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Background: The longitudinal hospital care experiences of older adults with cancer, from the treatment decision-making process until their end of life, remain unexplored. We examined the hospital care trajectories of these patients and identified associated clinical determinants., Materials and Methods: We linked the ELCAPA multicenter cohort study (patients aged ≥70 with a solid tumor and having been referred for a geriatric assessment between 2012 and 2019) and the Greater Paris University Hospitals' clinical data warehouse. Individual care trajectories, defined as series of consultations, hospital admissions (in day, acute, or rehabilitation units), and emergency room (ER) visits, were clustered using multichannel sequence analysis. Cluster membership determinants were identified among socio-demographic, oncological, and geriatric parameters by logistic regression analysis., Results: Seven hundred seven patients (median age: 82; metastatic cancer: 45.2%; 10 998 care episodes) were included. Four trajectory clusters were identified: cluster A (n = 149, 21.1%) with in-hospital surgical trajectories, cluster B (n = 198, 28.0%) with outpatient care trajectories with chemotherapy and/or radiotherapy, cluster C (n = 302, 42.7%) without any hospital cancer treatments, and cluster D (n = 58, 8.2%) with mostly chemotherapy and high hospital care consumption. Cluster belonging determinants included metastatic status and cancer site (for cluster A); cognition, mobility, and mood status (unimpaired parameters for cluster B and impaired for cluster C); and younger age (for cluster D)., Conclusions: While highlighting varied hospital care experiences among older patients with cancer, we found that age remains an independent determinant of chemotherapy-dominant care trajectories., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Automated frailty screening tools like the Hospital Frailty Risk Score (HFRS) are primarily validated for care consumption outcomes. We assessed the predictive ability of the HFRS regarding care consumption outcomes, frailty domain impairments and mortality among older adults with cancer, using the Geriatric 8 (G8) screening tool as a clinical benchmark., Methods: This retrospective, linkage-based study included patients aged ≥70 years with solid tumor, enrolled in the Elderly Cancer Patients (ELCAPA) multicentre cohort study (2016-2020) and hospitalized in acute care within the Greater Paris University Hospitals. HFRS scores, which encompass hospital-acquired problems and frailty-related syndromes, were calculated using data from the index admission and the preceding 6 months. A multidomain geriatric assessment (GA), including cognition, nutrition, mood, functional status, mobility, comorbidities, polypharmacy, incontinence, and social environment, was conducted at ELCAPA inclusion, with computation of the G8 score. Logistic and Cox regressions measured associations between the G8, HFRS, altered GA domains, length of stay exceeding 10 days, 30-day readmission, and mortality., Results: Among 587 patients included (median age 82 years, metastatic cancer 47.0%), 237 (40.4%) were at increased frailty risk by the HFRS (HFRS>5) and 261 (47.5%) by the G8 (G8≤10). Both HFRS and G8 were significantly associated with cognitive and functional impairments, incontinence, comorbidities, prolonged length of stay, and 30-day mortality. The G8 was associated with polypharmacy, nutritional and mood impairment., Discussion: Although showing significant associations with short-term care consumption, the HFRS could not identify polypharmacy, nutritional, mood and social environment impairments and showed low discriminatory ability across all GA domains., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs)., Objective: We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma., Patients and Methods: We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946)., Results: The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5-58.6), with marked between-study heterogeneity (I 2  = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule., Conclusions: This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin-2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio-target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma., Methods and Results: Methods and results: We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial-to-mesenchymal transition (EMT) marker expression and ferroptosis resistance. This was also found in renal cell carcinoma and triple negative breast cancer patient-derived xenograft models. Using an oligonucleotide anti-sense anti-PROM2, we efficaciously decreased PROM2 expression and prevented metastases in melanoma xenografts. We also demonstrated that PROM2 was implicated in an aggravation loop, contributing to increase the metastatic burden both in murine metastatic models and in patients with metastatic melanoma. The metastatic burden is closely linked to PROM2 expression through the expression of EMT markers and ferroptosis cell death resistance in a deterioration loop., Conclusion: Our results open the way for further studies using PROM2 as a bio-target in resort situations in human metastatic melanoma and also in other cancer types., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Cutaneous squamous cell carcinomas in kidney-transplant recipients are frequent, with an increasing incidence linked to long immunosuppression durations and exposure to ultraviolet radiation. p53 is at the cornerstone of ultraviolet-induced DNA damage, but the role of p53 post-translational modifications in this context is not yet deciphered. Here, we investigated the phosphorylation status of p53 at Serine 392 in 25 cutaneous squamous cell carcinomas in kidney-transplant recipients, compared with 22 non-transplanted patients. Cutaneous squamous cell carcinomas in transplanted patients occurred after a median period of 19 years of immunosuppression, with a median number of 15 cutaneous squamous cell carcinomas and more aggressive histological and clinical characteristics. There was no significant difference between Ki67, p53, and pSer392p53 expression in the two groups. Using principal component analysis, we identified a cluster of exclusively transplanted patients with a median of 23 years of immunosuppression duration, significantly more aggressive biological characteristics, and higher pSer392p53 expression. pSer392p53 was expressed in the whole tumor, suggesting an early carcinogenic event in the course of prolonged immunosuppression. This high, diffuse pSer392p53 expression, corresponding to a high level of DNA damage, might be useful to identify aggressive cutaneous squamous cell carcinomas in kidney-transplant recipients to treat them more aggressively.

