Comparison of Weekly Paclitaxel Regimens in Recurrent Platinum-Resistant Ovarian Cancer: A Single Institution Retrospective Study.

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy.

Safety of vaginal surgery for early-stage cervical cancer: A retrospective multicenter cohort study.

OBJECTIVE: Abdominal Radical hysterectomy (ARH) with pelvic lymph node assessment is considered the standard treatment for early-stage cervical cancer. Accepted routes have previously included laparoscopic or robotic approaches (LRH). Laparoscopy-assisted vaginal or vaginal radical hysterectomy (LVRH) are performed in some centers. The objective of this study is to compare surgical and oncological outcomes of LVRH, to laparoscopic and abdominal approaches. DESIGN PATIENTS SETTING: A retrospective multicenter analysis of consecutive cervical cancer cases who underwent a radical hysterectomy between 2007 and 2017 in eleven regional cancer centers across Canada. MEASUREMENTS: A comparison of patients stratified by surgical technique was undertaken. T-test, Wilcoxon rank-sum and chi-square were used to compare patient characteristics. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across surgical groups. MAIN RESULTS: A total of 1071 patients with cervical cancer stage IA1 with lymphovascular invasion to stage IIIC (FIGO 2018) <4 cm were identified. Postoperative complication rate was lowest for women undergoing LVRH (9.1 %, vs 18.3 % and 22.1 % for minimally invasive and open respectively). During follow up, 114 women recurred, and 70 women died. 5-year recurrence-free survival was 85.4 % for LRH, 89.4 % for ARH and 92.2 % for LVRH. LVRH was not found to be associated with a higher risk of recurrence or death than ARH on multivariable analysis (aHR for recurrence 0.62, CI 0.21-1.77; aHR for death 0.63, CI 0.14-2.77) CONCLUSION: In this retrospective study, vaginal or laparoscopy-assisted vaginal radical hysterectomy for cervical cancer was associated with favorable perioperative and oncological outcomes.

Assessing minimally invasive simple hysterectomy in low risk cervical cancer: set up for the LASH trial.

After the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer. Recent studies assessed the role of a non-radical approach in low risk cervical cancer and showed no survival difference compared with radical hysterectomy. However, there is a gap in knowledge regarding the oncologic outcomes of minimally invasive simple hysterectomy in low risk cervical cancer. This review offers an overview of the current evidence on the role of the minimally invasive approach in low risk cervical cancer and raises the need for a new clinical trial in this setting.

Highlights from the 25th European Congress on Gynaecological Oncology in Barcelona: the ENYGO-IJGC Fellow Interviews.

In March 2024, 12 European Network of Young Gynae Oncologists-International Journal of Gynaecological Cancer (ENYGO-IJGC) Editorial Fellows conducted 10 interviews with senior opinion leaders on original and controversial topics in the field of gynecologic oncology presented during the 25th European Society of Gynaecological Oncology (ESGO) Congress in Barcelona, Spain. This article provides a summary and overview of the content of these discussions summarizing key points presented at the meeting. These selected interviews were chosen by consensus by the ENYGO-IJGC Editorial Fellows based on novelty and relevance to the field of gynecologic oncology.

De-escalation of surgical radicality for non-fertility preserving management in patients with early-stage cervical cancer: a systematic review.

OBJECTIVE: We sought to evaluate the oncologic outcomes of simple hysterectomy in patients with low-risk early-stage cervical cancer (tumors ≤2 cm with limited stromal invasion). METHODS: This study was registered in PROSPERO (registration number CRD42023433840) following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist. MEDLINE (through Ovid), EmMBASEbase, and Cochrane Central Register of Controlled Trials were searched from inception until June 2023. Randomized controlled trials and observational studies with two arms of comparison (simple hysterectomy with lymph node assessment vs radical hysterectomy with lymph node assessment) in patients with low-risk early-stage cervical cancer were considered. RESULTS: The search identified 1270 articles; eighteen studies were considered potentially eligible after removing duplicates, and four met the selection criteria. Three studies were randomized controlled trials, and the other was a retrospective cohort study. In total, 981 patients were included. There were 485 (49.4%) and 496 (50.6%) patients in the simple hysterectomy and radical hysterectomy groups, respectively. Simple hysterectomy with lymph node assessment was not associated with a higher risk of death at 5 years (RR 0.98, 95% CI: 0.31 to 3.10; I2=0%, two randomized controlled trials, 141 patients, for an absolute risk reduction of zero percentage points [95% CI -9.0 to 9.0]), pelvic recurrence at 3 years (97.5% and 97.8% for simple hysterectomy and radical hysterectomy, respectively, p=0.79), and overall recurrence at 3 years (95 %% and 100% for simple hysterectomy and radical hysterectomy, respectively, p=0.30). CONCLUSION: Simple hysterectomy with lymph node evaluation for low-risk early-stage cervical cancer is not associated with a detrimental effect on oncologic outcomes and has a better morbidity profile.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

