Compliance to genomic test recommendations to guide adjuvant chemotherapy decision-making in the case of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, in real-life settings.

BACKGROUND: Genomic tests are a useful tool for adjuvant chemotherapy decision-making in the case of hormone receptor-positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-) breast cancer with intermediate prognostic factors. Real-life data on the use of tests can help identify the target population for testing. METHODS: French multicentric study (8 centers) including patients, all candidates for adjuvant chemotherapy for HR-positive, HER2-negative early breast cancer. We describe the percentage of tests performed outside recommendations, according to the year of testing. We calculated a ratio defined as the number of tests required to avoid chemotherapy for one patient, and according to patient and cancer characteristics. We then performed a cost-saving analysis using medical cost data over a period of 1 year from diagnosis, calculated from a previous study. Finally, we calculated the threshold of the ratio (number of tests required to avoid chemotherapy for one patient) below which the use of genomic tests was cost-saving. RESULTS: A total of 2331 patients underwent a Prosigna test. The ratio (performed test/avoided chemotherapy) was 2.8 [95% CI: 2.7-2.9] in the whole population. In the group following recommendations for test indication, the ratio was 2.3 [95% CI: 2.2-2.4]. In the case of non-abidance by recommendations, the ratio was 3 [95% CI: 2.8-3.2]. Chemotherapy was avoided in 841 patients (36%) following the results of the Prosigna test. The direct medical costs saved over 1 year of care were 3,878,798€ and 1,718,472€ in the group of patients following test recommendations. We calculated that the ratio (performed test/avoided chemotherapy) needed to be under 6.9 for testing to prove cost-saving. CONCLUSION: The use of genomic testing proved cost-saving in this large multicentric real-life analysis, even in certain cases when the test was performed outside recommendations.

Psychometric properties of the French Hot Flash Related Daily Interference Scale (HFRDIS).

OBJECTIVE: Hot flashes are one of the major symptoms of climacteric syndrome. Despite the high prevalence of these symptoms, few questionnaires assessing the impact of hot flashes on quality of life have been validated. The aim of this study was to validate a French version of the Hot Flash Related Daily Interference Scale (HFRDIS) in a sample of French women. METHODS: In this prospective study, data were obtained from two groups of women aged between 40 and 60 years from both women without breast cancer and women under hormone therapy for breast cancer between March 2021 and February 2022. Translation was made by an official English-French translator using the forward-backward method. RESULTS: One hundred and sixty-seven women completed the HFRDIS questionnaire. The scree plots confirmed unidimensional structure. Cronbach's α coefficient was 0.92 [0.90-0.94] similar to the original version. The intra-class correlation coefficients of each item ranged between 0.58 and 0.71 Concordance of the scores of each item with those obtained during the validation of the original version of the HFRDIS was confirmed. CONCLUSION: The validation results show that the French version of the HFRDIS questionnaire is a valid tool to evaluate the impact of hot flashes on the daily life activities of patients.

De novo metastatic breast cancer in patients with a small locoregional tumour (T1-T2/N0): Characteristics and prognosis.

INTRODUCTION: The estimated rate of de novo metastatic breast cancer (dnMBC) at the time of diagnosis is between 5 to 12%. International guidelines recommend metastatic work-up (MWU) only in women with advanced breast cancer. The purpose of this study was to describe the characteristics and prognosis of patients with dnMBC diagnosed without an initial indication for MWU. METHODS: We conducted a retrospective, comparative study in dnMBC patients selected from the ESME-MBC cohort. Patients were treated in France between 2008 and 2016. We compared two populations: patients in whom dnMBC was diagnosed by staging although not indicated by guidelines (non-guideline staging [NGS]) and those in whom dnMBC was diagnosed by guideline staging (GS). RESULTS: During the study period, 22,463 patients with MBC were included in the ESME cohort. Among them, 6698 were dnMBC patients. In 247 of these patients (6% of dnMBC and 1% of the overall population), dnMBC was diagnosed by non-guideline staging. Women in this group were significantly younger (57 vs. 59 years, p = 0.02) and had fewer metastatic sites at diagnosis than dnMBC-GS patients. The two groups were not significantly different in terms of the other characteristics. Overall survival (OS) and progression-free survival (PFS) were better in the dnMBC-NGS group than in the dnMBC-GS group. The impact on survival was confirmed by univariate and multivariate analysis (HR 1.83 [1.31-2.57], p < 0.01). CONCLUSION: This study provides the first description of a very specific population. These patients with dnMBC-NGS were younger and more likely to have oligometastatic disease with a better prognosis.

