| 1. |
- Concin, Nicole, et al.
(författare)
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European Society of Gynaecological Oncology quality indicators for the surgical treatment of endometrial carcinoma
- 2021
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Ingår i: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. - : BMJ. - 1048-891X. ; 31:12, s. 1508-1529
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Quality of surgical care as a crucial component of a comprehensive multi-disciplinary management improves outcomes in patients with endometrial carcinoma, notably helping to avoid suboptimal surgical treatment. Quality indicators (QIs) enable healthcare professionals to measure their clinical management with regard to ideal standards of care. OBJECTIVE: In order to complete its set of QIs for the surgical management of gynecological cancers, the European Society of Gynaecological Oncology (ESGO) initiated the development of QIs for the surgical treatment of endometrial carcinoma. METHODS: QIs were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for the identification of potential QIs and documentation of the scientific evidence, two consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians and patient representatives. QIs were defined using a structured format comprising metrics specifications, and targets. A scoring system was then developed to ensure applicability and feasibility of a future ESGO accreditation process based on these QIs for endometrial carcinoma surgery and support any institutional or governmental quality assurance programs. RESULTS: Twenty-nine structural, process and outcome indicators were defined. QIs 1-5 are general indicators related to center case load, training, experience of the surgeon, structured multi-disciplinarity of the team and active participation in clinical research. QIs 6 and 7 are related to the adequate pre-operative investigations. QIs 8-22 are related to peri-operative standards of care. QI 23 is related to molecular markers for endometrial carcinoma diagnosis and as determinants for treatment decisions. QI 24 addresses the compliance of management of patients after primary surgical treatment with the standards of care. QIs 25-29 highlight the need for a systematic assessment of surgical morbidity and oncologic outcome as well as standardized and comprehensive documentation of surgical and pathological elements. Each QI was associated with a score. An assessment form including a scoring system was built as basis for ESGO accreditation of centers for endometrial cancer surgery.
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| 2. |
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| 3. |
- Froyman, Wouter, et al.
(författare)
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Risk of complications in patients with conservatively managed ovarian tumours (IOTA5) : a 2-year interim analysis of a multicentre, prospective, cohort study
- 2019
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 20:3, s. 448-458
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. Methods: In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. Findings: Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in follow-up at recruitment, and 1919 (74%) presented with a new mass at recruitment (ie, not already in follow-up in the centre before recruitment). Median follow-up of patients with new masses was 27 months (IQR 14–38). The cumulative incidence of spontaneous resolution within 2 years of follow-up among those with a new mass at recruitment (n=1919) was 20·2% (95% CI 18·4–22·1), and of finding invasive malignancy at surgery was 0·4% (95% CI 0·1–0·6), 0·3% (<0·1–0·5) for a borderline tumour, 0·4% (0·1–0·7) for torsion, and 0·2% (<0·1–0·4) for cyst rupture. Interpretation: Our results suggest that the risk of malignancy and acute complications is low if adnexal masses with benign ultrasound morphology are managed conservatively, which could be of value when counselling patients, and supports conservative management of adnexal masses classified as benign by use of ultrasound. Funding: Research Foundation Flanders, KU Leuven, Swedish Research Council.
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| 4. |
- Garcia-Dios, Diego A, et al.
(författare)
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High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma.
- 2013
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 128:2, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Endometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies. METHODS: Primary endometrial tumors were genotyped for >100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n=1063). RESULTS: PIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR=2.03; P=0.001 for grade 2 and OR=1.89; P=0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR=11.92; P<0.001) and PTEN mutations with type I tumors (OR=19.58; P=0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR=3.38; P=0.045). When assessing the effects of individual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR=2.18; P=0.028). CONCLUSIONS: Mutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients.
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| 5. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 6. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 7. |
- Oonk, Maaike H. M., et al.
(författare)
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Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node : Results of GROINSS-V II
- 2021
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Ingår i: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 39:32, s. 3623-3632
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (<= 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.