Background: To compare safety and efficacy of ICIs among patients<80 and those ≥80 years of age., Methods: A single-center retrospective observational cohort study comparing patients<80 and ≥80 years of age matched for cancer site (lung vs others) and participation in a clinical trial., Primary Endpoint: grade ≥2 toxicity during the first three months of ICI therapy. The two groups were compared using univariate and multivariate regression., Results: Two hundred and ten consecutive patients were recruited, with the following characteristics: mean age: 66.5±16.8, 20% aged ≥80 years, 75% male, 97% ECOG-PS ≤ 2, 78% G8-index ≤ 14/17, 80% lung or kidney cancer, and 97% metastatic cancer. The grade ≥2 toxicity rate during the first three months of ICI therapy was 68%. Patients aged ≥80 years of age had a more significant (P<0.05) proportion of grade ≥2 non-hematological toxicities (64% vs 45%) than those aged<80 years: rash (14% vs 4%), arthralgia (7.1% vs 0.6%), colitis (4.7% vs 0.6%), cytolysis (7.1% vs 1.2%), gastrointestinal bleeding (2.4% vs 0%), onycholysis (2.4% vs 0%), oral mucositis (2.4% vs 0%), psoriasis (2.4% vs 0%), or other skin toxicities (25% vs 3%). Efficacy among patients ≥80 and<80 years of age was comparable., Conclusions: Although non-hematological toxicities affected 20% more patients aged ≥80 years, hematological toxicities and efficacy were comparable between patients aged ≥80 and<80 years with advanced cancer and treated with ICIs., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Few studies compared both ultrasound and histological approaches for the same series of patients with chronic venous disease (CVD). We aimed to assess the diagnostic performances of duplex ultrasound assessment (US) of Vein Wall Thickness (VWT) among patients with CVD., Methods: 38 adults with primary varicose veins having undergone Great Saphenous Vein thermal ablation with phlebectomy, and agreeing to biopsy of the Posterior Accessory Great Saphenous Vein (PASV) were consecutively included in a two-center prospective study. VWT assessment of the PASV was performed using both US, and microscope examination. High values for microscope-assessed VWT were defined at > 0.5 mm., Results: The mean age was 53.0 ± 13.1 years, 71% were women. Maximization of US performances was obtained with a threshold of 0.6 mm: Sensitivity (Se) = 92.9%, Specificity (Sp) = 91.7%, positive (86.7%) and negative predictive value (NPV) (95.7%), positive (11.1) and negative likelihood ratio (NLR) (0.07)., Conclusions: US assessment of VWT could be a non-invasive tool for diagnosis and follow-up in CVD, and an interesting in vivo parameter complementing diameter and reflux measures, with a view to optimizing treatment. It could help to determine i) the energy level necessary in case of endovenous laser ablation, and ii) the sclerosing agent concentration in case of chemical ablation.

