Value of combining biological age with assessment of individual frailty to optimize management of cancer treated with targeted therapies: model of chronic myeloid leukemia treated with tyrosine kinase inhibitors (BIO-TIMER trial).

BACKGROUND: In the era of targeted therapies, the influence of aging on cancer management varies from one patient to another. Assessing individual frailty using geriatric tools has its limitations, and is not appropriate for all patients especially the youngest one. Thus, assessing the complementary value of a potential biomarker of individual aging is a promising field of investigation. The chronic myeloid leukemia model allows us to address this question with obvious advantages: longest experience in the use of tyrosine kinase inhibitors, standardization of therapeutic management and response with minimal residual disease and no effect on age-related diseases. Therefore, the aim of the BIO-TIMER study is to assess the biological age of chronic myeloid leukemia or non-malignant cells in patients treated with tyrosine kinase inhibitors and to determine its relevance, in association or not with individual frailty to optimize the personalised management of each patient. METHODS: The BIO-TIMER study is a multi-center, prospective, longitudinal study aiming to evaluate the value of combining biological age determination by DNA methylation profile with individual frailty assessment to personalize the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Blood samples will be collected at diagnosis, 3 months and 12 months after treatment initiation. Individual frailty and quality of life will be assess at diagnosis, 6 months after treatment initiation, and then annually for 3 years. Tolerance to tyrosine kinase inhibitors will also be assessed during the 3-year follow-up. The study plans to recruit 321 patients and recruitment started in November 2023. DISCUSSION: The assessment of individual frailty should make it possible to personalize the treatment and care of patients. The BIO-TIMER study will provide new data on the role of aging in the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors, which could influence clinical decision-making. TRIAL REGISTRATION: ClinicalTrials.gov , ID NCT06130787; registered on November 14, 2023.

Prognostic Value of Routinely Measured Inflammatory Biomarkers in Older Cancer Patients: Pooled Analysis of Three Cohorts.

BACKGROUND: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. METHODS: A pooled analysis of prospective multicenter cohorts of cancer patients aged ≥70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI). RESULTS: Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17]). CONCLUSIONS: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients.

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.

Treatment guidelines of metastatic colorectal cancer in older patients from the French Society of Geriatric Oncology (SoFOG).

BACKGROUND: Several guidelines dedicated to metastatic colorectal cancer (mCRC) are available. Since 2013 no recent guidelines are specifically dedicated to older patients and based on a systematic review. MATERIALS AND METHODS: A multidisciplinary Task Force with digestive oncologists, geriatricians and methodologists from the SoFOG was formed in 2016 to update recommendations on medical treatment of mCRC based on a systematic review of publications from 2000 to 2018. Search strategy has followed a standardized protocol from the formulation of clinical questions and definition of a search algorithm to the selection of complete articles for recommendations. RESULTS: The four selected key questions were: For which older patients with mCRC can we considered: (1) Any chemotherapy, (2) Mono or poly-chemotherapy, (3) Anti-angiogenic therapy, (4) Other targeted therapy. Main recommendations for older patients are: (1) Omission of chemotherapy should be discussed with a geriatrician for patients with severe comorbidities, advanced dementia, uncontrolled psychiatric disorder or severe loss of autonomy. (2) If tumor response is not the main aim, a mono-chemotherapy with 5-fluorouracil combined with bevacizumab is recommended as first-line. (3) For patients with symptoms related to metastases or with a planned metastasis ablation, a doublet chemotherapy combined with bevacizumab or anti-EGFR antibody in the context of a RAS wild type tumor is recommended as first-line. Preliminary data suggest that regorafenib may be used, in its registered indication, in patients under 80 with a performance status of 0 and no autonomy alterations and that trifluridine-tipiracil may be used with a tight supervising of hematological function.

Prediction of docetaxel toxicity in older cancer patients: a Bayesian network approach.

Chemotherapy is an essential therapy in the fight against cancer. Polypathology and polymedication are often encountered in elderly patients, making this population especially at risk for adverse drug reactions, and particularly with cytotoxic drugs. The objective of this study was to build a model to predict high-grade toxicity in elderly patients treated with docetaxel. Data from the trial TAX-108 have been used to create the model. The variable to predict was the occurrence of grade 3 or 4 toxicity. The explanatory variables entered in the model were anthropometric and biological characteristics of patients at inclusion; fragility criteria (SMAF, CIRS-G, performance status); location of the primary tumor; chemotherapy history, radiotherapy or surgery; weekly dose of docetaxel, cumulative dose administered. A Bayesian network model was developed using a global search procedure and an Expectation-Maximization algorithm. A 10-fold cross-validation was performed. A toxicity of grade 3 or higher was observed in 54% of patients. The variables providing the most information were the primary site (19.4%), the dose per course (17.5%), and albuminemia (13.1%). The area under the curve of the model obtained after cross-validation was 74 ± 1.4%. The model built allows classifying correctly 71.21 ± 0.9% of patients in our sample in the cross-validation procedure. The sensitivity and specificity of the model were 75 and 67%, respectively, and the positive and negative predictive values were 73 and 69%. The encouraging results from this first study show that Bayesian networks could help assess the benefit-risk ratio of chemotherapy in elderly patients.

