Sentinel lymph node procedure in patients with recurrent vulvar squamous cell carcinoma:a proposed protocol for a multicentre observational study

BACKGROUND: Standard groin treatment in recurrent vulvar cancer consists of uni- or bilateral inguinofemoral lymphadenectomy (IFL), whereas in the primary setting women with selected unifocal tumours will undergo a sentinel lymph node (SLN) procedure. The SLN procedure results in fewer short and long-term sequelae compared to IFL, but some concerns must first be considered. Lymph drainage of the vulvar region can be affected by a previous surgery, which might reduce the number of detectable SLN nodes (feasibility) but increase the chance of encountering aberrant lymph drainage patterns such as bilateral SLNs in lateral tumours or SLNs at unexpected locations. Therefore, the SLN procedure potentially carries a higher risk of groin recurrence if a tumour positive node is not retrieved, but may also improve outcomes for women with aberrant drainage patterns. Since the relative benefits and drawbacks of the SLN procedure are still unclear we will investigate the safety of the SLN procedure in women with a first recurrent vulvar cancer. In a simultaneously started registration study we prospectively gather information on women with a first recurrence of vulvar cancer ineligible for the SLN procedure. METHOD: In this prospective multicentre observational study all women with a first recurrence of vulvar cancer will be asked to consent to the collection of information on their diagnostics, treatment and outcome, and to complete quality of life and lymph oedema questionnaires. Women with unifocal tumours smaller than 4 cm and unsuspicious groin nodes will be offered the SLN procedure, with follow-up every 3 months together with imaging at 6 and 12 months when the SLN is tumour negative. The primary outcome is groin recurrence within 2 years of initial surgery. A total of 150 women with negative SLNs will be required to demonstrate safety, a stopping rule will apply and an extensive statistical analysis has been designed. DISCUSSION: Should the SLN procedure prove feasible and safe in recurrent vulvar cancer, it will be available for implementation in clinics worldwide. The inclusion of women ineligible for the SLN procedure in the current prospective study will help to bridge knowledge gaps and define future research questions. TRIAL REGISTRATION: Medical Ethical Committee approval number NL70149.078.19 (trial protocol version 2.0, date March 2nd, 2020). Affiliation: Erasmus Medical Centre. Dutch trial register NL8467. Date of registration 19.03.2020

Relevance of routine pathology review in cervical carcinoma

To determine the impact of pathology review on the management of patients with cervical carcinoma, 264 reports of pathology review from 230 patients referred to Erasmus MC (2010–2012) were studied retrospectively. Discrepancies between pathologic diagnoses were classified as ‘major’ if they led to changes in treatment, and as ‘minor’ where there was no change. Patient and tumor characteristics were analyzed to identify the factors influencing these discrepancies. Fifty-eight (25.2%) discrepancies were identified; 28 (12.2%) were major, these resulted frequently from missing essential information, or discordant assessment of tumor invasion. Pathology review prevented under-treatment of 3.5%, over-treatment of 1.3%, treatment for incorrect malignancy of 1.3%, and enabled definitive treatment of 6.1% of patients. This highlights the importance of pathology review for appropriate management. Major discrepancies were rare (1%) for patients with macroscopic tumor and histologic diagnosis of squamous cell carcinoma (n = 100). For these patients, yield of pathology review may be limited

Hyperspectral imaging for the in vivo detection of ovarian cancer

Introduction For women diagnosed with advanced-stage epithelial ovarian cancer, complete cytoreductive surgery (CRS) is the most powerful independent parameter for prolonged survival. An intraoperative imaging technique to detect tumor deposits could help achieve complete CRS. Hyperspectral imaging (HSI) provides information on tissue composition, including tissue oxygenation, hemoglobin-, and tissue water and fat indices. In an earlier ex-vivo study it was shown that HSI can be used for ex-vivo tumor detection. Currently, we are evaluating whether HSI can be used in-vivo to distinguish tumor from healthy tissue.Methods HSI data of healthy and tumorous peritoneum, omentum, ovary, and mesentery were obtained in-vivo and preprocessed by image calibration and glare removal. The data were correlated to histopathology and used to train classifiers. The ability to delineate tumorous from healthy tissues was determined using leave-one-out cross-validation.Results A total of 18 images from 12 patients were included. In total 302.258 data points were extracted based on the knowledge of the surgeons and histopathological information. Our data shows that different organs that are affected by ovarian cancer yield different spectra. Additionally, we observe a difference in the spetra of tumor and non-tumor tissue.Conclusion/Implications HSI enables the classification of various tissue types, including tumor and non-tumor tissue. To improve classification outcomes, it is crucial to obtain more data and to make separate groups of healthy and tumorous tissues for each of these tissue types. HSI is a promising technique to differentiate between healthy tissue and ovarian cancer lesions and eventually help surgeons to achieve complete CRS