Healthcare-associated infections and antibiotic use in long-term care residents from two geographical regions in Switzerland.

BACKGROUND: The burden of healthcare-associated infections (HAIs) and antimicrobial use in Swiss long-term care facilities (LTCFs) is currently unknown. This study assessed the prevalence of HAIs and antibiotic use among LTCF residents in Switzerland. METHODS: A point-prevalence study was undertaken in LTCFs in eastern and western Switzerland from August to October 2019 according to the 'Healthcare-associated infections in long-term care facilities' (HALT) protocol. Characteristics of residents (age, sex, wounds, dementia, indwelling catheters) and institutions (specific factors, geographic region) were assessed. LTCF residents were screened for HAIs and current antibiotic treatment. Personal and institutional factors associated with HAIs were assessed. RESULTS: In total, 1185 residents from 16 LTCFs (eight per geographic region) were screened for HAIs and antibiotic treatment. Median age was 87 years (interquartile range 79-91) and 71% were female. The prevalence of HAIs was 4.2% (west 4.3% vs east 4.2%; P=0.93), with mucocutaneous skin infections (36%) and respiratory tract infections (30%) being the most common. Independent risk factors for the presence of HAIs were presence of a chronic wound [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.0; P=0.02] and being immobile (OR 1.8, 95% CI 1.0-3.3; P=0.04). Antibiotics were given to 2.9% of residents (west 3.9% vs east 1.8%; P=0.05) on the day of the survey. The most commonly prescribed antibiotics were amoxicillin-clavulanic acid and quinolones. CONCLUSIONS: The prevalence of HAIs in Swiss LTCFs is similar to that in other European countries, whereas antibiotic consumption is lower. Further point-prevalence surveys on a broader scale are recommended to improve understanding of the burden of HAIs and antibiotic consumption in this setting.

HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer.

BACKGROUND: Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC. METHODS: We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR. RESULTS: HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013). CONCLUSION: This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse.

Prosigna test in breast cancer: real-life experience.

PURPOSE: Genomic tests can guide the decision to administer adjuvant chemotherapy in women with hormone receptor (HR)-positive, Human Epidermal growth Factor 2 (HER2)-negative breast cancer (BC) at intermediate risk of recurrence. We assessed the decision-making and economic impact of the Prosigna test in a real-life setting. METHODS: Retrospective cohort study of HR + , HER2- BC patients managed from 2016 to 2020, potential candidates for adjuvant chemotherapy, at intermediate risk of recurrence, in whom a Prosigna test was performed according to contemporary guidelines. The additional cost of chemotherapy over one year in terms of direct medical and non-medical costs was estimated in this study to be €9,737 (derived from a previous study, NCT02813317). The cost of the Prosigna test, as defined by the reimbursement system, was €1,849. RESULTS: Among the 809 patients included in this study, 2.3 Prosigna tests had to be performed to avoid adjuvant chemotherapy for one patient. The number of tests that had to be performed to avoid chemotherapy for one patient was higher for patients with grade 3 tumors and pN1mic axillary node involvement and lower for grade 1 tumors or in the absence of axillary node involvement (pN0), but did not vary according to the 10-year overall survival gain predicted by the Predict online test. The cost saving related to withholding of adjuvant chemotherapy for one patient on the basis of the Prosigna test results was €5,485. CONCLUSION: We present one of the largest cohorts of HR + , HER2- BC patients at intermediate risk of recurrence, in whom a Prosigna test was used to guide the adjuvant therapy decision in a real-life setting, resulting in a 44% decrease in the indication for chemotherapy.