A retrospective study was conducted to evaluate the effects of a multi-component training program with strength machines on physical performance and reversibility of frailty in elderly people. At the end of the program, a significant increase in physical performance was observed and there was a significant decrease in frailty., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Breast cancer brain metastases are a challenging daily practice, and the biological link between gene mutations and metastatic spread to the brain remains to be determined. Here, we performed a meta-analysis on genomic data obtained from primary tumors, extracerebral metastases and brain metastases, to identify gene alterations associated with metastatic processes in the brain. Articles with relevant findings were selected using Medline via PubMed, from January 1999 up to February 2022. A critical review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement (PRISMA). Fifty-seven publications were selected for this meta-analysis, including 37,218 patients in all, 11,906 primary tumor samples, 5541 extracerebral metastasis samples, and 1485 brain metastasis samples. We report the overall and sub-group prevalence of gene mutations, including comparisons between primary tumors, extracerebral metastases and brain metastases. In particular, we identified six genes with a higher mutation prevalence in brain metastases than in extracerebral metastases, with a potential role in metastatic processes in the brain: ESR1, ERBB2, EGFR, PTEN, BRCA2 and NOTCH1 . We discuss here the therapeutic implications. Our results underline the added value of obtaining biopsies from brain metastases to fully explore their biology, in order to develop personalized treatments.

This study will address the prevalence of pre-therapeutic sarcopenia (PS) and its clinical impact during cancer treatment among adult cancer patients ≥ 18 years of age. A meta-analysis (MA) with random-effect models was performed via a MEDLINE systematic review, according to the PRISMA statement, focusing on articles published before February 2022 that reported observational studies and clinical trials on the prevalence of PS and the following outcomes: overall survival (OS), progression-free survival (PFS), post-operative complications (POC), toxicities (TOX), and nosocomial infections (NI). A total of 65,936 patients (mean age: 45.7-85 y) with various cancer sites and extensions and various treatment modes were included. Mainly defined by CT scan-based loss of muscle mass only, the pooled prevalence of PS was 38.0%. The pooled relative risks were 1.97, 1.76, 2.70, 1.47, and 1.76 for OS, PFS, POC, TOX, and NI, respectively (moderate-to-high heterogeneity, I 2 : 58-85%). Consensus-based algorithm definitions of sarcopenia, integrating low muscle mass and low levels of muscular strength and/or physical performance, lowered the prevalence (22%) and heterogeneity (I 2 < 50%). They also increased the predictive values with RRs ranging from 2.31 (OS) to 3.52 (POC). PS among cancer patients is prevalent and strongly associated with poor outcomes during cancer treatment, especially when considering a consensus-based algorithm approach.

Anti-HER2 therapies have dramatically improved the prognosis of human epidermal growth factor receptor 2 (HER2)-overexpressing cancers. However, the correlation between the HER2 copy number and the response rate to anti-HER2 remains unclear. Here, following the PRISMA method, we performed a meta-analysis in the neoadjuvant setting in breast cancer to study the association between the HER2 amplification level and the pathological complete response (pCR) to anti-HER2 therapies. Nine articles (four clinical trials, five observational studies) were retrieved after full-text screening, involving 11,238 women with locally advanced breast cancer in the neoadjuvant setting. The median HER2/CEP17 ratio cut-off value was 5.0 ± 5.0 (min-max = 1.0-14.0). For the overall population, the median pCR rate was 48% using the random effect model. The studies were categorized in quartiles as follows: ≤2 (Class 1); 2.1 to 5.0 (Class 2); 5.1 to 7.0 (Class 3); and >7.0 (Class 4). After grouping, the pCR rates were 33%, 49%, 57%, and 79%, respectively. When we excluded the study by Greenwell et al., which accounted for 90% of the patients, using the same quartiles, we still observed an increasing rate of pCR as the HER2/CEP17 ratio increased. This is the first meta-analysis demonstrating the relationship between the HER2 amplification level and the percentage of pCR in the neoadjuvant setting among women with HER2-overexpressing breast cancer, with potential therapeutic applications.

