Symptomatic Lymphocele After Robot-Assisted Pelvic Lymphadenectomy as Part of the Primary Surgical Treatment for Cervical and Endometrial Cancer: A Retrospective Cohort Study.

STUDY OBJECTIVES: Pelvic lymph node dissection (PLND) is part of the primary treatment for early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer. Pelvic lymphocele is a postoperative complication of PLND, and when symptomatic, lymphoceles necessitate treatment. The aim of this study was to investigate the incidence and risk factors of symptomatic lymphocele after robot-assisted laparoscopic PLND in cervical and endometrial cancer. DESIGN: Retrospective cohort study. SETTING: Single-center academic hospital. PATIENTS: Two hundred and fifty-eight patients with cervical cancer and 129 patients with endometrial cancer. INTERVENTIONS: Pelvic lymphadenectomy by robot-assisted laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: The authors retrospectively included all patients with early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer who underwent pelvic lymphadenectomy by robot-assisted laparoscopic surgery between 2008 and 2022. Medical records were reviewed for the occurrence of a symptomatic lymphocele. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for developing a symptomatic lymphocele. In total, 387 patients, 258 with cervical cancer and 129 with endometrial cancer, were included in the study. The overall incidence of symptomatic lymphoceles was 9.6% with a median follow-up of 47 months [interquartile range 23-61]. For the entire cohort, smoking was the only significant risk factor for symptomatic lymphoceles identified in univariate (OR 2.47, 95% CI 1.19-5.11) and multivariate analysis (OR 2.42, 95% CI 1.16-5.07). For cervical cancer, body mass index (BMI) (OR 1.09, 95% CI 1.00-1.17) and prior abdominal surgery (OR 2.75, 95% CI 1.22-6.17) were also identified as significant independent risk factors. For endometrial cancer, age was identified as a significant independent risk factor (OR 0.90, 95% CI 0.83-0.97). CONCLUSION: This single-center cohort study demonstrated an incidence of almost 10% of symptomatic lymphoceles after robot-assisted laparoscopic PLND for cervical cancer and endometrial cancer, with a higher risk observed among patients who smoke at the time of diagnosis. Furthermore, risk factors differ between the 2 populations, necessitating further studies to establish risk models.

Introducing a novice surgeon to an experienced robotic gynaecological oncology team: An observational cohort study on the impact of a structured curriculum on outcomes of cervical cancer surgery.

OBJECTIVE: To evaluate the effect on patient outcomes when introducing a novice robotic surgeon, trained in accordance with a structured learning curriculum, to an experienced robotic surgery team treating cervical cancer patients. METHODS: Patients with early-stage cervical cancer who were treated with primary robot-assisted surgery between 2007 and 2019 were retrospectively included. In addition to the 165 patients included in a former analysis, we included a further 61 consecutively treated patients and divided all 226 patients over three groups: early learning phase of 61 procedures without structured training (group 1), experienced phase of 104 procedures (group 2), and the 61 procedures during introduction of a novice with structured training (group 3). Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to assess the learning curve effect. Patient outcomes between the groups were compared. RESULTS: Based on RA-CUSUM analysis, no learning curve effect was observed for group 3. Regarding surgical outcomes, mean operation time in group 3 was significantly shorter than group 1 (p < 0.001) and similar to group 2 (p = 0.96). Proportions of intraoperative and postoperative adverse events in group 3 were not significantly different from the experienced group (group 2). Regarding oncological outcomes, the 5-year disease-free survival, disease-specific survival, and overall survival in group 3 were not significantly different from the experienced group. CONCLUSIONS: Introducing a novice robotic surgeon, who was trained in accordance with a structured learning curriculum, resulted in similar patient outcomes as by experienced surgeons suggesting novices can progress through a learning phase without compromising outcomes of cervical cancer patients.

Mainstream genetic testing for women with ovarian cancer provides a solid basis for patients to make a well-informed decision about genetic testing.