Geriatric assessment in oncology: Moving the concept forward. The 20 years of experience of the Centre Léon Bérard geriatric oncology program.

OBJECTIVES: The management of cancer in aging people remains a challenge for physicians. Specialists agree on the assistance provided by a multidimensional geriatric assessment (MGA) to guide the cancer treatment decision-making process. We aim to explore the use of MGA in treatment decision and to identify MGA parameters likely to influence the planned cancer treatment. MATERIAL AND METHODS: We conducted a single-site retrospective study in patients older than 65 years suffering from various types of cancer who underwent MGA before cancer treatment decision. Logistic regression analyses were used for identification of predictive variables. RESULTS: In the 266 patients' population, the mean age was 75.8 ±â€¯7.4 years and 155 (58%) patients were men. Patients had solid tumors (95.4%) or hematologic malignancies (4.6%). Most of patients were in advanced setting (57%). The MGA revealed malnutrition (47%), cognitive/mood impairment (48%), functional decline (53%), and led to adjust medical care through reinforcing health status and fostering successful completion of cancer treatment plan for 259 (97%) patients. The MGA changed cancer treatment in 47 (18%) patients. Functional and/or cognitive impairment, risk of falls, and polypharmacy were associated with treatment change in univariate analysis. No multivariate model was possible. CONCLUSIONS: MGA leads to modification of treatment in only few patients. However, MGA enables a better understanding of patients' strengths and weaknesses essential to improve care management. Further improvements with integration of innovative specific tools are warranted to help decision-process in the increasing complexity of treatment plans available in older adults.

Role of Geriatric Oncologists in Optimizing Care of Urological Oncology Patients.

CONTEXT: Urological cancers are common. Since the median age of diagnosis is 60-70 yr, many patients require geriatric as well as urological evaluation if treatment is to be tailored to individual health status including comorbidities and frailty. OBJECTIVE: To review the most important features of geriatric assessment and its expected benefits. We also consider ways in which collaboration between urologists and geriatricians and geriatric teams can benefit patient well-being. EVIDENCE ACQUISITION: Members of a multidisciplinary International Society of Geriatric Oncology task force reviewed articles published in 2010-2017 using search terms relevant to urological cancers, the elderly, and geriatric evaluation. The final manuscript reflects their expert consensus. EVIDENCE SYNTHESIS: Elderly patients should be managed according to their individual health status and not according to age. As a first step, screening for cognitive impairment is mandatory to establish patient competence in making decisions. Initial evaluation of health status should use a validated screening tool, the G8 screening tool being generally preferred. Abnormal scores on the G8 should lead to a geriatric assessment that evaluates comorbid conditions and functional, nutritional, mental, and medicosocial status. When patients are frail or disabled or have severe comorbidities, comprehensive geriatric assessment is required. Diagnosis of health status impairment shows the need for geriatric interventions. This overall approach is realistic in the setting of a department of urological oncology and given the involvement of a multidisciplinary team including trained nurses and other professionals and collaboration with geriatricians. Mutual education and support of all those involved in managing elderly urological cancer patients is the key to effective care. CONCLUSIONS: Advances in geriatric evaluation and cancer treatment are contributing to more appropriate management of elderly patients with urological cancers. Better understanding of the role of all participants and professional collaboration are vital to the individualization of care. PATIENT SUMMARY: Many patients with urological cancers are elderly. In those physically fit, treatment should generally be the same as that in younger patients. Some elderly cancer patients are frail and have other medical problems. Treatment in individual patients should be based on health status and patient preference.

Management of Prostate Cancer in Elderly Patients: Recommendations of a Task Force of the International Society of Geriatric Oncology.