Massive Open Online Courses (MOOCs) are gaining popularity in education while classroom lectures are being deserted, especially after COVID-19 pandemic. Their added value in teaching undergraduate medical students remains to be confirmed. This study evaluated a MOOC devoted to undergraduate medical students in a blended oncology-teaching university program. It was the first to target undergraduate medical students in oncology at its beginning. Students were asked to participate in a survey before and after MOOC to explore interactions between their characteristics and final grades, 65% of the participating students belonged to the rich class. 70% of the students completed the MOOC. Grades distributions were similar before and after MOOC implementation, so MOOC doesn't alter overall results. In addition, there was a positive effect of the MOOC on median grades on the immediate test. The univariate and multivariate analysis showed that socioeconomic status and student's willingness to participate interacted significantly with final results. Particularly, students' motivation and satisfaction were associated with better results; Almost 70% of students asked for blended learning. E-learning is reliable to teach oncology to undergraduate medical students. The success is directly linked to students' willingness to participate, and can be improved using blended methods including tutorials., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Objectives: We assessed the direct and indirect effects between six geriatric domains and 6- and 12-month mortality in older cancer patients., Study Design and Setting: We included cancer patients aged ≥70 years from the Elderly Cancer Patients cohort, referred for geriatric assessment between 2007 and 2016. We used structural equation modelling to examine the interrelationships between six geriatric domains (function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support) and the direct and indirect relationships between these domains, the cancer stage, site, and treatment on the one hand and mortality on the other., Results: The analysis included 1,434 patients (mean age: 80 ± 5.6 years; women: 48%; main cancer sites: digestive tract [36.2%], urinary tract and prostate [26.6%], and breast [16.5%]; metastatic cancer: 48%). Direct relationships to 6- and 12-month mortality were identified for functional impairment (standardized coefficient [SC]: 0.37 [P < 0.001] and 0.32 [P < 0.001], respectively), poor nutritional status (SC: 0.11 [P = 0.005] and 0.14 [P = 0.001]), poor social support (SC = 0.07 [P = 0.08] and 0.09 [P = 0.02]), cancer site, stage, and treatment. The effects of comorbidities, cognitive impairment, and depression on mortality were mediated by functional and nutritional status., Conclusion: In older cancer patients, functional and nutritional impairments were the strongest direct prognostic geriatric factors for mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Telemedicine technology is a growing field, especially in the context of the COVID-19 pandemic. Consult Station (Health for Development) is the first telemedicine device enabling completely remote medical consultations, including the concurrent collection of clinical parameters and videos., Objective: Our aim was to collect data on the multisite urban and suburban implementation of the Consult Station for primary care and assess its contribution to health care pathways in areas with a low density of medical services., Methods: In a proof-of-concept multisite prospective cohort study, 2134 consecutive patients had teleconsultations. Consultation characteristics were analyzed from both the patient and practitioner perspective., Results: In this study, the main users of Consult Station were younger women consulting for low-severity seasonal infections. Interestingly, hypertension, diabetes, and preventive medical consultations were almost absent, while they accounted for almost 50% of consultations with a general practitioner (GP). We showed that for all regions where the Consult Station was implemented, the number of consultations increased as GP density decreased. The study of practitioner characteristics showed GPs from metropolitan areas are motivated to work with this device remotely, with a high level of technology acceptability., Conclusions: The multisite implementation of Consult Station booths is suitable for primary care and could also address the challenge of "medical deserts." In addition, further studies should be performed to evaluate the possible contribution of Consult Station booths to limiting work absenteeism., (©Géraldine Falgarone, Guilhem Bousquet, Arnaud Wilmet, Albert Brizio, Valérie Faure, Celestin Guillouet, Franck Baudino, Isabelle Roque, Samuel Mayol, Frederic Pamoukjian. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.05.2022.)

