Information needs on nutrition in link to cancer prevention among cancer patients, high-risk individuals and general population - A national cross-sectional study.

BACKGROUND & AIMS: Nutrition is one of the fundamentals of cancer prevention. Knowing what are the patients' needs and beliefs in terms of "nutrition and cancer" information helps tailor future nutritional interventions. The aim of this study was to evaluate specific information needs about "nutrition in relation to cancer prevention", including primary and tertiary prevention, among cancer patients, cancer-free individuals, and genetic high cancer risk individuals. METHODS: This online survey was shared within two large National cancer social networks and proposed to all attendees and carers of a comprehensive cancer center. RESULTS: 2887 individuals answered the survey (of whom 33% were cancer patients, 13% high-risk individuals and 55% participants of the general population). More than 80% of participants were women, had at least a high school degree. Median body mass index was 23.2 kg/m2. Eleven percent (n = 321) were following a diet, mostly low carbohydrate and weight-loss diets. Around 70% of all categories felt they lacked information on nutrition and cancer interplays. Only 12% of cancer patients (n = 108) considered they had received enough information on nutrition during their care pathway. A majority of participants agreed that food can modify cancer risk (93%, n = 2526) and 66% (n = 1781) considered that nutrition should be personalized according to the risk of cancer. Only twenty-nine percent (n = 792) believed that eating 5 fruits and vegetables a day was enough to avoid cancer, but 64% (n = 1720) thought that dietary supplements could help obtain a better health. All proposed nutrition topics were considered important by the participants. CONCLUSIONS: Although cancer patients and cancer-free respondents, whether at high risk of cancer or not, share a common broad interest on the interplay between nutrition and cancer and seek after more information on this topic, some false beliefs are observed. Healthcare providers could successfully propose more evidence-based information to these populations.

Clinical utility of circulating tumor DNA sequencing with a large panel: a National Center for Precision Medicine (PRISM) study.

BACKGROUND: Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors. PATIENTS AND METHODS: Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible. RESULTS: Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively. CONCLUSIONS: ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies.

The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients.

Germline DNA alterations affecting homologous recombination pathway genes have been associated with pancreatic cancer (PC) risk. BRCA2 is the most studied gene and affects the management of PC patients and their families. Even though recent reports have suggested a similar role of germline ATM pathogenic variants (PV) in familial PC, there is still a disagreement between experts on how it could affect patient management given the lack of proper PC risk estimates. We retrospectively analyzed the germline data of 257 PC patients among whom nearly 50% were sporadic cases. We showed similar frequencies of BRCA2 (4.9%) and ATM (4.4%) PV or likely pathogenic variants, which were not related to familial history. Based on our findings and that of the literature, we suggest including ATM gene among the panel of genes analyzed in PC patients pending the publication of prospective studies.

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9 years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27 months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.

[Recommendations for genetic testing and management of individuals genetically at-risk of cutaneous melanoma]. / Recommandations pour le diagnostic de prédisposition génétique au mélanome cutané et pour la prise en charge des personnes à risque.

Cutaneous melanoma is a multifactorial disease resulting from both environmental and genetic factors. Five susceptibility genes have been identified over the past years, comprising high-risk susceptibility genes (CDKN2A, CDK4, and BAP1 genes) and intermediate-risk susceptibility genes (MITF, and MC1R genes). The aim of this expert consensus was to define clinical contexts justifying genetic analyses, to describe the conduct of these analyses, and to propose surveillance recommendations. Given the regulatory constraints, it is recommended that dermatologists work in tandem with a geneticist. Genetic analysis may be prescribed when at least two episodes of histologically proven invasive cutaneous melanoma have been diagnosed before the age of 75 years in two 1st or 2nd degree relatives or in the same individual. The occurrence in the same individual or in a relative of invasive cutaneous melanoma with ocular melanoma, pancreatic cancer, renal cancer, mesothelioma or a central nervous system tumour are also indications for genetic testing. Management is based upon properly managed photoprotection and dermatological monitoring according to genetic status. Finally, depending on the mutated gene and the familial history, associated tumour risks require specific management (e.g. ocular melanoma, pancreatic cancer). Due to the rapid progress in genetics, these recommendations will need to be updated regularly.

Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium "Care for CMMR-D" (C4CMMR-D).

