G Lindahl

Impact of lymphadenectomy and lymphoedema on health‐related quality of life 1 year after surgery for endometrial cancer. A prospective longitudinal multicentre study

ObjectiveTo assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health‐related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC).DesignProspective longitudinal cohort multicentre study.SettingDepartments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden.PopulationTwo‐hundred‐and‐thirty‐five women with early stage EC were included; 116 with high‐risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low‐risk EC had surgery without lymphadenectomy (−LA).MethodsThe generic SF‐36 and EQ‐5D‐3L and the lymphoedema‐specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient‐reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4–6 weeks, 6 months and 1 year postoperatively.Main outcome measureHRQoL scores.ResultsNo significant differences were seen in HRQoL between the +LA and –LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL.ConclusionsLymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema‐specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL.Tweetable abstractLymphoedema has impact on lymphoedema‐specific, but not on generic, HRQoL, 1 year after surgery for EC.

Risk factors for lymph ascites after surgery for endometrial cancer and impact on lymphedema of the legs. A prospective longitudinal Swedish multicenter study

AbstractIntroductionThe primary aim was to determine the occurrence of lymph ascites 4–6 weeks after surgery for endometrial cancer. Secondary aims were to assess risk factors for lymph ascites and the association with lymphedema of the legs.Material and MethodsThis was a post hoc analysis of an observational prospective multicenter study, performed in 14 Swedish hospitals that included 235 women undergoing surgery for early‐stage endometrial cancer between June 2014 and January 2018; 116 underwent surgery including pelvic and para‐aortic lymphadenectomy and 119 had surgery without lymphadenectomy. Lymph ascites (free intraabdominal fluid or encapsulated pelvic or para‐aortic fluid) was assessed by vaginal ultrasound 4–6 weeks postoperatively. Lymphedema was assessed using circumferential measurements of the legs preoperatively and 1 year postoperatively, enabling estimation of leg volume. A BMI‐standardized leg volume increase ≥10% was classified as lymphedema. Evaluation of risk factors was performed using multiple logistic regression.ResultsLymph ascites 4‐6‐weeks postoperatively occurred in 28.5% (67/235) of the women. The estimated volume of the lymph ascites in these women was mean 28 mL (standard deviation 48 mL) and median 14 mL (interquartile range 2–36 mL). Lymphadenectomy was a risk factor for lymph ascites (aOR 9.97; 95% CI 4.53–21.97) whereas the use of minimally invasive surgery (aOR 0.50; 95% CI 0.25–0.99) reduced the risk. Twenty‐two of 231 women (9.5%) developed lymphedema of the legs 1 year after surgery. The presence of lymph ascites was predictive of lymphedema (aOR 3.90; 95% CI 1.52–9.96).ConclusionsLymph ascites was common 4–6 weeks after surgery but in a low and clinically insignificant volume. Lymphadenectomy was a strong risk factor for lymph ascites and the use of minimally invasive surgery seemed to reduce the risk. Detection of lymph ascites at early postoperative follow‐up may be a means of selecting patients at high risk of developing lymphedema after treatment with endometrial cancer for preventive measures against lymphedema progression.

Beyond HRD Status: Unraveling Genetic Variants Impacting PARP Inhibitor Sensitivity in Advanced Ovarian Cancer

Abstract The management of advanced epithelial ovarian cancer (AOC) has undergone significant advancements with the emergence of molecular diagnostics, particularly in predicting responses to PARP inhibitors (PARPi) based on homologous recombination deficiency (HRD) status. However, understanding sensitivity and resistance beyond HRD status remains elusive. This study aims to explore molecular factors that may elucidate why HRD status does not consistently predict PARPi sensitivity. Therefore, we conducted a post hoc translational analysis of formalin-fixed paraffin-embedded tumor samples from the ENGOT-ov24/NSGO-AVANOVA part 1 and 2 trial (NCT02354131), focusing on alterations pertaining radiologic response and progression-free survival (PFS). DNA sequencing was performed using the TruSight Oncology 500 HT gene panel, with variants classified according to recent guidelines. HRD status had been assessed by Myriad MyChoice CDx. We identified, among 92 patients in the ENGOT-ov24/NSGO-AVANOVA part 1 and 2 trial, 151 pathogenic or likely pathogenic variants across 81 samples. PARPi-sensitizing variants were found in two out of 10 HRD-negative samples from patients with clinical benefit (PFS ≥12 months), whereas three out of 10 HRD-positive samples from patients having no benefit (PFS ≤6 months) harbored variants associated with PARPi resistance. Additionally, analysis of BRCA1 variants revealed that truncating variants in exon 11 correlated with clinical benefit when niraparib was combined with bevacizumab. Conclusively, our findings highlight the complexity of PARPi response in AOC and underscore the importance of exploring somatic variants beyond HRD status. Further investigation into exon 11 variants of BRCA1 and the potential of combination treatment is warranted. Significance: The irregular response to PARPi in HRD-positive and -negative tumors highlights the need for identifying additional biomarkers. This study explores the mutational landscape beyond HRD status in AOC, ultimately advancing precision oncology in future clinical practice.

The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy – the TABANETOC trial: study protocol for a randomized clinical multicenter trial

Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis. Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT. Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured. Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants. Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.