HPV vaccination in Africa in the COVID-19 era: a cross-sectional survey of healthcare providers' knowledge, training, and recommendation practices.

Introduction: Although the burden of cervical cancer in Africa is highest, HPV vaccination coverage remains alarmingly low in this region. Providers' knowledge and recommendation are key drivers of HPV vaccination uptake. Yet, evidence about providers' knowledge and recommendation practices about the HPV vaccine against a backdrop of emerging vaccine hesitancy fueled by the COVID-19 pandemic is lacking in Africa. Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior training, the availability of the HPV vaccine in their practice, whether they recommended the HPV vaccine, and, if not, the reasons for not recommending it. Their knowledge about the HPV vaccine was assessed through self-reporting (perceived knowledge) and with three pre-tested knowledge questions (measured knowledge). Results: Of the 153 providers from 23 African countries who responded to the survey (mean age: 38.5 years, SD: 10.1), 75 (54.0%) were female and 97 (63.4%) were based In countries with national HPV immunization programs. Overall, 57 (43.8%) reported having received prior training on HPV vaccine education/counseling, and 40 (37.4%) indicated that the HPV vaccine was available at the facility where they work. Most respondents (109, 83.2%) reported recommending the HPV vaccine in their practice. Vaccine unavailability (57.1%), lack of effective communication tools and informational material (28.6%), and need for adequate training (28.6%) were the most commonly reported reasons for not recommending the HPV vaccine. While 63 providers (52.9%) reported that their knowledge about HPV vaccination was adequate for their practice, only 9.9% responded correctly to the 3 knowledge questions. Conclusion: To increase HPV vaccination coverage and counter misinformation about this vaccine in Africa, adequate training of providers and culturally appropriate educational materials are needed to improve their knowledge of the HPV vaccine and to facilitate effective communication with their patients and the community.

Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer.

BACKGROUND: Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking. METHODS: We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points. RESULTS: Among 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.3%). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, -1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5%; P = 0.048) and beyond 4 weeks (4.7% vs. 11.0%; P = 0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.9%; P<0.001). CONCLUSIONS: In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.).

Robotic versus vaginal radical trachelectomy for reproductive-aged patients with early-stage cervical carcinoma: A multi-center cohort study.

BACKGROUND: A randomized non-inferiority trial showed worse survival in women with early-stage cervical cancer treated with radical hysterectomy by minimally invasive approach compared to laparotomy; the impact of surgical approach on survival following radical trachelectomy is unknown. OBJECTIVE: To examine oncologic outcomes in women with early-stage cervical cancer who underwent robotic or vaginal radical trachelectomy at Canadian cancer centers with the highest volumes of radical trachelectomy procedures. STUDY DESIGN: Retrospective multi-centre cohort analysis which includes patients who had surgery between 2006 and 2019. Women with International FIGO 2009 stage IA-IB cervical cancer who underwent radical trachelectomy and lymph node assessment were grouped by surgical approach (vaginal versus robotic surgery). RESULTS: A total of 197 patients were included from 4 regional referral centres. 56 women underwent robotic radical trachelectomy and 141 underwent vaginal radical trachelectomy. All patients had lymph node assessment by a minimally invasive technique. Median age was 32 years, median tumor size was 12 mm, and median depth of invasion was 5 mm. Recurrence-free survival was 97% in both groups at a median follow-up of 57 months. On multivariable analysis, after adjusting for previously chosen confounders (high risk pathologic criteria, tumor size, and LVSI) there was no statistically significant difference in PFS between the 2 groups (HR 2.1, 95%CI 0.3-7.1, p = 0.5). Tumor size larger than 2 cm (HR 9.4, 95%CI 2.8-26, p = 0.003) was the only variable predictive of recurrence. CONCLUSION: Survival outcomes were excellent in both cohorts of patients undergoing robotic vs. vaginal radical trachelectomy. The surgical approach was not significantly associated with risk of recurrence after adjusting for clinically important confounders.