Context: Although antiangiogenic treatments and immunotherapies have significantly improved the prognosis of metastatic renal cell carcinoma (RCC), many patients will develop resistance, leading to treatment failure. Genetic tumor heterogeneity is a major cause of this resistance., Objective: To perform a meta-analysis of genomic data for clear-cell RCC obtained from primary tumors and metastases to assess the prevalence of gene mutations and copy number alterations (CNAs)., Evidence Acquisition: Articles were selected from Medline and Embase libraries using the search algorithm ("Kidney Neoplasms"[Mesh] OR "Renal Cell Carcinoma") AND ("Genomics"[Mesh] OR "Mutation") from January 1999 to February 2021. A critical review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Ninety-three publications were selected for inclusion in this meta-analysis., Evidence Synthesis: Our meta-analysis included a total 14 696 patients, 14 299 primary tumor samples, and 969 metastatic samples. We evaluated the overall and subgroup prevalence of gene mutations and CNAs, including comparisons between primary tumors and metastases. In particular, for metastases we observed that the mutation prevalence was significantly more marked for ten genes compared to primary tumors, with no or little heterogeneity across studies. The VHL mutation prevalence increased significantly from 64% in primary tumors to 75% in metastases (p < 0.001). There was a significant increase in CNA prevalence from primary tumors to metastases for chromosomes 1p36.11, 9p21.3, and 18 in terms of losses, and for chromosomes 1q21.3, 7q36.3, 8q, and 20q11.21 in terms of gains. CDKN2A, also called p16 and involved in cell-cycle progression, is located at the 9p21.3 locus and was lost in 76% of metastatic samples. ASXL1, located on 20p11.21 and amplified in 50% of metastatic RCCs compared to 21% of primary tumors (p < 0.001), is closely linked to BAP1 function., Conclusions: Our results underline the added value of preferential biopsies on RCC metastases to fully explore the biology of metastatic disease for therapeutic purposes., Patient Summary: We reviewed the literature on genetic mutations in primary tumors and metastatic lesions in kidney cancer. Our pooled results for all the relevant studies show a higher level of mutations in metastases than in primary tumors. This highlights the importance of taking biopsies of metastases to analyze genetic mutations and potentially guide selection of the most suitable treatment strategy., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Pre-therapeutic factors associated with overall survival (OS) among older patients ≥70 years with metastatic pancreatic cancer (mPC) are not known. This was a retrospective single-centre cohort study in Paris including 159 consecutive older patients with mPC between 2000 and 2018. Alongside geriatric parameters, specific comorbidities, cancer-related data and chemotherapy regimens were retrieved. Cox multivariate models were run to assess predictors for OS. The median age was 80 years, 52% were women, 21.5% had diabetes, and 48% had pancreatic head cancer and 72% liver metastases. 62% of the patients ( n = 99) received chemotherapy, among which the gemcitabine + nab-paclitaxel (GnP) regimen was the most frequent (72%). Median OS [95%CI] was 7.40 [5.60-10.0] and 1.40 [0.90-2.20] months respectively for patients with and without chemotherapy. The GnP regimen (aHR [95%CI] = 0.47 [0.25-0.89], p = 0.02) and diabetes (aHR = 0.44 [0.24-0.77], p = 0.004) (or anti-diabetic therapy) were multivariate protective factors for death, while ECOG-PS, liver metastases, and the neutrophil cell count were multivariate risk factors for death. In the chemotherapy group, ECOG-PS, number of metastatic sites and the GnP remained significantly associated with OS. Our study confirms the feasibility and efficacy of chemotherapy and the protective effects of diabetes among older patients with mPC.

Purpose: We set out to demonstrate the benefit of using dose-intense cisplatin-based neoadjuvant chemotherapy in terms of overall survival and progression-free survival., Methods: We searched through MEDLINE and Cochrane Library databases up to May 2021 to identify randomized clinical trials comparing the benefit of using cisplatin-based neoadjuvant chemotherapy followed by local treatment with local treatment alone for the treatment of locally advanced cervical cancer. The PRISMA statement was applied., Results: Twenty-two randomized clinical trials were retrieved between 1991 and 2019, corresponding to 3632 women with FIGO stages IB2-IVA cervical cancer. More than 50% of the randomized clinical trials were assessed as having a low risk of bias. There was no benefit of neoadjuvant chemotherapy on overall survival, but there was significant heterogeneity across studies (I 2 = 45%, p = 0.01). In contrast, dose-intense cisplatin at over 72.5 mg/m 2 /3 weeks was significantly associated with increased overall survival (RR = 0.87, p < 0.05) with no heterogeneity across the pooled studies (I 2 = 36%, p = 0.11). The survival benefit was even greater when cisplatin was administered at a dose over 105 mg/m 2 /3 weeks (RR = 0.79, p < 0.05)., Conclusion: Even though radiotherapy combined with weekly cisplatin-based chemotherapy remains standard of care for the treatment of locally advanced cervical cancer, our meta-analysis makes it possible to consider the use of dose-intense cisplatin-based neoadjuvant chemotherapy when local treatment is suboptimal and opens perspectives for designing new clinical trials in this setting. Neoadjuvant chemotherapy could be proposed when surgery is local treatment instead of standard chemoradiotherapy for the treatment of locally advanced cervical cancer.

