Michael Burling

Sentinel lymph node biopsy at robotic-assisted hysterectomy for atypical hyperplasia and endometrial cancer

Lymph node (LN) evaluation in endometrial cancer is controversial. Sentinel lymph node biopsy (SLNB) allows for an accurate nodal assessment while minimising the risks of a full pelvic lymph node dissection (PLND). The aims of this study are to examine the characteristics and peri-operative outcomes of women with atypical hyperplasia (AH) or endometrial cancer undergoing robotic-assisted hysterectomy (RAH) ± SLNB or PLND; to examine the utilisation, feasibility and role of SLNB and compare their peri-operative outcomes. Retrospective cohort study from December 2018 to February 2021 of women who underwent RAH ± LN assessment for endometrial cancer or AH. 115 women underwent RAH. 59% had SLNB, 29% had no LN assessment, and 12% had PLND. The final diagnosis was mostly early stage low-grade disease; Stage 1A-50%, Grade 1 endometrioid adenocarcinoma (EAC)-56%. The detection rate was 90%. There was a statistically significant trend towards performing SLNB over time (P value 0.004). There was a statistically shorter length of stay, less estimated blood loss, and shorter surgical duration in the SLNB cohort, compared to the no LN assessment cohort (P values 0.02, 0.01, and 0.03, respectively). There was statistically significant less estimated blood loss and surgical duration in the SLNB compared to the PLND cohort (P values 0.03 and 0.001, respectively). SLNB at RAH was utilised and feasible. It was safe with a low complication rate and had advantages compared to PLND cohort. SLNB should be considered in suitable selected women undergoing surgery for endometrial cancer or AH.

The utilisation of sentinel lymph node biopsy for endometrial cancer in Australia and New Zealand

AimsThe aim of this study was to identify to what extent the sentinel lymph node (SLN) technique is utilised by gynaecological oncologists in Australia and New Zealand, identifying the techniques used, any barriers to uptake, and management of isolated tumour cells (ITCs) and micrometastases.Materials and methodsWe conducted an online survey of all practising gynaecological oncologists in Australia and New Zealand. They were asked whether they utilised SLN biopsy and in what circumstances, how they managed non‐mapping and how their multidisciplinary team managed small volume disease. Those who did not were asked to identify their concerns with the procedure, reasons for non‐uptake and their alternate technique.ResultsWe surveyed 63 gynaecological oncologists of whom 59 were practising, and 48 (81%) responded. Six members (11%) do not utilise SLN biopsy, and 42 (89%) do. Areas where clinicians differ in practice are those areas that are most controversial and include the use of SLN biopsy in complex atypical hyperplasia, the management of ITCs and micrometastases and procedures on unilateral or bilateral non‐mapping. Those who do not utilise the technique cite concerns about the false‐negative rate, equipment and training issues.ConclusionsThe utilisation of SLN biopsy in endometrial cancer is well established in Australia and New Zealand, with similar practices and concerns to those of other international groups.

Clinical Trial Protocol for HyNOVA: Hyperthermic and Normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial OVArian, fallopian tube and primary peritoneal cancer (ANZGOG1901/2020)

Ovarian cancer is the most lethal gynecological cancer, causing over 200,000 deaths worldwide in 2020. Initial standard treatment for primary ovarian cancer is optimal cytoreductive surgery (CRS) preceded and/or followed by intravenous platinum-based chemotherapy. However, most women develop recurrence within the peritoneal cavity and die of disease. Results of the OVIHIPEC 1 trial (2018) showed improved survival of 34% when hyperthermic intraperitoneal chemotherapy (HIPEC) was given immediately following interval-CRS in women with stage III disease. However, it is unknown if the effect of HIPEC is due to hyperthermia, one extra cycle of intraperitoneal (IP) chemotherapy, or other factors. There is also concern that hyperthermia might be associated with an increase in adverse events (AEs) due to a heightened systemic inflammatory response. HyNOVA is a seamless, multi-stage randomized study that attempts to answer these questions by comparing HIPEC to normothermic intraperitoneal chemotherapy (NIPEC), focusing on safety (stage 1), then assessing activity (stage 2) and effectiveness (stage 3). In this initial study, we hypothesize that NIPEC will result in a lower rate of severe AEs compared to HIPEC. This initial stage of HyNOVA is a phase II study of 80 women with International Federation of Gynaecology and Obstetrics stage III epithelial ovarian cancer, with at least stable disease following 3-4 cycles of neoadjuvant chemotherapy, achieving interval-CRS to <2.5 mm residual disease. Participants are randomized 1:1 to receive IP cisplatin 100 mg/m² for 90 minutes either as HIPEC, heated to 42°C (41.5°C-42.5°C), or NIPEC, at 37°C (36.5°C-37.5°C). The primary outcome is the proportion of AEs ≥ grade 3 occurring within 90 days. Secondary outcomes are AE of interest, surgical morbidity, patient reported outcomes, resource allocation, feasibility, progression-free survival and overall survival. AEs are measured using both CTCAE v5.0 and Clavien-Dindo classification, particularly infection, pain, bowel dysfunction, and anemia. Tertiary outcomes are potential predictive biomarkers measured before and after HIPEC/NIPEC including circulating cell-free tumor DNA, tissue factors, and systemic inflammatory markers. There are 4 participating Australian sites with experience in CRS and HIPEC for peritoneal malignancy. HyNOVA is funded by an MRFF grant (APP1199155). ANZCTR Identifier: ACTRN12621000269831.