BACKGROUND: There is a growing need for genetic testing of women with epithelial ovarian cancer. Mainstream genetic testing provides an alternative care pathway in which non-genetic healthcare professionals offer pre-test counseling themselves. We aimed to explore the impact of mainstream genetic testing on patients' experiences, turnaround times and adherence of non-genetic healthcare professionals to the mainstream genetic testing protocol. METHODS: Patients receiving pre-test counseling at the gynecology departments between April 2018 and April 2020 were eligible to participate in our intervention group. Patients receiving pre-test counseling at the genetics department between January 2017 and April 2020 were eligible to participate in our control group. We evaluated patients' experiences with questionnaires, consisting of questions regarding knowledge, satisfaction and psychosocial outcomes. Patients in the intervention group were sent two questionnaires: one after pre-test counseling and one after receiving their DNA test result. Patients in our control group were sent one questionnaire after receiving their test result. In addition, we collected data regarding turnaround times and adherence of non-genetic healthcare professionals to the mainstream genetic testing protocol. RESULTS: Participation was 79% in our intervention group (105 out of 133 patients) and 60% in our control group (91 out of 152 patients). Knowledge regarding genetics, decisional conflict, depression, anxiety, and distress were comparable in the two groups. In the intervention group, the risk of breast cancer in patients carrying a pathogenic germline variant was discussed less often (49% versus 74% in control group, p ≤ 0.05), and the mean score of regret about the decision to have genetic testing was higher than in the control group (mean 12.9 in the intervention group versus 9.7 in the control group, p ≤ 0.05), although below the clinically relevant threshold of 25. A consent form for the DNA test and a checklist to assess family history were present for ≥ 95% of patients in the intervention group. CONCLUSION: Mainstream genetic testing is an acceptable approach to meet the increase in genetic testing among women with epithelial ovarian cancer.

The attributive value of comprehensive surgical staging in clinically early-stage epithelial ovarian carcinoma: A systematic review and meta-analysis.

BACKGROUND: Tumor positivity and upstaging rates from various surgical staging steps performed in clinically early-stage epithelial ovarian carcinoma (EOC) vary widely in literature. AIM: To quantify tumor positivity and upstaging rates for all staging surgery steps in EOC patients. Differences between subgroups based on their clinical and histological characteristics are explored. METHODS: A systematic search using synonyms of 'ovarian cancer', 'neoplasm staging', and 'neoplasm metastasis' was conducted in PubMed, Embase, and the Cochrane Library. Meta-analysis was performed on 23 included studies, comprising 5194 clinical stage I or II EOC patients who underwent comprehensive surgical staging. Studies were assessed using the Newcastle-Ottawa Scale risk-of-bias tool. Pooled proportions and 95% confidence intervals were calculated using an inverse variance weighted random-effects model. RESULTS: Overall upstaging rate of clinically early-stage EOC patients was 18.7% (95%CI: 14.1-23.4%). Serous histology or high grade EOC showed the highest upstaging rate at 35.3% (95%CI: 21.8-48.7%) and 40.9% (95%CI: 35.6-46.2%). Lymph node involvement resulted in an upstaging rate of 8.7% (95%CI: 6.2-11.3%). Tumor was identified in uterus, cytology, peritoneal biopsies, omentum and appendix in 6.2% (95%CI: 1.8-10.7%), 18.4% (95%CI: 13.8-22.9%), 9.7% (95%CI: 3.8-15.6%), 5.2% (95%CI: 1.7-8.8%) and 3.6% (95%CI: 0.0-7.5%) of EOC patients. The corresponding upstaging rates were 5.9% (95%CI: 1.4-10.4%), 8.5% (95%CI: 1.8-15.2%), 3.5% (95%CI: 1.0-6.0%), 3.9% (95%CI: 1.4-6.3%) and 1.6% (95%CI: 0.0-3.4%), respectively. CONCLUSION: The attributive value of comprehensive surgical staging in clinically early-stage EOC patients remains substantial, particularly in serous and high grade tumors.

Prognostic value of radiological recurrence patterns in ovarian cancer.

