18F]FDG PET/CT Imaging for Predicting Outcomes in Breast Cance

International audienceBackground: [18F]FDG PET/CT is used for staging and could also provide information associated with clinical outcomes. The objective of this study was to determine the clinical utility of biomarkers measured using [18F]FDG PET/CT to predict the absence of pathological complete response (no-pCR) and recurrence. Methods: In this retrospective study, we included patients with non-special-type breast carcinoma who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy between 2011 and 2019. Clinicopathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from PET images. The association between biomarkers and no-pCR was studied using logistic regression. The cut-off value was determined using the area under the ROC Curve. To predict 3-year recurrence-free survival (RFS), we used a multivariable Cox model, and the cut-off value was determined using time-dependent ROC and predictiveness curves. Results: Two hundred and eighty-six patients were included in the analysis. One hundred and twelve patients had a pCR (39.2%). The pCR rate was significantly higher in patients with a high nuclear grade (p 9.0 cm3) was significantly associated with no-pCR in the whole cohort (OR = 2.4, 95% CI: 1.3–4.2, p 13.5 cm3) was associated with shorter RFS (HR = 4.0, 95% CI: 1.9–8.4, p < 0.01). Conclusion: High TMTV in pre-therapeutic imaging is associated with no-pCR and recurrence. It can help in identifying high-risk patients and be considered as an intensified or alternative adjuvant therapy for closely monitoring patients

A DNA methylation-based liquid biopsy for triple-negative breast cancer

Abstract Here, we present a next-generation sequencing (NGS) methylation-based blood test called methylation DETEction of Circulating Tumour DNA (mDETECT) designed for the optimal detection and monitoring of metastatic triple-negative breast cancer (TNBC). Based on a highly multiplexed targeted sequencing approach, this assay incorporates features that offer superior performance and included 53 amplicons from 47 regions. Analysis of a previously characterised cohort of women with metastatic TNBC with limited quantities of plasma (<2 ml) produced an AUC of 0.92 for detection of a tumour with a sensitivity of 76% for a specificity of 100%. mDETECTTNBC was quantitative and showed superior performance to an NGS TP53 mutation-based test carried out on the same patients and to the conventional CA15-3 biomarker. mDETECT also functioned well in serum samples from metastatic TNBC patients where it produced an AUC of 0.97 for detection of a tumour with a sensitivity of 93% for a specificity of 100%. An assay for BRCA1 promoter methylation was also incorporated into the mDETECT assay and functioned well but its clinical significance is currently unclear. Clonal Hematopoiesis of Indeterminate Potential was investigated as a source of background in control subjects but was not seen to be significant, though a link to adiposity may be relevant. The mDETECTTNBC assay is a liquid biopsy able to quantitatively detect all TNBC cancers and has the potential to improve the management of patients with this disease

Time to Pregnancy, Obstetrical and Neonatal Outcomes after Breast Cancer: A Study from the Maternity Network for Young Breast Cancer Patients

Although an increasing number of young breast cancer (BC) patients have a pregnancy desire after BC, the time necessary to obtain a pregnancy after treatment and subsequent outcomes remain unknown. We aimed to determine the time to evolutive pregnancy in a cohort of BC survivors and subsequent obstetrical and neonatal outcomes. We analyzed BC patients treated at Institut Curie from 2005–2017, aged 18–43 years old (y.o.) at diagnosis having at least one subsequent pregnancy. 133 patients were included, representing 197 pregnancies. Mean age at BC diagnosis was 32.8 y.o. and at pregnancy beginning was 36.8 y.o. 71% pregnancies were planned, 18% unplanned and 86% spontaneous. 64% pregnancies resulted in live birth (n = 131). Median time from BC diagnosis to pregnancy beginning was 48 months and was significantly associated with endocrine therapy (p &lt; 0.001). Median time to pregnancy was 4.3 months. Median time to evolutive pregnancy 5.6 months. In multivariate analysis, menstrual cycles before pregnancy remained significantly associated with time to pregnancy and endocrine therapy with time evolutive to pregnancy. None of the BC treatments (chemotherapy/endocrine therapy/trastuzumab) was significantly associated with obstetrical nor neonatal outcomes, that seemed comparable to global population. Our findings provide reassuring data for pregnancy counseling both in terms of delay and outcome

Sequencing and titrating approach of therapy in heart failure with reduced ejection fraction following the 2021 European Society of Cardiology guidelines: an international cardiology survey

AIMS: In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists. METHODS AND RESULTS: An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32-47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), beta-blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose cotransporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers. CONCLUSION: In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices

Sequencing and Titrating Approach of Therapy in Heart Failure with Reduced Ejection Fraction Following the 2021 ESC guidelines: an International Cardiology Survey