Nosocomial influenza in south-western Swiss hospitals during two seasonal epidemics: an observational study.

BACKGROUND: In Switzerland each year, influenza leads to between 112,000 and 275,000 medical consultations. Data on nosocomial influenza infection are limited. AIM: To describe nosocomial cases of seasonal influenza in south-western Switzerland. METHODS: This study was conducted during two seasonal influenza epidemics from 2016 to 2018 in 27 acute care public hospitals in south-western Switzerland. During these two time-periods, every patient hospitalized for >72 h who was positively screened by reverse transcription-polymerase chain reaction or antigen detection for influenza was included in the survey. Characteristics of patients included age, sex, and comorbidities. Included patients were followed up until discharge or death. Complications and administration of antineuraminidases and/or antibiotics were registered. FINDINGS: The median influenza vaccine coverage of healthcare workers was 40%. In all, 836 patients were included (98% with type A influenza virus in 2016-2017; 77% with type B virus in 2017-2018). Most patients (81%) had an unknown vaccine status. Overall, the incidence of nosocomial influenza was 0.5 per 100 admissions (0.35 per 1000 patient-days). The most frequent comorbidities were diabetes (20%), chronic respiratory diseases (19%), and malnutrition (17%). Fever (77%) and cough (66%) were the most frequent symptoms. Seventy-one percent of patients received antineuraminidases, 28% received antibiotics. Infectious complications such as pneumonia were reported in 9%. Overall, the all-cause mortality was 6%. CONCLUSION: The occurrence of nosocomial influenza underlines the importance of vaccinating patients and healthcare workers, rapidly recognizing community- or hospital-acquired cases, and applying adequate additional measures to prevent dissemination, including the timely administration of antineuraminidases to avoid antibiotic use (and misuse).

Impact of surgical restaging on recurrence in patients with borderline ovarian tumors: A meta-analysis.

OBJECTIVE: The benefits of restaging surgery for patients with a borderline ovarian tumor (BOT) discovered on initial surgery are debatable. We performed a meta-analysis to evaluate the role of restaging surgery on recurrence in patients with BOTs. STUDY DESIGN: We systematically reviewed published studies comparing restaging surgery and incomplete surgery in BOT patients from January 1985 to December 2017. Endpoints were recurrence and mortality rates. Study design features that possibly affected participant selection, reporting of recurrence and death, and manuscript publication were assessed. For pooled estimates of the effect of restaging surgery on recurrence, fixed-effect meta-analytical models were used. RESULTS: Of the 577 articles initially selected, four retrospective observational studies (Restaging group: 166 patients; Non-Restaging group: 394 patients) met our research criteria. No significant differences in terms of recurrence between the two groups were observed (pooled Peto Odds Ratio [OR] = 0.88; 95 % confidence interval [CI]: 0.41-1.92). The number of deaths was insufficient for statistical analysis. CONCLUSIONS: This meta-analysis based on retrospective studies, suggests that restaging surgery does not significantly reduce recurrence in patients with BOT.

Universal screening and decolonization for control of MRSA in nursing homes: follow-up of a cluster randomized controlled trial.

In 2010-11, a trial conducted in nursing homes showed no benefit of meticillin-resistant Staphylococcus aureus (MRSA) universal screening and decolonization over standard precautions to reduce the prevalence of MRSA carriage. Accordingly, no routine screening was performed from 2012. A five-year follow-up shows no new evidence supporting the intervention. Recommendations issued after trial (no screening and decolonization of MRSA residents) were retained.

Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study.

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.

Impact of axillary dissection in women with invasive breast cancer who do not fit the Z0011 ACOSOG trial because of three or more metastatic sentinel lymph nodes.