OBJECTIVE: To study the prognostic value of CT assessed recurrence patterns on survival outcomes in women with epithelial ovarian cancer. METHODS: CT scans were systematically re-evaluated on predefined anatomical sites for the presence of tumor in all 89 patients diagnosed with epithelial ovarian cancer between January 2008 and December 2013 who underwent cytoreductive surgery at our institution and developed a recurrence. A Cox proportional hazard analysis was used to test the effect of recurrence patterns on survival. RESULTS: The median survival time for patients grouped as predominantly intraperitoneal (n = 62), hematogenous (n = 13) or lymphatic (n = 14) recurrence was 25.8 (95% CI 18.4-33.2), 27.6 (95% CI 18.5-36.6) and 52.9 months (95% CI 42.1-63.7), respectively. Univariate Cox regression analysis identified the following prognostic factors: lymphatic recurrence pattern (HR 0.42, 95% CI 0.21-0.85), ascites at diagnosis (HR 2.35, 95% CI 1.46-3.79), residual tumor at initial surgery (HR 2.16, 95% CI 1.36-3.44) and FIGO stage (I-IIIB: HR 0.59, 95% CI 0.33-1.06). The median time to recurrence was 19.5 month for patients after complete debulking surgery, 13.1 months for patients with residual disease ≤1 cm and 8.2 months for patients with residual disease >1 cm after surgery (P < 0.001). No differences in recurrence patterns between patients with complete and incomplete surgery were found. CONCLUSIONS: Prolonged survival rates were found in ovarian cancer patients with a predominantly lymphatic recurrence compared to patients with a predominantly peritoneal or hematogenous recurrence. Completeness of surgery was associated with time to recurrence. Classification of recurrence patterns can help counsel patients on their prognosis at the time of recurrence.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) for assessing tumour resectability in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer.

BACKGROUND: Ovarian cancer is the leading cause of death from gynaecological cancer in developed countries. Surgery and chemotherapy are considered its mainstay of treatment and the completeness of surgery is a major prognostic factor for survival in these women. Currently, computed tomography (CT) is used to preoperatively assess tumour resectability. If considered feasible, women will be scheduled for primary debulking surgery (i.e. surgical efforts to remove the bulk of tumour with the aim of leaving no visible (macroscopic) tumour). If primary debulking is not considered feasible (i.e. the tumour load is too extensive), women will receive neoadjuvant chemotherapy to reduce tumour load and subsequently undergo (interval) surgery. However, CT is imperfect in assessing tumour resectability, so additional imaging modalities can be considered to optimise treatment selection. OBJECTIVES: To assess the diagnostic accuracy of fluorodeoxyglucose-18 (FDG) PET/CT, conventional and diffusion-weighted (DW) MRI as replacement or add-on to abdominal CT, for assessing tumour resectability at primary debulking surgery in women with stage III to IV epithelial ovarian/fallopian tube/primary peritoneal cancer. SEARCH METHODS: We searched MEDLINE and Embase (OVID) for potential eligible studies (1946 to 23 February 2017). Additionally, ClinicalTrials.gov, WHO-ICTRP and the reference list of all relevant studies were searched. SELECTION CRITERIA: Diagnostic accuracy studies addressing the accuracy of preoperative FDG-PET/CT, conventional or DW-MRI on assessing tumour resectability in women with advanced stage (III to IV) epithelial ovarian/fallopian tube/primary peritoneal cancer who are scheduled to undergo primary debulking surgery. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts for relevance and inclusion, extracted data and performed methodological quality assessment using QUADAS-2. The limited number of studies did not permit meta-analyses. MAIN RESULTS: Five studies (544 participants) were included in the analysis. All studies performed the index test as replacement of abdominal CT. Two studies (366 participants) addressed the accuracy of FDG-PET/CT for assessing incomplete debulking with residual disease of any size (> 0 cm) with sensitivities of 1.0 (95% CI 0.54 to 1.0) and 0.66 (95% CI 0.60 to 0.73) and specificities of 1.0 (95% CI 0.80 to 1.0) and 0.88 (95% CI 0.80 to 0.93), respectively (low- and moderate-certainty evidence). Three studies (178 participants) investigated MRI for different target conditions, of which two investigated DW-MRI and one conventional MRI. The first study showed that DW-MRI determines incomplete debulking with residual disease of any size with a sensitivity of 0.94 (95% CI 0.83 to 0.99) and a specificity of 0.98 (95% CI 0.88 to 1.00) (low- and moderate-certainty evidence). For abdominal CT, the sensitivity for assessing incomplete debulking was 0.66 (95% CI 0.52 to 0.78) and the specificity 0.77 (95% CI 0.63 to 0.87) (low- and low-certainty evidence). The second study reported a sensitivity of DW-MRI of 0.75 (95% CI 0.35 to 0.97) and a specificity of 0.96 (95% CI 0.80 to 1.00) (very low-certainty evidence) for assessing incomplete debulking with residual disease > 1 cm. In the last study, the sensitivity for assessing incomplete debulking with residual disease of > 2 cm on conventional MRI was 0.91 (95% CI 0.59 to 1.00) and the specificity 0.97 (95% CI 0.87 to 1.00) (very low-certainty evidence). Overall, the certainty of evidence was very low to moderate (according to GRADE), mainly due to small sample sizes and imprecision. AUTHORS' CONCLUSIONS: Studies suggested a high specificity and moderate sensitivity for FDG-PET/CT and MRI to assess macroscopic incomplete debulking. However, the certainty of the evidence was insufficient to advise routine addition of FDG-PET/CT or MRI to clinical practice..In a research setting, adding an alternative imaging method could be considered for women identified as suitable for primary debulking by abdominal CT, in an attempt to filter out false-negatives (i.e. debulking, feasible based on abdominal CT, unfeasible at actual surgery).