Systematic molecular profiling and targeted therapy (TKI) have changed the face of Non-Small Cell Lung Cancer (NSCLC) treatment. However, there are no specific recommendations to address the prescription of TKI for older patients. A multidisciplinary task force from the French Society of Geriatric Oncology (SoFOG) and the French Society of Pulmonology/Oncology Group (SPLF/GOLF) conducted a systematic review from May 2010 to May 2021. Protocol registered in Prospero under number CRD42021224103. Three key questions were selected for older patients with NSCLC: (1) to whom TKI can be proposed, (2) for whom monotherapy should be favored, and (3) to whom a combination of TKI can be proposed. Among the 534 references isolated, 52 were included for the guidelines. The expert panel analysis concluded: (1) osimertinib 80 mg/day is recommended as a first-line treatment for older patients with the EGFR mutation; (2) full-dose first generation TKI, such as erlotinib or gefitinib, is feasible; (3) ALK and ROS1 rearrangement studies including older patients were too scarce to conclude on any definitive recommendations; and (4) given the actual data, TKI should be prescribed as monotherapy. Malnutrition, functional decline, and the number of comorbidities should be assessed primarily before TKI initiation.

We aimed to assess the prognostic value of the pre-operative GRADE score for long-term survival among older adults undergoing major surgery for digestive or non-breast gynaecological cancers. Between 2013 and 2019, 136 consecutive older adults with cancer were prospectively recruited from the PF-EC cohort study before major cancer surgery and underwent a geriatric assessment. The GRADE score includes weight loss, gait speed at the threshold of 0.8 m/s, cancer site and cancer extension. The primary outcome was post-operative 5-year mortality. Patients were classified as low risk (GRADE ≤ 8) or high risk (GRADE > 8) on the basis of the median score. A Cox multivariate proportional hazards regression model was performed to assess the association between pre-operative factors and 5-year mortality expressed by adjusted hazard ratio (aHR) and 95% CI. The median age was 80 years, 52% were men, 73% had colorectal cancer. The 30-day post-operative severe complication rate (Clavien-Dindo ≥ 3) was 37%. The 5-year post-operative mortality rate was 34.5%. A GRADE score ≥ 8 (aHR = 2.64 [1.34-5.21], p = 0.0002) was associated with post-operative mortality after adjustment for Body Mass Index < 21 kg/m 2 and Instrumental Activities of Daily Living <3/4. By combining very simple geriatric and cancer parameters, the pre-operative GRADE score provides a discriminant prognosis and could help to choose the most suitable treatment strategy for older cancer patients, avoiding under or over-treatment.

Background: Nutritional impairment is common in cancer patients and is associated with poor outcomes. Only few studies focused on cachexia. We assessed the prevalence of cachexia in older cancer patients, identified associated risk factors, and evaluated its impact on 6 month overall mortality., Methods: A French nationwide cross-sectional survey (performed in 55 geriatric oncology clinics) of older cancer patients aged ≥70 referred for geriatric assessment prior to treatment choice and initiation. Demographic, clinical, and nutritional data were collected. The first outcome was cachexia, defined as loss of more than 5% of bodyweight over the previous 6 months, or a body mass index below 20 kg/m 2 with weight loss of more than 2%, or sarcopenia (an impaired Strength, Assistance with walking, Rise from chair, Climb stairs and Falls score) with weight loss of more than 2%. The second outcome was 6 month overall mortality., Results: Of the 1030 patients included in the analysis [median age (interquartile range): 83 (79-87); males: 48%; metastatic cancer: 42%; main cancer sites: digestive tract (29%) and breast (16%)], 534 [52% (95% confidence interval: 49-55%)] had cachexia. In the multivariate analysis, patients with breast (P < 0.001), gynaecologic (P < 0.001), urinary (P < 0.001), skin (P < 0.001), and haematological cancers (P = 0.006) were less likely to have cachexia than patients with colorectal cancer. Patients with upper gastrointestinal tract cancers (including liver and pancreatic cancers; P = 0.052), with previous surgery for cancer (P = 0.001), with metastases (P = 0.047), poor performance status (≥2; P < 0.001), low food intake (P < 0.001), unfeasible timed up-and-go test (P = 0.002), cognitive disorders (P = 0.03) or risk of depression (P = 0.005), were more likely to have cachexia. At 6 months, 194 (20.5%) deaths were observed. Cachexia was associated with 6 month mortality risk (adjusted hazard ratio = 1.49; 95% confidence interval: 1.05-2.11) independently of age, in/outpatient status, cancer site, metastatic status, cancer treatment, dependency, cognition, and number of daily medications., Conclusions: More than half of older patients with cancer managed in geriatric oncology clinics had cachexia. The factors associated with cachexia were upper gastrointestinal tract cancer, metastases, poor performance status, poor mobility, previous surgery for cancer, cognitive disorders, a risk of depression, and low food intake. Cachexia was independently associated with 6 month mortality., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