Lynch syndrome (LS) is an autosomal dominant disorder caused by a defect in one of the DNA mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. In the last 15 years, an increasing number of patients have been described with biallelic mismatch repair gene mutations causing a syndrome referred to as 'constitutional mismatch repair-deficiency' (CMMR-D). The spectrum of cancers observed in this syndrome differs from that found in LS, as about half develop brain tumours, around half develop digestive tract cancers and a third develop haematological malignancies. Brain tumours and haematological malignancies are mainly diagnosed in the first decade of life, and colorectal cancer (CRC) and small bowel cancer in the second and third decades of life. Surveillance for CRC in patients with LS is very effective. Therefore, an important question is whether surveillance for the most common CMMR-D-associated cancers will also be effective. Recently, a new European consortium was established with the aim of improving care for patients with CMMR-D. At a workshop of this group held in Paris in June 2013, one of the issues addressed was the development of surveillance guidelines. In 1968, criteria were proposed by WHO that should be met prior to the implementation of screening programmes. These criteria were used to assess surveillance in CMMR-D. The evaluation showed that surveillance for CRC is the only part of the programme that largely complies with the WHO criteria. The values of all other suggested screening protocols are unknown. In particular, it is questionable whether surveillance for haematological malignancies improves the already favourable outcome for patients with these tumours. Based on the available knowledge and the discussions at the workshop, the European consortium proposed a surveillance protocol. Prospective collection of all results of the surveillance is needed to evaluate the effectiveness of the programme.

Should BRCA2 mutation carriers avoid neoadjuvant chemotherapy?

BRCA2 mutation carriers typically develop luminal B breast cancers. Data on the effectiveness of neoadjuvant chemotherapy in these patients are limited because of small patient numbers and lack of prospective studies. We used our 15-year genetic clinic database to compare retrospectively the pathological complete response rates (pCR) and rates of post-chemotherapy nodal involvement among BRCA2 carriers and BRCA1/2-negative (WT) patients with luminal B tumours, all treated with neoadjuvant anthracyclines±taxanes-based chemotherapy. Twenty-nine BRCA2 carriers and 67 WT patients fulfilled the inclusion criteria and were analysed. Patients and treatment characteristics were represented. A pCR occurred in 3 (10%) BRCA2 patients and 13 (19%) WT patients (p=0.43). Twenty (69%) BRCA2 carriers and 34 (51%) WT patients remained node-positive at surgery (p=0.17). BRCA2 germline mutations are associated with a low probability of pCR and a high risk of axillary invasion. Alternative treatments are highly expected, and clinical trials are needed to set the best treatment regimen in this population.

Short-term psychological impact of the BRCA1/2 test result in women with breast cancer according to their perceived probability of genetic predisposition to cancer.

BACKGROUND: The effect of BRCA1/2 gene test result on anxiety, depression, cancer-related thought intrusion or avoidance and perceived control over cancer risk was assessed in breast cancer (BC) patients, according to their perceived probability of genetic predisposition to cancer. METHODS: Two hundred and forty-three (89% response rate) women with BC completed questionnaires after an initial genetic counselling visit (T1), of which 180 (66%) completed questionnaires again after receiving the BRCA1/2 results (T2). The discrepancy between women's perceived probability of cancer genetic predisposition at T1 and the geneticist's computed estimates was assessed. RESULTS: In all, 74% of women received a negative uninformative (NU), 11% a positive BRCA1/2 and 15% an unclassified variant (UV) result. On hierarchical regression analysis, in women with a positive BRCA1/2 result (vs NU or UV), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted lower levels of anxiety at T2 (ß=-0.28; P<0.01), whereas in women receiving a UV result (vs NU or positive BRCA1/2), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted higher levels of anxiety (ß=0.20; P<0.01), depression (ß=0.19; P<0.05) and intrusion (ß=0.18; P<0.05) at T2. CONCLUSION: The type of BRCA1/2 test result differently affects distress according to women's perceived probability of genetic predisposition before testing.

French women's breast self-examination practices with time after undergoing BRCA1/2 genetic testing.

To assess the impact of BRCA1/2 genetic test results on cancer-free women's breast-self-examination (BSE) practices and to prospectively determine their influence on psychological functioning. A prospective longitudinal study on French women's BSE practices and frequencies in BRCA1/2 carriers (N = 217) and non-carriers (N = 313) 1 and 2 years following disclosure of the test results, along with psychological factors predicting BSE practices. Before disclosure, BSE was practised by 47.2% of the women, and increased to 57.3% 1 year later. No change in the women's practices was noted between 12 and 24 months after the test. Carriers and non-carriers practicing regularly BSE at baseline were, respectively 8 to 6 times more likely to be practising BSE regularly at 12 months after being tested. Among the carriers, having fewer depressive symptoms at baseline and believing in the ability of BSE to detect breast cancer were found to be the most decisive factors associated with BSE practices 1 year after disclosure, following adjustment for BSE baseline practices. Among the non-carriers, believing in the ability of BSE to detect breast cancer, greater post-test anxiety, and a higher perceived risk of breast cancer were found to be predictors of post-test BSE practices after adjusting for BSE baseline practices. In France, where performing BSE is neither mandatory nor recommended, an increase in BSE practices was found to occur after disclosure of women's genetic test results, regardless of their carrier status.

