatin as 3-hour graduated infusion. Carboplatin was administered either as monotherapy or in combination with other chemotherapeutic agents., Results: Ninety-nine patients with ovarian (n=71), fallopian tube (n=9), peritoneal (n=9) and other gynecological cancers (5 uterine cancer, 5 abdominal cancer of gynecological origin) were retreated by a total of 611cycles of carboplatin administered as monotherapy (210cycles) or combination regime (401cycles). HSRs were recorded in only 11cycles (1.8%) in a total of 11 patients. While 8 of these patients had grade 1or 2 reactions (8.1%), only 3 patients had grade 3 reactions (3%). After pause in the infusion and complete resolution of HSR symptoms, an attempt of retreatment using this infusion protocol with extra premedication was successful in 6 of these patients without any reoccurrence of HSRs., Conclusion: In this prospective study, we report that prophylactic 3-hour graduated infusion rate with appropriate premedication is associated with low frequency of HSRs in gynecological cancer patients requiring carboplatin retreatment in second line or above., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin., Methods: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models., Results: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy., Conclusion: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The AGO-OVAR 2.29/ENGOT-ov14/PENELOPE prospectively randomized phase III trial evaluated the addition of pertuzumab to chemotherapy in patients with platinum-resistant ovarian carcinoma with low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression. We report the results of the primary efficacy analysis., Patients and Methods: Eligible patients had ovarian carcinoma that progressed during or within 6 months of completing four or more platinum cycles, centrally tested low tumor HER3 mRNA expression (concentration ratio ≤ 2.81 by quantitative reverse transcriptase polymerase chain reaction on cobas z480 [Roche Molecular Diagnostics, Pleasanton, CA]), and no more than two prior lines of chemotherapy. After investigators' selection of the chemotherapy backbone (single-agent topotecan, weekly paclitaxel, or gemcitabine), patients were randomly assigned to also receive either placebo or pertuzumab (840-mg loading dose followed by 420 mg every 3 weeks). Stratification factors were selected chemotherapy, prior antiangiogenic therapy, and platinum-free interval. The primary end point was independent review committee-assessed progression-free survival (PFS). Additional end points included overall survival, investigator-assessed PFS, objective response rate, safety, patient-reported outcomes, and translational research., Results: Overall, 156 patients were randomly assigned. Adding pertuzumab to chemotherapy did not significantly improve independent review committee-assessed PFS for the primary analysis (stratified hazard ratio, 0.74; 95% CI, 0.50 to 1.11; P = .14; median PFS, 4.3 months for pertuzumab plus chemotherapy v 2.6 months for placebo plus chemotherapy). Sensitivity analyses and secondary efficacy end point results were consistent with the primary analysis. The effect on PFS favoring pertuzumab was more pronounced in the gemcitabine and paclitaxel cohorts. No new safety signals were seen., Conclusion: Although the primary objective was not met, subgroup analyses showed trends in PFS favoring pertuzumab in the gemcitabine and paclitaxel cohorts, meriting further exploration of pertuzumab in ovarian cancer., (© 2016 by American Society of Clinical Oncology.)

Cervical cancer is the third most common female cancer world wide. In Sweden, some 450 cases are diagnosed annually. One out of three affected Swedish women is under the age of 40. Survival for all stages is 73 % in Sweden. Human papilloma virus (HPV) can be detected in the majority of all cervical cancers. Treatment consists of surgery for early stages, and a combination of chemoradiation and brachytherapy for locally advanced disease. For metastatic disease, the treatment is palliative. Late side effects after treatment may have serious impact on the quality of life. There is a strong need for more efficient treatment of metastatic disease. Current lines of research include surgical strategies, optimised radiotherapy, neoadjuvant therapy, targeted therapy, and immunotherapy including therapeutic vaccines.

Introduction: In early-stage endometrial carcinoma, there is controversy regarding the prognostic value of the flow cytometric variables DNA ploidy (diploid vs. aneuploid) and S-phase fraction. In Sweden, the former is included in national guidelines despite poor scientific support and the latter is not used clinically. This study investigates the prognostic properties of these variables, together with classical histopathological variables, in multivariate analysis in a stringently stratified material., Material and Methods: Consecutive, population-based patient material restricted to International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I endometrioid endometrial carcinoma (n = 1140) was retrospectively collected from routinely reported data from medical records. Data on age, FIGO stage, degree of differentiation, S-phase fraction, DNA ploidy status, and adjuvant treatment were included in the study. Cumulative incidence curves with other causes of death as a competing risk were used for univariable analysis for the primary endpoint endometrial cancer death. Cox proportional hazards regression analysis was used for multivariate modeling of all endpoints, and for univariable analysis for the secondary endpoints overall survival and time to progression., Results: An S-phase fraction value of >5.5% was associated with worse outcome (for endometrial cancer death: hazard ratio 2.25; 95% CI 1.38-3.67; p = 0.001, adjusted) and DNA ploidy status was not, for all endpoints tested., Conclusions: In FIGO stage I endometrioid endometrial carcinoma, DNA ploidy status had no prognostic value, whereas the S-phase fraction may be used to identify those with a higher risk of adverse clinical outcome., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