High-resolution T2-weighted cervical cancer imaging: a feasibility study on ultra-high-field 7.0-T MRI with an endorectal monopole antenna.

OBJECTIVES: We studied the feasibility of high-resolution T2-weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of 4.7-mm thickness. METHODS: A feasibility study on 20 stage IB1-IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B1+ shimming, T2-weighted turbo spin echo sequences were completed. RESULTS: Patients had stage IB1 (n = 9), IB2 (n = 4), IIA1 (n = 1) or IIB (n = 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0-5) and 0 (range, 0-2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T2-weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B1 interference, excessive B1 under the external antennae and SENSE reconstruction. CONCLUSIONS: High-resolution T2-weighted 7.0-T MRI of stage IB1-IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients. KEY POINTS: • High resolution T 2 -weighted 7.0-T MRI of the inner female pelvis is challenging • We demonstrate a feasible approach for T 2 -weighted 7.0-T MRI of cervical cancer • An endorectal monopole receive antenna is well tolerated by participants • The endorectal antenna did not lead to adverse events or session discontinuation.

Preoperative sentinel node mapping with (99m)Tc-nanocolloid SPECT-CT significantly reduces the intraoperative sentinel node retrieval time in robot assisted laparoscopic cervical cancer surgery.

OBJECTIVE: To compare preoperative sentinel node (SN) mapping with planar lymphoscintigraphy (LSG) to single photon emission computed tomography with computed tomography (SPECT-CT) for differences in intraoperative SN retrieval time in surgically treated cervical cancer patients. METHODS: In cervical cancer patients planned for radical surgery, one day preoperatively, 220-290 MBq technetium-99m-nanocolloid was injected intracervically in four quadrants. Subsequent SN mapping was performed by either LSG (09.2009-03.2011) or SPECT-CT (03.2011-10.2012). The SN resection, by four armed robot assisted laparoscopy, was based on blue dye and technetium-99m and followed by pelvic lymph node dissection. Timing of perioperative care, including SN procedure times, was prospectively registered. RESULTS: Out of the 62 subjects included, 33 (53.2%) underwent LSG and 29 (46.8%) SPECT-CT. No significant differences in baseline characteristics were observed. Bi- and unilateral SN visualization rates were 75.8% and 15.2% for LSG versus 86.2% and 6.9% for SPECT-CT (p=0.299 and p=0.305, respectively). Intraoperative bi/unilateral SN detection occurred in 84.8% and 9.1% of LSG subjects versus 89.7% and 3.4% for SPECT-CT (p=0.573 and p=0.616). Correlation in SN location between mapping and surgery was low for LSG (Spearman ρ=0.098; p=0.449) but high for SPECT-CT (ρ=0.798; p<0.001). Bilateral intraoperative SN retrieval times for LSG and SPECT-CT were 75.4±33.5 and 50.1±15.6 min, resulting in an average difference of 25.4 min (p=0.003). CONCLUSION: SPECT-CT significantly reduces intraoperative SN retrieval with a clinically relevant time compared to LSG. The trend towards better bilateral visualization rates and significantly higher anatomical concordance may partly explain the observed difference in SN retrieval time.