AIM: The objective of this study was to determine the effects of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy alone (SLNB) on the survival of patients with 3 or more metastatic lymph nodes (MLN) in invasive breast cancer. METHODS: Data of 9521 patients with invasive T1-2M0 breast carcinoma and initial treatment with SLNB completed or not by ALND and 3 or more MLN were extracted from the SEER database. Univariate and multivariate analyses were performed. RESULTS: Overall, 9521 patients were included in the study. SLNB-alone compared with ALND did not result in different overall survival (OS) or specific survival (SS) for patients with 3 or more MLN (p = 0.46 and 0.58, respectively). In subgroup analyses, OS was comparable between SLNB-alone and ALND when patients had only 3 or more than 3 MLN. When patients had 3 MLN, the 5-year SS was significantly better for patients with ALND compared with SLNB-alone: 91.5% and 85.1%, respectively (p = 0.02). The Hazard Ratio (HR) for OS comparing SLNB-alone with ALND adjusting for age, adjuvant radiotherapy, tumor size, estrogen receptor status, grade and tumor type resulted in an HR of 1.05 (95% CI, 0.72-1.54, p = 0.77). CONCLUSION: In conclusion, patients with a T1-T2 invasive breast cancer and at least 3 MLN do not benefit from ALND after SLNB for specific and overall survival, thus limiting ALND to a staging procedure. A subgroup of patients with 3 MLN had a better SS with ALND, possibly due to an under-staging of the SLNB-alone group.

[Locoregional surgery for stage IV breast cancer patients]. / Place du traitement chirurgical locorégional chez les patientes présentant un cancer du sein métastatique d'emblée.

Three to 6% of women newly diagnosed with breast cancers have stage IV disease. Overall survival was improved during the last few years (16-45 months). The treatment of stage IV breast cancer has traditionally been palliative with surgical resection reserved for symptomatic wound complications. Since 2000, several retrospective studies have compared surgery versus no local therapy in women presenting with stage IV breast cancer with an intact primary tumor. All showed a survival advantage for the surgical cohort. However, these studies are limited by the fact that it is not possible to control for biases that led to surgical resection of the primary tumor. Several prospective randomized trials have been undertaken. We have partial results for two of them and they show no survival differences between patients who benefit from local surgery and patients who did not have surgery. However, breast surgery is at low risk of complication, if not considering psychological aspect of mastectomy, and can be proposed to patients with no progression after first chemotherapy. Conservative management can be an option, but surgery must be optimal with negative margins. No benefit of axillary surgery has been shown but this treatment can lead to complications and impact quality of life of patients. Therefore, axillary node resection is not recommended for stage IV breast cancer. Finally, radiotherapy can be an alternative option of local therapy associated or no to surgery in stage IV breast cancer.

[Two- and three-dimensional power Doppler ultrasound in the follow-up of placenta accreta treated conservatively]. / Apport de l'échographique 2D/3D dans le suivi de l'élimination du résidu placentaire après traitement conservateur de placenta accreta.

OBJECTIVES: To determinate the potential of 2D and 3D-ultrasound in the follow-up of patients with placenta accreta treated conservatively. PATIENTS AND METHODS: Seven patients with placenta accreta treated conservatively during June 2007 and September 2009 were included. The follow-up consisted in clinical examination and 2D/3D-ultrasound once a month. Criteria studied included clinical outcome, echogenicity at 2D-ultrasound, vascularisation at colour Doppler, Mean Grey at 3D-ultrasound and vascularisation, flow and perfusion index. RESULTS: Seven women with invasive placenta (3 placentas accreta and 2 percreta) were studied. The mean follow-up was 228 days [75-369]. Mean delay for complete elimination of residual placenta was 280 days [120-365]. The two main results were: presence of an increased anechogenicpart in residual placenta before complete resorption for all patients; a systematic and concomitant stop of genital haemorrhage and vascularisation at colour Doppler. High degrees of variability in parameters measured at 3D-ultrasound were observed between patients so that correlations with clinical outcome were found. CONCLUSION: Long and regular follow-up is essential after conservative management but the role of 3D-ultrasound compared to 2D-ultrasound was not demonstrated in this study.

Evaluation and impact of residual disease in locally advanced cervical cancer after concurrent chemoradiation therapy: results of a multicenter study.