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| 8. |
- Serreyn Lundin, Evelyn, 1969-
(författare)
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On Quality Improvement in Gynaecological Cancer Surgery
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: The overall purpose of this thesis was to find medical and surgical treatment methods of improving the perioperative care of gynaecological cancer patients. The specific objectives were to determine whether a single dose tranexamic acid given immediately before surgery for presumed advanced ovarian cancer reduces perioperative blood loss and the need for blood transfusions, and to determine whether postoperative recovery, tissue damage, and inflammatory response markers differ between women operated with robotic and abdominal hysterectomy for low-risk endometrial cancer in an enhanced recovery after surgery (ERAS) programme, and to evaluate costs for hospital stay and postoperative recovery in relation to health impact. Material and Methods: The thesis was based on two randomised trials. The first trial was a randomised double-blind placebo-controlled multicentre study conducted in four hospitals in the southeast and central of Sweden between March 2008 and May 2012. One hundred women with presumed advanced ovarian cancer who had been scheduled for radical debulking surgery were included; 50 received tranexamic acid and 50 received a placebo. The main outcomes were blood loss and red blood cell transfusions. The second trial was a randomised open single centre trial at a Swedish university hospital, which included 50 women with low-risk endometrial cancer scheduled for radical surgery between February 2012 and May 2016; 25 women underwent robotic hysterectomy and 25 had abdominal hysterectomy. Anaesthesia and perioperative care followed an ERAS protocol in both groups. The EuroQol Group form EQ-5D-3L and the Short Form-36 evaluated the health-related quality of life. The Swedish Postoperative Symptoms Questionnaire assessed symptoms perioperatively until six weeks postoperatively. Venous blood samples were collected on several occasions until six weeks postoperatively and were analysed for markers reflecting inflammatory response and tissue damage. In addition, a health economic evaluation was conducted comparing total costs, qualityadjusted life years (QALYs) and cost per QALY between the surgical methods. Results: Total blood loss volume and transfusion rate following surgery in advanced ovarian cancer were significantly lower in the tranexamic group compared with the placebo group. Women with early endometrial cancer treated by robotic hysterectomy recovered significantly faster in the EQ-5D health index, and reached their preoperative level nearly two weeks earlier than the abdominal group. Differences regarding improvement in health-related quality of life (Short Form-36) comprising general health and social functioning were more favourable in the robotic hysterectomy group. Consumption of analgesics, pain intensity, postoperative symptom sum score and length of hospital stay were equal between the groups. The occurrence of complications was an independent risk factor and influenced most of the outcome measures adversely. Postoperative inflammatory response and tissue damage were lower after robotic hysterectomy compared with the abdominal approach. The robotic group gained more QALYs until six weeks after surgery than the abdominal group but the total costs were higher. The total cost per QALY gained was quite high for the robotic procedure. Conclusions: A single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates in advanced ovarian cancer surgery. Robotic hysterectomy in an ERAS programme treating early endometrial cancer leads to a faster recovery in the health-related quality of life than abdominal hysterectomy, the latter being strongly influenced by perioperative complications. Less tissue damage and inflammation might contribute to a faster recovery in the robotic group. Robotic hysterectomy provides more QALYs until six weeks postoperatively but with a substantially higher total cost for the society.
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| 9. |
- Van Calster, Ben, et al.
(författare)
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Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively : multicentre cohort study
- 2020
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 370
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.
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| 10. |
- Björn, Niclas, et al.
(författare)
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ABCB1 Variation Affects Myelosuppression, Progression-free Survival and Overall Survival in Paclitaxel/Carboplatin-treated Ovarian Cancer Patients
- 2018
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : WILEY. - 1742-7835 .- 1742-7843. ; 123:3, s. 277-287
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Tidskriftsartikel (refereegranskat)abstract
- The standard chemotherapy for ovarian cancer is paclitaxel/carboplatin. Patients often exhibit myelosuppressive toxicity, and the treatment response varies considerably. In this study, we investigated the previously reported SNPs 1199Gamp;gt;A (rs2229109), 1236Camp;gt;T (rs1128503), 2677Gamp;gt;T/A (rs2032582), 3435Camp;gt;T (rs1045642) in ABCB1, and 1196Aamp;gt;G (rs10509681) in CYP2C8 and their association with treatment-induced myelosuppression, progression-free survival (PFS) and overall survival (OS). From the phase III study, OAS-07OVA, 525 patients (All) treated with carboplatin and paclitaxel administered as Paclical (Arm A, n=260) or Taxol((R)) (Arm B, n=265) were included and genotyped using pyrosequencing. Genotype associations with myelosuppression, PFS and OS were investigated using anova, Kaplan-Meier analysis and Cox proportional hazard models. The most prominent finding was for the ABCB1 variant 3435TT, which was significantly associated with increased PFS in All (hazard ratio (HR) = 0.623), in Arm A (HR=0.590) and in Arm B (HR=0.627), as well as increased OS in All (HR=0.443) and in Arm A (HR=0.372) compared to the wild-type, 3435CC. For toxicity, the most interesting finding concerned the haplotype, including 1236TT, 2677TT and 3435TT, which was associated with higher neutrophil values in Arm B (p=0.039) and less neutrophil decrease in All (p=0.048) and in Arm B (p=0.021). It is noteworthy that the results varied depending on the treatment arm which indicates that the effects of ABCB1 variants vary with the treatment regimen. Our results reflect the contradictory results of previous studies, confirming that small variations in the composition of treatment regimens and patient populations may influence the interpretation of SNPs effects on treatment outcome.
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