Detection of cervical cancer recurrence during follow-up: a multivariable comparison of 9 frequently investigated serum biomarkers.

OBJECTIVE: To assess the diagnostic accuracy and model the optimal combination of commonly studied serum biomarkers aimed at identifying recurrence in cervical cancer patients. METHODS: From a systematic literature search, nine biomarkers (CA-15.3, CA-125, CEA, CYFRA 21-1, hsCRP, IL-6, SCC-Ag, TNF-α and VEGF) were selected for a serum analysis. Samples were derived from a historical cervical cancer cohort. Subjects with serum samples stored in a biobank were included when quality criteria were met, and one sample preceding and at least one following primary treatment were available. In case of recurrence, two additional post-recurrence samples were analyzed. Biomarker serum levels were quantified by enzyme linked or chemiluminescence microparticle immunoassays. Logistic regression and receiver operating curve analysis were employed for selection, modeling and comparison on the diagnostic accuracy of the tested biomarkers. RESULTS: 205 samples were analyzed from 75 subjects, of whom 19 (25.3%) had a recurrence. The area under the curve (AUC) of CA-15.3, CA-125, CEA, CYFRA 21-1, IL-6, TNF-α and VEGF were all <0.750. Only SCC-Ag and hsCRP were included in the final model with an AUC of 0.822 (95% CI: 0.744-0.900) and 0.831 (95% CI: 0.758-0.905) respectively. Combined AUC was 0.870 (95% CI: 0.805-0.935). Rises in SCC-Ag and hsCRP significantly increased the odds for recurrence. Each ng/ml of SCC-Ag increase, related to an odds ratio (OR) of 1.117 (95% CI: 1.039-1.200). Comparably, the OR for hsCRP (in mg/ml) was 1.025 (95% CI: 1.012-1.038). CONCLUSION: Combined testing of SCC-Ag and hsCRP yields the highest detection rate of disease recurrence during cervical cancer follow-up.

Learning curve and factors influencing successful robot-assisted bilateral sentinel lymph node mapping in early-stage cervical cancer: an observational cohort study.

OBJECTIVES: To evaluate whether a learning curve affects the bilateral sentinel lymph node (SLN) detection in early-stage cervical cancer. METHODS: All patients with FIGO (2018) stage IA1-IB2 or IIA1 cervical cancer who had undergone robot-assisted SLN mapping performed with a combination of preoperative technetium-99m nanocolloids (including preoperative imaging) and intraoperative blue dye were retrospectively included. Risk-adjusted cumulative sum (RA-CUSUM) analysis was used to determine if a learning curve based on bilateral SLN detection existed in this cohort. RESULTS: A total of 227 cervical cancer patients were included. In 98.2% of patients (223/227) at least one SLN was detected. The bilateral SLN detection rate was 87.2% (198/227). Except for age (OR 1.06 per year, 95%CI 1.02-1.09), no significant risk factors for non-bilateral SLN detection were found (e.g., prior conization, BMI or FIGO stage). The RA-CUSUM analysis showed no clear learning phase during the first procedures and cumulative bilateral detection rate remained at least 80% during the entire inclusion period. CONCLUSIONS: In this single-institution experience, we observed no learning curve affecting robot-assisted SLN mapping using a radiotracer and blue dye in early-stage cervical cancer patients, with stable bilateral detection rates of at least 80% when adhering to a standardized methodology.

Feasibility of a drop-in γ-probe for radioguided sentinel lymph detection in early-stage cervical cancer.