Hyperviscosity Syndrome Induced Bilateral Visual and Auditory Impairment in Therapy Resistant Waldenström Macroglobulinemia with MYD88 and CXCR4 Mutations.

Hyperviscosity syndrome (HVS) is an emergent complication of Waldenström macroglobulinemia (WM) characterized by visual, neurologic, and rarely auditory impairment. We report a 69-year-old female with MYD88 and CXCR4-mutant WM who developed HVS resulting in bilateral blindness and deafness associated with neurologic manifestations including confusion, severe generalized weakness, and imbalance. Ophthalmologic evaluation revealed bilateral central retinal vein occlusion (CRVO), diffuse retinal hemorrhages, macular edema, and serous macular detachments (SMD). Magnetic resonance imaging of the brain showed bleeding in the inner ears. Management was challenging as her WM was resistant to systemic therapies including bendamustine + rituximab (BR) and rituximab + bortezomib + dexamethasone (RVD). Bruton's tyrosine kinase inhibitors could not be used initially due to ongoing lower gastrointestinal bleeding. She required five total sessions of plasma exchange and was finally initiated on zanubrutinib, achieving a partial response. She also received intravitreal bevacizumab with rapid resolution of the retinal hemorrhages but with little improvement of the SMD. She had partial restoration of her hearing in the right ear and only slight improvement in her bilateral visual deficits. The management of HVS in frail, elderly patients with therapy-resistant WM can be challenging. In these cases, plasma exchange is required until an effective systemic therapy can be safely instituted. Genomic profiling is important in the management of WM as it can predict treatment resistance and guide therapeutic decisions.

Erratum: Closing the gap for cervical cancer research in Vietnam: current perspectives and future opportunities: a report from the 5th Gynecologic Cancer InterGroup (GCIG) Cervical Cancer Research Network (CCRN) Education Symposium.

This corrects the article on p. e88 in vol. 34, PMID: 37668081.

ST-elevation myocardial infarction after thrombolytic therapy with Tenecteplase for acute ischaemic stroke.

Myocardial infarction (MI) secondary to thrombolytic therapy in the setting of acute ischaemic stroke (AIS) is a rare but severe complication. This phenomenon has been well documented in the past with recombinant tissue-type plasminogen activator, also known as Alteplase. However, there are no documented reports of MI secondary to Tenecteplase (TNKase), an alternative thrombolytic agent rapidly gaining favour in managing AIS. We report a male patient in his 50s who received TNKase for an AIS and subsequently developed an inferolateral ST elevation MI.

Circulating adrenal 11-oxygenated androgens are associated with clinical outcome in endometrial cancer.

Context: Recent evidence support that androgens play an important role in the etiology of endometrial cancer (EC). Adrenal-derived 11-oxygenated androgens are highly potent agonists of the androgen receptor (AR), comparable to testosterone (T) and dihydrotestosterone (DHT) that have not been studied in the context of EC. Methodology: We studied a cohort of 272 newly diagnosed postmenopausal EC cases undergoing surgical treatment. Circulating concentrations of seven 11-oxygenated androgens including precursors, potent androgens and their metabolites were established in serum samples collected before and 1 month after surgery using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). Free (unconjugated) and total (free + sulfate and glucuronide conjugates following enzymatic hydrolysis) were analyzed in relation to clinicopathological features, recurrence and disease-free survival (DFS). Results: Levels of 11-oxygenated androgens were weakly correlated to those of canonical androgens such as testosterone (T) and dihydrotestosterone (DHT), with no evidence of their association with clinicopathological features. Levels of 11-oxygenated androgens declined after surgery but remained higher in overweight and obese compared to normal weight cases. Higher levels of preoperative free 11-ketoandrosterone (11KAST) were associated with an increased risk of recurrence (Hazard ratio (HR) of 2.99 (95%CI=1.09-8.18); P=0.03). Postoperative free 11ß-hydroxyandrosterone (11OHAST) levels were adversely associated with recurrence and DFS (HR = 3.23 (1.11-9.40); P=0.03 and 3.27 (1.34-8.00); P=0.009, respectively). Conclusion: 11-oxygenated androgen metabolites emerge as potential prognostic markers of EC.