Maximal-effort cytoreductive surgery for ovarian cancer patients with a high tumor burden: variations in practice and impact on outcome

Background This study aimed to compare the outcomes of two distinct patient populations treated within two neighboring UK cancer centers (A and B) for advanced epithelial ovarian cancer (EOC). Methods A retrospective analysis of all new stages 3 and 4 EOC patients treated between January 2013 and December 2014 was performed. The Mayo Clinic surgical complexity score (SCS) was applied. Cox regression analysis identified the impact of treatment methods on survival. Results The study identified 249 patients (127 at center A and 122 in centre B) without significant differences in International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO 4, 29.7% at centers A and B), Eastern Cooperative Oncology Group (ECOG) performance status (ECOG < 2, 89.9% at centers A and B), or histology (serous type in 84.1% at centers A and B). The patients at center A were more likely to undergo surgery (87% vs 59.8%; p < 0.001). The types of chemotherapy and the patients receiving palliative treatment alone were equivalent between the two centers (3.6%). The median SCS was significantly higher at center A (9 vs 2; p < 0.001) with greater tumor burden (9 vs 6 abdominal fields involved; p < 0.001), longer median operation times (285 vs 155 min; p < 0.001), and longer hospital stays (9 vs 6 days; p < 0.001), but surgical morbidity and mortality were equivalent. The independent predictors of reduced overall survival (OS) were non-serous histology (hazard ratio [HR], 1.6; 95% confidence interval [CI] 1.04–2.61), ECOG higher than 2 (HR, 1.9; 95% CI 1.15–3.13), and palliation alone (HR, 3.43; 95% CI 1.51–7.81). Cytoreduction, of any timing, had an independent protective impact on OS compared with chemotherapy alone (HR, 0.31 for interval surgery and 0.39 for primary surgery), even after adjustment for other prognostic factors. Conclusions Incorporating surgery into the initial EOC management, even for those patients with a greater tumor burden and more disseminated disease, may require more complex procedures and more resources in terms of theater time and hospital stay, but seems to be associated with a significant prolongation of the patients overall survival compared with chemotherapy alone. Maximal-effort cytoreductive surgery aimed at total macroscopic tumor clearance combined with platinum-based chemotherapy and targeted agents is the cornerstone of modern primary epithelial ovarian cancer (EOC) management.1 Although findings have shown high tumor burden to be associated with a less favorable overall outcome than more advantageous tumor dissemination patterns with less disease,2 multiple prospective and retrospective series have long demonstrated a strong positive association between total macroscopic tumor clearance rates and survival, not only on an individual basis but also at the level of large patient cohorts, in which individual tumor biology-related factors are less likely to skew collective survival data.1,3, 4, 5, 6, 7, 8 The team of Chi et al. recently presented the survival data for all advanced EOC patients treated at Memorial Sloan Kettering categorized by year of primary debulking surgery based on the implementation of surgical changes in their approach to ovarian cancer debulking. Their study demonstrated that complete gross resection rates, progression-free survival (PFS) and overall survival (OS) increased during the 13-year evaluation period despite operating on higher-stage disease and patients with a greater tumor burden. This was assumed to be largely attributable to the surgical paradigm shifts implemented specifically to achieve more complete surgical cytoreduction, even for patients with a less favorable disease profile.4 Nevertheless, as with all medical and surgical advances, their broader implementation varies greatly nationally and internationally, not just due to differences in the available resources, but also because of long-established local practice and broad disparities in overall philosophy as well as in individual and infrastructural expertise.3,6,8,9 Especially for patients with a high tumor burden, in which therapeutic effort often is challenged, not only by the disease itself but also by the impact that this advanced disease has on the actual patient, both personal and infrastructural resources and expertise often are stretched, and hence reasonable doubt arises about the limitations and limits of optimal treatment.2,3,6 The current analysis aimed to demonstrate how differences in local practice may influence the patient’s outcome by evaluating not only the surgical patients, but also the entire EOC cohort treated at one of two large UK cancer centers in an attempt to exclude a selection bias of seemingly more favorable and operable patients7,10,11 and have all ovarian cancer patients in the denominator, including those women with more adverse tumor profiles and higher tumor load

Clinical and Survival differences during separate COVID-19 surges: investigating the impact of the Sars-CoV-2 alpha variant in critical care patients

A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p<0.05) and d-dimer lower. The 28-day mortality was not statistically significant (1st wave: 42.2% vs 2nd wave: 39.8%). However, when adjusted for key covariates, the hazard ratio for 28-day mortality in those patients with B.1.1.7 was 3.79 (CI 1.04–13.8; p=0.043) compared to the original strain. During the second surge in the UK, where the COVID-19 variant B.1.1.7 was most prevalent, significantly more patients presented to critical care with severe ARDS. Furthermore, mortality risk was significantly greater in our ICU population during the second wave of the pandemic in those patients with B.1.1.7. As ICUs are experiencing further waves (particularly by the delta (B.1.617.2) variant), we highlight the urgent need for prospective studies describing immunological and pathophysiological differences across novel emerging variants