BACKGROUND: Minimally invasive radioguided sentinel lymph node (SLN) procedures, increasingly performed with robot-assisted laparoscopy, can benefit from using a drop-in γ-probe instead of the conventional rigid laparoscopic γ-probe. We evaluated the safety and feasibility of a tethered drop-in γ-probe system for SLN detection in patients with early-stage cervical cancer. METHODS: Ten patients with FIGO stage IA - IB2 or IIA1 cervical cancer scheduled for robot-assisted laparoscopic SLN procedure were included. All patients underwent preoperative 240 MBq technetium-99m nanocolloid (99mTc) injection and SPECT/CT imaging. Intraoperatively the tethered drop-in γ-probe SENSEI® (Lightpoint Medical Ltd, Chesham, UK) was used for probe guided SLN detection, subsequently confirmed by the standard rigid laparoscopic γ-probe. Sentinel lymph node detection rates and anatomical SLN location were assessed. Surgeon questionnaires were used to assess usability. RESULTS: In all patients at least one SLN was successfully resected under guidance of the drop-in γ-probe (overall detection rate: 100%). Bilateral SLN detection rate with the drop-in γ-probe was 80%. Of the two patients with unilateral SLN detection only, one presented with an atypical SLN location at the aortic bifurcation that was detected only on SPECT/CT. The other patient had failed unilateral 99mTc uptake. Combined use of preoperative SPECT/CT and drop-in γ-probe resulted in a bilateral detection rate of 90%. Similar to the drop-in γ-probe, overall and bilateral SLN detection rate of the rigid γ-probe was 100% and 80%, respectively. No significant discrepancy existed between the count rate of the drop-in and rigid laparoscopic γ-probe (p = 0.69). In total 21 SLN's were detected with the drop-in γ-probes including all three tumor positive nodes. Because of wristed articulation of the robotic tissue grasper and possibility of autonomous probe control by the surgeon, maneuverability and control with the drop-in γ-probe were highly rated in surgeon questionnaires. No adverse events related to the intervention occurred. CONCLUSIONS: Sentinel lymph node detection with a drop-in γ-probe is safe and feasible in patients with early-stage cervical cancer. Use of the drop-in γ-probe enhances maneuverability and surgical autonomy during robot-assisted SLN detection. Trial registration Netherlands Trial Registry, NL9358. Registered 23 March 2021, https://www.trialregister.nl/trial/9358 .

Indocyanine green versus technetium-99m with blue dye for sentinel lymph node detection in early-stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: The fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early-stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached. AIMS: We aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium-99m (99m Tc) with blue dye. METHODS AND RESULTS: We searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99m Tc with blue dye in early-stage cervical cancer. The overall and bilateral detection rates were pooled with random-effects meta-analyses. From 118 studies retrieved seven studies (one cross-sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99m Tc with blue dye. Meta-analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99m Tc with blue dye; 90.3% (95%CI, 79.8-100.0%) with ICG versus 73.5% (95%CI, 66.4-80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3-28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI -0.8-27.3%). CONCLUSION: ICG appears to provide higher bilateral SLN detection rates compared to 99m Tc with blue dye in patients with early-stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, the quality of evidence is too low to provide strong recommendations and directly omit the combined approach of 99m Tc with blue dye.

Fluorescent Indocyanine Green versus Technetium-99m and Blue Dye for Bilateral SENTinel Lymph Node Detection in Stage I-IIA Cervical Cancer (FluoreSENT): protocol for a non-inferiority study.

INTRODUCTION: Nowadays, two predominant methods for detecting sentinel lymph nodes (SLNs) in cervical cancer are in use. The most conventional method is a combination of a radiotracer, technetium-99m (99mTc) and blue dye. More recently, another method for SLN mapping using indocyanine green (ICG) is becoming widely accepted. ICG is a fluorescent dye, visualised intraoperatively with near-infrared (NIR) fluorescence imaging, providing real-time visual navigation. The presumed advantages of ICG over 99mTc, that is, being cheaper, non-radioactive and logistically more attractive, are only valuable if its detection rate proves to be at least non-inferior. Before omitting the well-functioning and evidence-based combined approach of 99mTc and blue dye, we aim to provide prospective evidence on the non-inferiority of ICG with NIR fluorescence imaging. METHODS AND ANALYSIS: We initiated a prospective non-inferiority study with a paired comparison of both SLN methods in a single sample of 101 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB2 or IIA1 cervical cancer receiving primary surgical treatment. All patients undergo SLN mapping with ICG and NIR fluorescence imaging in adjunct to mapping with 99mTc (including single photon emission computed tomography with X-ray computed tomography (SPECT/CT)) and blue dye. Surgeons start SLN detection with ICG while being blinded for the preoperative outcome of SPECT/CT to avoid biased detection with ICG. Primary endpoint of this study is bilateral SLN detection rate of both methods (ie, detection of at least one SLN in each hemipelvis). Since we compare strategies for SLN mapping that are already applied in current daily practice for different types of cancer, no additional risks or burdens are expected from these study procedures. ETHICS AND DISSEMINATION: The current study is approved by the Medical Ethics Research Committee Utrecht (reference number 21-014). Findings arising from this study will be disseminated in peer-reviewed journals, academic conferences and through patient organisations. TRIAL REGISTRATION NUMBER: NL9011 and EudraCT 2020-005134-15.