Survival of Women with Advanced Stage Cervical Cancer:Neo-Adjuvant Chemotherapy Followed by Radiotherapy and Hyperthermia versus Chemoradiotherapy

Aim: To investigate and compare overall survival (OS), disease-free survival (DFS) and toxicity of women who underwent either chemoradiotherapy with or without prior lymph node debulking or upfront chemotherapy followed by radiotherapy and hyperthermia (triple therapy) for locally advanced cervical cancer (LACC) to identify a potential role for triple therapy. Methods: Women with histologically proven LACC and with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 and IIA2 to IVA were included. Cox regression analyses were used for calculating hazard ratios and to adjust for confounding variables. A multivariable logistic regression analysis was used to examine the influence of covariates on toxicity. Results: A total of 370 patients were included of whom 58% (n = 213) received chemoradiotherapy (CRT), 18% (n = 66) received node-debulking followed by chemoradiotherapy (LND-CRT) and 25% (n = 91) received triple therapy (TT). Five-year OS was comparable between the three treatment groups, with 53% (95% confidence interval 46–59%) in the CRT group, 45% (33–56%) in the LND-CRT group and 53% (40–64%) in the TT group (p = 0.472). In the adjusted analysis, 5-year OS and DFS were comparable between the three treatment groups. No chemotherapy-related differences in toxicity were observed. Conclusion: This study suggests that the toxicity and survival of TT is similar to CRT or LND-CRT.</p

Cytoreductive Surgery with the PlasmaJet Improved Quality-of-Life for Advanced Stage Ovarian Cancer Patients

Background: Knowledge of quality-of-life after cytoreductive surgery is important to counsel patients with advanced-stage epithelial ovarian cancer prior to surgery. The aim of this study was to determine whether the use of the PlasmaJet Surgical device during cytoreductive surgery has an effect on the quality-of-life of patients with advanced epithelial ovarian cancer. Methods: Data included in this prospective observational study were derived from the PlaComOv study, in which patients with advanced epithelial ovarian cancer were randomly assigned to have cytoreductive surgery with or without adjuvant use of the PlasmaJet. Quality-of-life was measured before surgery and one, six, 12, and 24 months after surgery with three questionnaires: the EORTC QLQ-C30, QLQ-OV28, and EQ-5D-5L. Results: Between 2018 and 2020, 326 patients were enrolled in the trial. The overall response rate was high, with the lowest response rate at 24 months of 77%. At 6 months, quality-of-life was higher in the intervention group (95%CI 0.009; 0.081, p = 0.045). At 12 months, quality-of-life was higher in the intervention group with fewer symptoms of fatigue, appetite loss, and diarrhea (95%CI 0.6; 10,0, p = 0.027); similarly, patients in the intervention group reported a better body image (95%CI −14.2; −3.0, p = 0.003) and a higher score on the visual analog scale (95%CI 1.99; 11.15, p = 0.005). At 24 months postoperatively, no further difference was found between the two groups except for pain (95%CI −12.9; −0.8, p = 0.027) and body image (95%CI −13.808; −0.733, p = 0.029). A higher quality-of-life in the intervention group was partially explained by the mediator ‘surgery outcome’. Conclusions: This study demonstrated knowledge of patients’ quality-of-life until two years after cytoreductive surgery. The use of the PlasmaJet Surgical device during cytoreductive surgery leads to a higher quality-of-life than conventional surgery with electrocoagulation alone. Even after adjustment for the mediator of surgical outcome, a higher quality-of-life was seen in patients who had surgery with the use of the PlasmaJet device.</p

Survival of Women with Advanced Stage Cervical Cancer:Neo-Adjuvant Chemotherapy Followed by Radiotherapy and Hyperthermia versus Chemoradiotherapy

Aim: To investigate and compare overall survival (OS), disease-free survival (DFS) and toxicity of women who underwent either chemoradiotherapy with or without prior lymph node debulking or upfront chemotherapy followed by radiotherapy and hyperthermia (triple therapy) for locally advanced cervical cancer (LACC) to identify a potential role for triple therapy. Methods: Women with histologically proven LACC and with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 and IIA2 to IVA were included. Cox regression analyses were used for calculating hazard ratios and to adjust for confounding variables. A multivariable logistic regression analysis was used to examine the influence of covariates on toxicity. Results: A total of 370 patients were included of whom 58% (n = 213) received chemoradiotherapy (CRT), 18% (n = 66) received node-debulking followed by chemoradiotherapy (LND-CRT) and 25% (n = 91) received triple therapy (TT). Five-year OS was comparable between the three treatment groups, with 53% (95% confidence interval 46–59%) in the CRT group, 45% (33–56%) in the LND-CRT group and 53% (40–64%) in the TT group (p = 0.472). In the adjusted analysis, 5-year OS and DFS were comparable between the three treatment groups. No chemotherapy-related differences in toxicity were observed. Conclusion: This study suggests that the toxicity and survival of TT is similar to CRT or LND-CRT.</p