Effects of the removal of vision on body sway during different postures in elite gymnasts.

The aim of this study was to analyse the effects of the removal of vision on postural performance and postural control in function of the difficulty and specificity of the posture. Twelve elite gymnasts were instructed to be as stable as possible with eyes open and eyes closed in three postures: bipedal, unipedal, and handstand ranked from the less difficult and less specific to the more difficult and more specific. The ratios eyes closed on eyes open, computed on CP surface and CP mean velocity, which respectively represents postural performance and postural control, were similar in the bipedal and handstand postures. They were highly increased in the unipedal one. The effect of the removal of vision and so the role of vision on body sway was not directly linked to the difficulty or specificity of the posture; other tasks' characteristics like the segments configuration also played a role.

Quality end-of-life care in long-term care facilities: service providers' perspective.

The goal of this project was to provide guidance on what constitutes quality end-of-life care in long-term care (LTC) facilities. Seventy-nine direct care providers from six LTC facilities participated in 12 focus groups. The focus group discussions examined what made the difference between a "good" death and a "bad" death, and what changes in LTC would improve the care of dying residents. Analyses of the focus group data revealed six themes that contribute to quality end-of-life care in LTC facilities: responding to resident needs, creating a homelike environment, supports for families, providing quality care processes, recognizing death as a significant event, and having sufficient institutional resources. These findings challenge policy makers and providers to consider how to normalize life and death in LTC facilities.

Is there a transfer of postural ability from specific to unspecific postures in elite gymnasts?

The purpose of this study was to investigate the transfer of postural ability by comparing the level of performance and postural control of elite gymnasts in postures specifically trained or not. Fifteen elite gymnasts were asked to stand as still as possible with eyes opened in three conditions: bipedal, unipedal and handstand. Surface and mean velocity of the centre of pressure motions were used to quantify respectively performance and postural control. A ranking was made for each parameter to determine the level of each subject. As a whole, the subject's level of postural performance and control in one condition was not correlated to the corresponded level in another condition. Therefore, postural ability of elite gymnasts in the handstand is not transferable to upright standing postures.

Center of gravity motions and ankle joint stiffness control in upright undisturbed stance modeled through a fractional Brownian motion framework.

The authors modeled the center of gravity vertical projection (CG(v)) and the difference, CP - CG(v), which, combined, constitute the center of pressure (CP) trajectory, as fractional Brownian motion in order to investigate their relative contributions and their spatiotemporal articulation. The results demonstrated that CG(v) and CP - CG(v) motions are both endowed in complementary fashion with strong stochastic and part-deterministic behaviors. In addition, if the temporal coordinates remain similar for all 3 trajectories by definition, the switch between the successive control mechanisms appears for shorter displacements for CP - CG(v) and CG(v) than for CP trajectories. Results deduced from both input (CG(v)) and muscular stiffness (CP - CG(v)) thus provide insight into the way the central nervous system regulates stance control and in particular how CG and CP - CG are controlled.

A comparative analysis of the center of gravity and center of pressure trajectory path lengths in standing posture: an estimation of active stiffness.

The center of foot pressure (CP) motions, representing the net neuromuscular control, was compared to the center of gravity (CG) motions, representing the net performance. The comparison focused on the trajectory path length parameter along the medio-lateral and antero-posterior axes because these two variables depend on amplitude versus frequency relationship. This relationship was used to evaluate the CG motions based on the CP motions. Seven subjects stood still on a force plate with eyes open and eyes closed. The results showed that the ratio of (CP-CG)/CP trajectory path length was personal for each subject. These results suggest different levels of passive (ligaments, elastic properties) and active (reflex activity) stiffness. For some subjects, this ratio was significantly lower for the eyes open condition than for the eyes closed condition, indicating a decrease of the active stiffness for the eyes open condition. Therefore, a CG-CP comparative analysis appeared helpful in understanding the control of balance and necessary to quantify the subjects' net performance.