The influence of the b-value combination on apparent diffusion coefficient based differentiation between malignant and benign tissue in cervical cancer.

PURPOSE: To analyze the influence of different b-value combinations on apparent diffusion coefficient (ADC)-based differentiation of known malignant and benign tissue in cervical cancer patients. MATERIALS AND METHODS: A total of 35 patients with stage IB1, IB2, IIA cervical cancer underwent a 3.0T MRI scan prior to radical hysterectomy and pelvic lymph node dissection. Conventional T1- and T2-weighted sequences and a diffusion-weighted sequence (b = 0, 150, 500, 1000 seconds/mm(2)) were performed. Regions-of-interest (ROI) were drawn on ADC maps derived from five different b-value combinations (0, 500; 0, 150, 500; 0, 1000; 0, 150, 500, 1000; 150, 500, 1000 seconds/mm(2)). The influence of the b-value combination on ADC-based differentiation of benign and malignant tissue was analyzed using receiver-operating-characteristics curves. RESULTS: For all b-value combinations, ADCs were significantly lower (P < 0.001) in cervical malignancies (1.15 +/- 0.21.10(-3); 1.10 +/- 0.21.10(-3); 0.97 +/- 0.18.10(-3); 0.97 +/- 0.23.10(-3) and 0.85 +/- 0.18.10(-3) mm(2)/second respectively to the aforementioned b-value combinations) than in benign cervix (2.08 +/- 0.31.10(-3); 2.00 +/- 0.29.10(-3); 1.62 +/- 0.23.10(-3); 1.54 +/- 0.21.10(-3) and 1.42 +/- 0.22.10(-3) mm(2)/second respectively). The diagnostic accuracy was high for all b-value combinations and without statistical differences between the combinations. CONCLUSION: ADC-based differentiation of benign from malignant cervical tissue is independent of the tested b-value combinations. The results support the inclusion and possible pooling of studies using different b-value combinations in meta-analyses on ADC-based tissue differentiation in cervical cancer.

99mTc-Nanocolloid SPECT/MRI Fusion for the Selective Assessment of Nonenlarged Sentinel Lymph Nodes in Patients with Early-Stage Cervical Cancer.

UNLABELLED: We aimed to explore the accuracy of (99m)Tc SPECT/MRI fusion for the selective assessment of nonenlarged sentinel lymph nodes (SLNs) for diagnosing metastases in early-stage cervical cancer patients. METHODS: We consecutively included stage IA1-IIB1 cervical cancer patients who presented to our tertiary referral center between March 2011 and February 2015. Patients with enlarged lymph nodes (short axis ≥ 10 mm) on MRI were excluded. Patients underwent an SLN procedure with preoperative (99m)Tc-nanocolloid SPECT/CT-based SLN mapping. When fused datasets of the SPECT and MR images were created, SLNs could be identified on the MR image with accurate correlation to the histologic result of each individual SLN. An experienced radiologist, masked to histology, retrospectively reviewed all fused SPECT/MR images and scored morphologic SLN parameters on a standardized case report form. Logistic regression and receiver-operating curves were used to model the parameters against the SLN status. RESULTS: In 75 cases, 136 SLNs were eligible for analysis, of which 13 (9.6%) contained metastases (8 cases). Three parameters-short-axis diameter, long-axis diameter, and absence of sharp demarcation-significantly predicted metastatic invasion of nonenlarged SLNs, with quality-adjusted odds ratios of 1.42 (95% confidence interval [CI], 1.01-1.99), 1.28 (95% CI, 1.03-1.57), and 7.55 (95% CI, 1.09-52.28), respectively. The area under the curve of the receiver-operating curves combining these parameters was 0.749 (95% CI, 0.569-0.930). Heterogeneous gadolinium enhancement, cortical thickness, round shape, or SLN size, compared with the nearest non-SLN, showed no association with metastases (P= 0.055-0.795). CONCLUSION: In cervical cancer patients without enlarged lymph nodes, selective evaluation of only the SLNs-for size and absence of sharp demarcation-can be used to noninvasively assess the presence of metastases.