The prognostic value of the CRP to albumin ratio (CAR) among older adults with cancer is not known. Six hundred and three older outpatients with cancer and undergoing geriatric assessment before therapeutic decisions were prospectively recruited from the PF-EC cohort study. Serum albumin levels, serum CRP levels and the CAR were prospectively recorded at baseline, and at each consultation thereafter, as follows: 1, 3, 6, 9, 12, 18, 24 and 36 months. Frailty was defined as a G8-index ≤ 14. The primary endpoint was longitudinal variation in the CAR during the study follow-up. Two clusters in the longitudinal trajectories of the CAR were identified, one favourable, with lower values and better overall survival (cluster A), and the second with higher values and less favourable overall survival (cluster B). The median CAR [95% CI] for clusters A and B were respectively: 0.17 [0.04-0.48] and 0.26 [0.04-0.79] at baseline ( p = 0.01), and 0.18 [0.02-3.17] and 0.76 [0.03-6.87] during the study follow-up ( p < 0.0001). Cluster B was associated with the frailest patients with metastatic disease, mainly driven by a high CRP level at baseline, and low albumin during the study follow-up. Our study results suggest that the most risk-prone patients have a cancer-cachexia trajectory.

Background: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities., Objectives: to assess the efficacy and safety of regorafenib at it's approved dose in the older population., Patients and Methods: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off)., Results: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy., Conclusion: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

COVID-19 pneumonia can be severe, with an unpredictable evolution and high mortality prevalence in older patients. The diagnosis is usually performed by RT-PCR or CT chest scan. Lung ultrasonography (LUS) has been proposed as an alternative method to monitor patients with COVID-19 pneumonia. To assess the diagnostic performance of LUS, we performed LUS using a portable device and adapting a protocol already used in Acute Respiratory Syndrome. We used the score obtained with the index we created to assess for LUS diagnostic performance as compared to lung CT chest scan and to predict for oxygen requirements. Daily bedside LUS was easy to perform and microbiologically safe. LUS was 89% sensitive and 100% specific in predicting CT chest scan abnormalities, and 95% sensitive and 67% specific in detecting oxygen requirements. This is the first report on the diagnostic performance of LUS as compared to CT chest scan for the diagnosis of COVID-19 pneumonia and assessments of oxygen requirements by LUS. LUS could help in the orientation of dyspneic patients to intensive care. It could also be proposed when there is limited access to CT scan in the context of a pandemic crisis, or to implement clinical lung examinations for outpatient follow-up.