BACKGROUND: The aim of this study was to evaluate the diagnosis and impact of residual disease (RD) after concurrent chemoradiation therapy (CRT) in locally advanced cervical cancer (FIGO IB2-IVA). METHODS: This retrospective multicenter study included 159 patients who were treated with completion surgery after CRT between 2006 and 2012. Magnetic resonance imaging (MRI) was performed 4-6 weeks after CRT and compared to pathological evidence of residual disease. Kaplan-Meier survival curves were plotted and univariate/multivariate analyses were performed to assess the association between RD and the outcome. RESULTS: Residual disease was present in 45.3% of the patients and detected by MRI in 57.1%. The MRI had a 29.2% false positive rate and an 11.1% false negative rate. The overall survival (OS) rates at 3 and 5 years were 78.6% (CI 95% [71%-86.9%]) and 76.5% (CI 95% [68.2%-85.7%]), respectively. The disease free survival (DFS) rates at 3 and 5 years were 73.4% (CI 95% [65.6%-82%]) and 71.1% (CI 95% [62.7%-80.1%]), respectively. RD greater than 10 mm decreased DFS (HR = 4.84, p = 0.03), whereas RD between 1 and 10 mm (HR = 0.31, p = 0.58) and less than 1 mm (HR = 0.37, p = 0.54) had no impact on DFS. The OS was not changed by RD. DISCUSSION: The MRI accuracy value is not sufficient to select patients who might benefit from completion surgery. Residual disease over 10 mm decreased DFS but did not impact OS.

Systematic cavity shaving: modifications of breast cancer management and long-term local recurrence, a multicentre study.

BACKGROUND: The status of the surgical margins of lumpectomy is one of the most important determinants of local recurrence in breast cancer. Systematically practicing cavity margin resection is debated but may avoid surgical re-excision and allow the diagnosis of multifocality. METHODS: This multicentric retrospective study included 294 patients who underwent conservative management of breast cancer with 2-4 systematic cavity shavings. Clinico-biological characteristics of the patients were collected in order to establish whether surgical management was modified by systematic cavity shaving. Local recurrence rate with a long-term follow up of minimum 4 years was evaluated. RESULTS: Cavity shaving avoided the need for re-excision in 25% of cases and helped in the diagnosis of multifocality in 8% of cases. Resection volume was not associated with usefulness of the cavity shaving. No predictive factor of positive cavity shaving was found. The rate of local recurrence was 3.7% and appeared in a median time of 3 years and 8 month. Only one quarter of the patients with local recurrence had initially positive lumpectomy margins but negative cavity shaving. DISCUSSION: Systematic cavity shaving can change surgical management of conservative treatment. No specific target population for useful cavity shaving was found, such that we recommend utilising it systematically.

Genital prolapse repair with Avaulta Plus mesh: functional results and quality of life.

PURPOSE: Evaluate anatomic and functional outcomes of genital prolapse repair by vaginal route using a mixed polypropylene and porcine skin mesh. PATIENTS AND METHODS: Prospective pilot study from January 2009 to January 2011 in the gynecologic department of a tertiary university hospital. Twenty patients with stage II-III genital prolapse underwent anterior wall prolapse repair with anterior Avaulta Plus mesh. Functional results were evaluated using the pelvic floor distress inventory-short form (PFDI-20), the pelvic floor impact questionnaire-7 (PFIQ-7) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual questionnaires (PISQ-12). RESULTS: No per-operative complications occurred. One postoperative hematoma (5%) occurred requiring a second surgery. At a mean follow-up of 19.7 months, three patients had vaginal mesh exposure (15%) requiring a second surgery for two of them. Of the 20 women, 17 (85%) had optimal anatomic results and three (15%) had residual genital prolapse (Ba=-2 in two cases and Bp = -2 in the one). No recurrence was observed during the study period. A significant improvement in the PFDI-20 (P<0.001) and PFIQ-7 scores (P<0.001) was observed but no improvement in the PISQ-12 score. CONCLUSION: In this series, we reported that genital prolapse repair using Avaulta Plus mesh resulted in a high success rate and improved quality of life but with an important prevalence of vaginal mesh exposure.