The purpose of this study was to establish an experimental setting and an anesthetic method compatible with future sequential studies using (18)F-FDG-PET single scans, i.e. autoradiographic measurements, for the estimation of metabolic rate of glucose (MRglc) in mice. In this study we had no access to a small animal PET scanner and therefore focus was on the anesthetic setting and optimization of the input function as a preparation for the future tumor metabolic studies. Initially, four combinations of intraperitoneal (ip) anesthesia were tested on tumor bearing mice. Fentanyl-fluanisone plus diazepam yielded low and stable blood glucose levels and kept the animals sedated for approximately 2 h. The anesthesia was also tested in a longitudinal (18)F-FDG study, where tumor bearing mice were anesthetized, injected with (18)F-FDG, and sampled for blood, before, one day after, and 8 days after treatment with cisplatin. The animals were in good condition during the entire study period. To validate the method, average MRglc of whole brain and cerebellum in mice were calculated and compared with the literature. The average MRglc in the whole brain and cerebellum were 46.2±4.4 and 39.0±3.1 µmol 100g(-1) min(-1). In the present study, we have shown that an ip anesthesia with a combination of fentanyl-fluanisone and diazepam is feasible and provides stable and low blood glucose levels after a fasting period of 4 h in experiments in nude mice with xenografted human tumors. We have also verified that (18)F-FDG, intraperitoneally administrated, results in an expected plasma activity uptake and clearance. The method doesn't alter the uptake in brain which is an indirect indication that the anesthesia doesn't alter the uptake in other organs. In combination with meticulous animal handling this set-up is reliable and future sequential tumor studies of early metabolic effects with calculation of MRglc following cytotoxic therapy are made possible.

Objective: The superiority of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) over computed tomography and magnetic resonance imaging in detecting recurrent cervical cancer and determining the extent of the disease has been demonstrated in several clinical trials. However, there is a lack of data concerning the clinical impact of the extra findings. We report here a prospective clinical study aimed at investigating the clinical impact of FDG-PET findings on the treatment plans in recurrent cervical cancer., Materials and Methods: Thirty-six patients with suspected recurrent cervical cancer underwent FDG-PET. Relapses were confirmed in 26 cases, and one case of primary lung cancer was found. The clinical impact of the FDG-PET results was assessed using a systematic scoring system with a 4-grade scale. Median follow-up time after FDG-PET was 33.1 months (range, 5-83 months) for all patients and 22.4 months (range, 5-83 months) for patients with positive PET results., Results: More sites of metastases were detected with FDG-PET in 56% of the patients compared to the findings by conventional imaging. The results of FDG-PET led to a change in treatment modality for 33% of the patients; and for 22%, a change in dose or deliverance of treatment was recorded. Treatment intention was changed in 30%, in all but one patient, from curative to palliative. In 48% of the patients, the initially planned treatment was reduced regarding dose or extent, or was withheld., Conclusion: In recurrent cervical cancer, FDG-PET provides clinically valuable information with a high impact on treatment decisions.

PURPOSE: Early metabolic response with a decrease in glucose demand after cytotoxic treatment has been reported to precede tumor volume shrinkage. However, preclinical studies report of a very early rise in metabolism, a flare, following treatment. To elucidate these observations, we performed an experimental study on early metabolic response with sequential analysis of metabolic changes. METHODS: Three squamous cell carcinoma cell lines and one nontumorigenic cell line were exposed to cisplatin. The uptake of the fluorescent glucose analogue 2-NBDG was examined at days 1-6 using fluorescence microscopy. The relation between 2-NBDG-uptake and cell survival was evaluated. RESULTS: The tumor cells exhibited a high uptake of 2-NBDG, whereas the uptake in the nonmalignant cells was low. The more cisplatin sensitive cell lines exhibited a more pronounced metabolic flare than the less sensitive cell line. CONCLUSION: A metabolic flare was a very early sign of treatment response and potentially it could be used as an early marker of treatment sensitivity.

Introduction: It is difficult to assess the individual response of locally advanced cervical cancer to chemoradiation therapy during the course of treatment. We have investigated the predictive value of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) early during treatment in relation to progression-free survival., Methods: This prospective single-center clinical trial included women with locally advanced cervical cancer from 2004 to 2008. 2-Deoxy-2-[18F]fluoro-D-glucose-PET/computed tomography was performed at baseline, during the third week of treatment and, finally, 3 months after the completion of treatment. The images were evaluated visually, semiquantitatively with the maximum standardized uptake value, and by calculating the metabolic rate of FDG. Thirty-two patients were eligible for full evaluation., Results: The median follow-up time was 28 months (range, 5-53 months). Visual metabolic complete response on FDG-PET, after a mean irradiation dose of 23 Gy (range, 16-27 Gy), was found in 7 patients, none of which relapsed. Eleven of the 25 patients with remaining malignant hypermetabolism on the second FDG-PET relapsed. Neither maximum standardized uptake value nor metabolic rate of FDG could further discriminate between patients with low risk and patients with high risk of relapse. The follow-up FDG-PET performed 3 months after the completion of treatment identified a group of patients with poor prognosis., Conclusions: In conclusion, FDG-PET early during chemoradiation therapy identified a small number of patients with an excellent prognosis. However, FDG-PET at this early point in time during treatment failed to predict the outcome for most patients. Future clinical trials to determine the optimal timing of predictive FDG-PET are thus warranted.