International audienceThe latest European guidelines for heart failure with reduced ejection fraction (HFrEF) patients recommend initiating four major therapeutic classes rather than the sequential initiation from the previous guidelines. Without any evidence from randomized controlled trials, the perception and the practical approach to these guidelines by practicing cardiologists remain unclear. We found that left ventricular ejection fraction (LVEF) ≤40% remains the most frequent threshold to define HFrEF and the ‘historical’ approach to HFrEF drug titration remains the most popular sequencing approach. However, most participants felt that starting all four classes was feasible within the initial hospitalization and that titration is less important than introducing a new class. This is the first and largest survey providing real-world data on HFrEF drug introduction and titration after the latest European heart failure guidelines. Even if the ‘historical’ sequencing approach remains dominant, starting all four classes in a short-time period was perceived as feasible. Strategy trials in treatment guidance are now needed to demonstrate the safety and define the best treatment implementation approac

COVID-19 in breast cancer patients: A cohort at the Institut Curie hospitals in the Paris area

International audienceBackground: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods: An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. Results: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients

30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.

BACKGROUND There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates. METHODS We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020. RESULTS Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country. CONCLUSIONS BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak

Effect of BMI on safety of bariatric surgery during the COVID-19 pandemic, procedure choice, and safety protocols - An analysis from the GENEVA Study

Background: It has been suggested that patients with a Body Mass Index (BMI) of &gt; 60 kg/m2 should be offered expedited Bariatric Surgery (BS) during the Coronavirus Disease-2019 (COVID-19) pandemic. The main objective of this study was to assess the safety of this approach. Methods: We conducted a global study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into three groups according to their preoperative BMI -Group I (BMI &lt; 50 kg/m2), Group II (BMI 50-60 kg/m2), and Group III (BMI &gt; 60 kg/m2). The effect of preoperative BMI on 30-day morbidity and mortality, procedure choice, COVID-19 specific safety protocols, and comorbidities was assessed. Results: This study included 7084 patients (5197;73.4 % females). The mean preoperative weight and BMI were 119.49 &amp; PLUSMN; 24.4 Kgs and 43.03 &amp; PLUSMN; 6.9 Kg/m2, respectively. Group I included 6024 (85 %) patients, whereas Groups II and III included 905 (13 %) and 155 (2 %) patients, respectively.The 30-day mortality rate was higher in Group III (p = 0.001). The complication rate and COVID-19 infection were not different. Comorbidities were significantly more likely in Group III (p = &lt; 0.001). A significantly higher proportion of patients in group III received Sleeve Gastrectomy or One Anastomosis Gastric Bypass compared to other groups. Patients with a BMI of &gt; 70 kg/m2 had a 30-day mortality of 7.7 % (2/26). None of these patients underwent a Roux-en-Y Gastric Bypass. Conclusion: The 30-day mortality rate was significantly higher in patients with BMI &gt; 60 kg/m2. There was, however, no significant difference in complications rates in different BMI groups, probably due to differences in procedure selection

Safety of Bariatric Surgery in ≥ 65-Year-Old Patients During the COVID-19 Pandemic

Background Age &gt;= 65 years is regarded as a relative contraindication for bariatric surgery. Advanced age is also a recognised risk factor for adverse outcomes with Coronavirus Disease-2019 (COVID-19) which continues to wreak havoc on global populations. This study aimed to assess the safety of bariatric surgery (BS) in this particular age group during the COVID-19 pandemic in comparison with the younger cohort.Methods We conducted a prospective international study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into two groups - patients &gt;= 65-years-old (Group I) and patients &lt; 65-years-old (Group II). The two groups were compared for 30-day morbidity and mortality.Results There were 149 patients in Group 1 and 6923 patients in Group II. The mean age, preoperative weight, and BMI were 67.6 +/- 2.5 years, 119.5 +/- 24.5 kg, and 43 +/- 7 in Group I and 39.8 +/- 11.3 years, 117.7 +/- 20.4 kg, and 43.7 +/- 7 in Group II, respectively. Approximately, 95% of patients in Group 1 had at least one co-morbidity compared to 68% of patients in Group 2 (p = &lt; 0.001). The 30-day morbidity was significantly higher in Group I ( 11.4%) compared to Group II (6.6%) (p = 0.022). However, the 30-day mortality and COVID-19 infection rates were not significantly different between the two groups.Conclusions Bariatric surgery during the COVID-19 pandemic is associated with a higher complication rate in those &gt;= 65 years of age compared to those &lt; 65 years old. However, the mortality and postoperative COVID-19 infection rates are not significantly different between the two groups

30-Day morbidity and mortality of bariatric metabolic surgery in adolescence during the COVID-19 pandemic – The GENEVA study

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n&nbsp;=&nbsp;122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7&nbsp;± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n&nbsp;=&nbsp;146; 85.9%), only 42.4% (n&nbsp;=&nbsp;72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n&nbsp;=&nbsp;9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients