A Fab of trastuzumab to treat HER2 overexpressing breast cancer brain metastases.

Despite major therapeutic advances for two decades, including the most recently approved anti-HER2 drugs, brain metastatic localizations remain the major cause of death for women with metastatic HER2 breast cancer. The main reason is the limited drug passage of the blood-brain barrier after intravenous injection and the significant efflux of drugs, including monoclocal antibodies, after administration into the cerebrospinal fluid. We hypothesized that this efflux was linked to the presence of a FcRn receptor in the blood-brain barrier. To overcome this efflux, we engineered two Fab fragments of trastuzumab, an anti-HER2 monoclonal antibody, and did a thorough preclinical development for therapeutic translational purpose. We demonstrated the safety and equal efficacy of the Fabs with trastuzumab in vitro, and in vivo using a patient-derived xenograft model of HER2 overexpressing breast cancer. For the pharmacokinetic studies of intra-cerebrospinal fluid administration, we implemented original rat models with catheter implanted into the cisterna magna. After intraventricular administration in rats, we demonstrated that the brain-to-blood efflux of Fab was up to 10 times lower than for trastuzumab, associated with a two-fold higher brain penetration compared to trastuzumab. This Fab, capable of significantly reducing brain-to-blood efflux and enhancing brain penetration after intra-cerebrospinal fluid injection, could thus be a new and original effective drug in the treatment of HER2 breast cancer brain metastases, which will be demonstrated by a phase I clinical trial dedicated to women in resort situations.

PROM2 overexpression induces metastatic potential through epithelial-to-mesenchymal transition and ferroptosis resistance in human cancers.

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.

A Sub-Group of Kidney-Transplant Recipients with Highly Aggressive Squamous Cell Carcinoma Expressing Phosphorylated Serine392p53.

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.

[Reversibility of frailty in elderly patients thanks to a multicomponent training programme]. / Réversibilité de la fragilité chez des patients âgés grâce à un programme d'entraînement multicomposante.

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.

Safety and efficacy of immunotherapy according to the age threshold of 80 years.

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.

Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment.

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, I2: 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 (I2 < 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.

Genomics of Breast Cancer Brain Metastases: A Meta-Analysis and Therapeutic Implications.

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.

Ultrasound assessment is linked to histological vein wall thickness in chronic venous disease.

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.

HER2 Amplification Level Predicts Pathological Complete Response in the Neoadjuvant Setting of HER2-Overexpressing Breast Cancer: A Meta-Analysis and Systematic Review.

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.

A massive open online course to teach undergraduate medical students in oncology: keys of success.

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.

Correction: A Teleconsultation Device, Consult Station, for Remote Primary Care: Multisite Prospective Cohort Study.

[This corrects the article DOI: 10.2196/33507.].

Geriatric impairments were directly and indirectly associated with mortality in older patients with cancer: a structural equation analysis.

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.

Overall Survival and Prognostic Factors among Older Patients with Metastatic Pancreatic Cancer: A Retrospective Analysis Using a Hospital Database.

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.

A Teleconsultation Device, Consult Station, for Remote Primary Care: Multisite Prospective Cohort Study.

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.

Targeted Therapy for Older Patients with Non-Small Cell Lung Cancer: Systematic Review and Guidelines from the French Society of Geriatric Oncology (SoFOG) and the French-Language Society of Pulmonology (SPLF)/French-Language Oncology Group (GOLF).

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.

Dose-Intense Cisplatin-Based Neoadjuvant Chemotherapy Increases Survival in Advanced Cervical Cancer: An Up-to-Date Meta-Analysis.

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 (I2 = 45%, p = 0.01). In contrast, dose-intense cisplatin at over 72.5 mg/m2/3 weeks was significantly associated with increased overall survival (RR = 0.87, p < 0.05) with no heterogeneity across the pooled studies (I2 = 36%, p = 0.11). The survival benefit was even greater when cisplatin was administered at a dose over 105 mg/m2/3 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.

Genomics of Clear-cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

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.

Prognostic Value of Prospective Longitudinal CRP to Albumin Ratio among Older Outpatients with Cancer.

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.

Prevalence and prognostic impact of cachexia among older patients with cancer: a nationwide cross-sectional survey (NutriAgeCancer).

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/m2 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.

The Pre-Operative GRADE Score Is Associated with 5-Year Survival among Older Patients with Cancer Undergoing Surgery.

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/m2 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.