The effect of personal medical history and family history of cancer on the uptake of risk-reducing salpingo-oophorectomy.

Women with an increased lifetime risk of ovarian cancer are advised to undergo risk-reducing salpingo-oophorectomy (RRSO) to reduce risk of adnexal cancer. We investigated the uptake of RRSO and evaluated the influence of personal medical history of (breast) cancer, risk-reducing mastectomy (RRM) and family history of ovarian and/or breast cancer on the RRSO decision. This single center retrospective observational cohort study was performed in a tertiary multidisciplinary clinic for hereditary cancer of the University Medical Centre Utrecht, The Netherlands. Women ≥35 years old with an estimated lifetime risk of ovarian cancer ≥10%, who had completed childbearing, were eligible for RRSO. Uptake and timing of RRSO were analyzed. Influence of personal medical history and family history on RRSO decision making, were evaluated with logistic regression. The study population consisted of 218 women (45.0% BRCA1 mutation carrier, 28.0% BRCA2 mutation carrier, 27.0% with familial susceptibility) with 87.2% RRSO uptake. The median age at RRSO was 44.5 (range 28-73) years. Of the women undergoing RRSO, 78.3% needed ≤3 consultations to reach this decision. Multivariable analysis showed a significant difference in RRSO uptake for women with a history of RRM [OR 3.66 95% CI (1.12-11.98)], but no significant difference in women with a history of breast cancer [OR 1.38 95% CI (0.50-3.79)], nor with a family history of ovarian and/or breast cancer [OR 1.10 95% CI (0.44-2.76)]. We conclude that RRSO counseling, without the alternative of screening, is effective. The uptake is increased in women with a history of RRM.

99mTc SPECT/CT Versus Planar Lymphoscintigraphy for Preoperative Sentinel Lymph Node Detection in Cervical Cancer: A Systematic Review and Metaanalysis.

UNLABELLED: We aimed to compare SPECT/CT and lymphoscintigraphy on overall and bilateral sentinel lymph node (SLN) detection in cervical cancer patients. METHODS: A systematic search was performed on August 1, 2014, in PubMed, Embase, Scopus, and the Cochrane library. The syntax was based on synonyms of the terms cervical cancer, SPECT/CT, and lymphoscintigraphy. Retrieved articles were screened on their title/abstract and considered eligible when an SLN procedure was performed using both imaging modalities and if detection results were reported. Two independent reviewers assessed all included studies on methodologic quality using QUADAS-2. Studies were pooled on their odds ratios (ORs) with a random-effects model. RESULTS: The search yielded 962 unique articles, of which 8 were ultimately included. The studies were recent retrospective or prospective cohort studies of limited size (n = 7-51) but sufficient methodologic quality. The median overall detection (≥1 SLN in a patient) was 98.6% for SPECT/CT (range, 92.2%-100.0%) and 85.3% for lymphoscintigraphy (range, 70.0%-100.0%). This corresponded to a pooled overall SLN detection OR of 2.5 (95% CI, 1.2-5.3) in favor of SPECT/CT. The reported median bilateral detection (≥1 SLN in each hemipelvis) was 69.0% for SPECT/CT (range, 62.7%-79.3%) and 66.7% for lymphoscintigraphy (range, 56.9%-75.8%), yielding a pooled OR of 1.2 (95% CI, 0.7-2.1). No significant difference in the number of visualized SLNs was observed at a pooled ratio of 1.2 (95% CI, 0.9-1.6). CONCLUSION: In cervical cancer patients, preoperative SLN imaging with SPECT/CT results in superior overall SLN detection in comparison with planar lymphoscintigraphy.

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients.

AIM: Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. METHODS: All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. RESULTS: Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. CONCLUSION: Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years.