Background: Overweight and obesity are associated with adverse health outcomes. However, substantial literature suggests that they are associated with longer survival among older people. This "obesity paradox" remains controversial. In the context of cancer, the association between overweight/obesity and mortality is complicated by concomitant weight loss (WL). Sex differences in the relation between BMI (in kg/m2) and survival have also been observed., Objectives: We studied whether a high BMI was associated with better survival, and whether the association differed by sex, in older patients with cancer., Methods: We studied patients aged ≥70 y from the ELCAPA (Elderly Cancer Patients) prospective open cohort (2007-2016; 10 geriatric oncology clinics, Greater Paris urban area). The endpoints were 12- and 60-mo mortality. We created a variable combining BMI at cancer diagnosis and WL in the previous 6 mo, and considered 4 BMI categories-underweight (BMI < 22.5), normal weight (BMI = 22.5-24.9), overweight (BMI = 25-29.9), and obesity (BMI ≥ 30)-and 3 WL categories-<5% (minimal), 5% to <10% (moderate), and ≥10% (severe). Univariate and multivariate Cox proportional hazards analyses were conducted in men and women., Results: A total of 2071 patients were included (mean age: 81 y; women: 48%; underweight: 30%; normal weight: 23%; overweight: 33%; obesity: 14%; predominant cancer sites: colorectal (18%) and breast (16%); patients with metastases: 49%). By multivariate analysis, obese women with WL < 5% had a lower 60-mo mortality risk than normal-weight women with WL < 5% (adjusted HR: 0.56; 95% CI: 0.37, 0.86; P = 0.012). Overweight/obese women with WL ≥ 5% did not have a lower mortality risk than normal-weight women with WL < 5%. Overweight and obese men did not have a lower mortality risk, irrespective of WL., Conclusions: By taking account of prediagnosis WL, only older obese women with cancer with minimal WL had a lower mortality risk than their counterparts with normal weight.This trial was registered at clinicaltrials.gov as NCT02884375., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: To assess factors associated with one-month mortality among older inpatients with Covid-19., Results: The mean age was 78 ± 7.8 years, 55.5% were men, CT scan lung damage was observed in 76% of the patients (mild 23%, moderate 38%, extensive 22%, and severe 7%). The mortality rate was 26%. Dependency/Activities of Daily Living (ADL) score ≤ 5/6, D-Dimers, LDH, and no anticoagulation by reference for curative were independently associated with one-month mortality. A score derived from the multivariate model showed good calibration and very good discrimination (Harrell's C index [95%CI] = 0.83 [0.79-0.87])., Conclusion: ADL-dependency, high serum levels of D-Dimers and LDH and the absence of anticoagulation were independently associated with one-month mortality among older inpatients with Covid-19., Methods: 108 consecutive older inpatients aged 65 and over with Covid-19 confirmed by RT-PCR and/or typical CT chest scan were prospectively included in a French single-centre cohort study from March to April 2020. A systematic geriatric assessment was performed. Covariates were lymphocyte count, serum levels of albumin, C-Reactive Protein, D-Dimers and Lactate Dehydrogenase (LDH), anticoagulation level, and exposure to the hydroxychloroquine and azithromycin combined therapy. Cox uni- and multivariate proportional-hazard regressions were performed to identify predictors of one-month mortality.

Background: to distinguish direct and indirect pathways to frailty phenotype, and quantify associations between two frailty components (i.e., sarcopenia and cachexia) regarding mortality and morbidity in older adults with cancer., Methods: all consecutive older outpatients with cancer were included in a prospective two-centre cohort study between 2013 and 2017 and had geriatric assessment. We used the frailty phenotype. Sarcopenia and cachexia were built as latent variables by including observed variables related to physical performances and related to nutrition and inflammation respectively. Structural equation modelling was used to distinguish between direct and indirect effects of the frailty parameters on the risk of death (Model 1) and the risk of morbidity (defined by unplanned hospitalization and/or disability and/or a fall; Model 2). The root mean square error of approximation (RMSEA) and the comparative fit index (CFI) were used to assess the model fit., Results: 603 older outpatients were included (mean age: 81.2 ± 6.1; women: 54%; frailty phenotype: 58%). The 6-month mortality and morbidity rates were 18% and 64%, respectively. The fit was good for both models (RMSEA and CFI = 0.029 [0.017-0.039] and 0.99 for Model 1, and 0.028 [0.017-0.039] and 0.99 for Model 2, respectively). Sarcopenia and cachexia were both directly and significantly associated with 6-month mortality (β sarcopenia = 0.18, p = 0.01; β cachexia = 0.52, p < 0.0001) and morbidity (β sarcopenia = 0.37, p < 0.0001; β cachexia = 0.19, p < 0.02)., Conclusions: sarcopenia and cachexia had a direct pathway with 6-month mortality and morbidity in older cancer patients.

Background: To develop, validate, and assess the clinical impact of a clinical score to predict a 6-month mortality risk among older cancer patients., Results: The mean age was 81.2 ± 6.1 years (women: 54%, various cancers, metastatic cancer: 45%). The score, namely the GRADE, included two geriatric variables (unintentional weight loss, impaired mobility), two oncological variables (cancer site, cancer extension), and exclusively supportive care. Up to a 14% risk of early death, the decision curves suggest that cancer treatment should be instated., Conclusion: We have developed and validated a simple score, easy to implement in daily oncological practice, to predict early death among older cancer patients which could guide oncologists in their treatment decisions., Methods: 603 outpatients prospectively included in the Physical Frailty in Elderly Cancer patients cohort study. We created a multivariate prediction model by evaluating the strength of the individual components of the Geriatric Assessment regarding risk of death at 6 months. Each component was evaluated by univariate analysis and the significant variables ( P ≤ 0.20) were carried on as covariates in the multivariate cox proportion hazard analysis. The beta coefficients from the model were used to build a point-based scoring system. Clinical impact was assessed using decision curves.