CONTEXT: Prostate cancer is the most frequent male cancer. Since the median age of diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if treatment is to be tailored to individual circumstances including comorbidities and frailty. OBJECTIVE: To update the 2014 International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer in men aged >70 yr. The update includes new material on health status evaluation and the treatment of localised, advanced, and castrate-resistant disease. DATA ACQUISITION: A multidisciplinary SIOG task force reviewed pertinent articles published during 2013-2016 using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments, and castration-refractory/resistant disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. DATA SYNTHESIS: Elderly patients should be managed according to their individual health status and not according to age. Fit elderly patients should receive the same treatment as younger patients on the basis of international recommendations. At the initial evaluation, screening for cognitive impairment is mandatory to establish patient competence in making decisions. Initial evaluation of health status should use the validated G8 screening tool. Abnormal scores on the G8 should lead to a simplified geriatric assessment that evaluates comorbid conditions (using the Cumulative Illness Score Rating-Geriatrics scale), dependence (Activities of Daily Living) and nutritional status (via estimation of weight loss). When patients are frail or disabled or have severe comorbidities, a comprehensive geriatric assessment is needed. This may suggest additional geriatric interventions. CONCLUSIONS: Advances in geriatric evaluation and treatments for localised and advanced disease are contributing to more appropriate management of elderly patients with prostate cancer. A better understanding of the role of active surveillance for less aggressive disease is also contributing to the individualisation of care. PATIENT SUMMARY: Many men with prostate cancer are elderly. In the physically fit, treatment should be the same as in younger patients. However, some elderly prostate cancer patients are frail and have other medical problems. Treatment in the individual patient should be based on health status and patient preference.

Impact of comorbidities on the treatment of non-Hodgkin's lymphoma: a systematic review.

Treating non-Hodgkin's lymphoma in patients with comorbidities can be challenging because of possible interactions that may alter the treatment efficacy. We conducted a systematic review to determine the impact of comorbidities on various outcomes, evaluate the current data, and provide recommendations for future research. Twenty-one articles were selected. However, the study populations and design were greatly heterogeneous, and the quality of reporting was generally weak. The majority of studies demonstrated significant impact of comorbidity on survival, reporting poorer survival rates for patients with comorbidities compared to those with no comorbidities. However, the existing evidence is limited and of insufficient quality to establish solid conclusions and to guide treatment decisions. Prospective, well-designed studies are warranted.

Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study.

BACKGROUND: Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time- and resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13). PATIENTS AND METHODS: The diagnostic accuracy of the G8 and the (VES-13) were evaluated in a prospective cohort study of 1674 cancer patients accrued before treatment in 23 health care facilities. 1435 were eligible and evaluable. Outcome measures were multidimensional geriatric assessment (MGA), sensitivity (primary), specificity, negative and positive predictive values and likelihood ratios of the G8 and VES-13, and predictive factors of 1-year survival rate. RESULTS: Patient median age was 78.2 years (70-98) with a majority of females (69.8%), various types of cancer including 53.9% breast, and 75.8% Performance Status 0-1. Impaired MGA, G8, and VES-13 were 80.2%, 68.4%, and 60.2%, respectively. Mean time to complete G8 or VES-13 was about five minutes. Reproducibility of the two questionnaires was good. G8 appeared more sensitive (76.5% versus 68.7%, P =  0.0046) whereas VES-13 was more specific (74.3% versus 64.4%, P<0.0001). Abnormal G8 score (HR = 2.72), advanced stage (HR = 3.30), male sex (HR = 2.69) and poor Performance Status (HR = 3.28) were independent prognostic factors of 1-year survival. CONCLUSION: With good sensitivity and independent prognostic value on 1-year survival, the G8 questionnaire is currently one of the best screening tools available to identify older cancer patients requiring geriatric assessment, and we believe it should be implemented broadly in daily practice. Continuous research efforts should be pursued to refine the selection process of older cancer patients before potentially life-threatening therapy.

Challenging treatment decision-making in older urologic cancer patients.

PURPOSE: Cancer is the leading cause of death among patients aged 65 years and older. In this population, the cancer diagnosis is often made at a more advanced stage and worse prognosis than in younger patients. Specific mortality in older patients is superior to that reported in their younger counterparts. Moreover, the impact of curative treatment that has proven benefit in overall population may be not well studied in the sub-group of older patients. Thus, the management of cancer in the elderly is a major public health concern in most Western countries. METHODS/RESULTS: In this review, we summarize this challenging treatment decision-making in older urologic patients with prostate, kidney or bladder cancer. The estimation of life expectancy remains a difficult task. Chronological age should not be considered as the main decisive factor anymore when considering aggressive cancer treatment. Comorbidities increase the complexity of cancer management and affect survival. Multidisciplinary evaluation and comprehensive geriatrics assessment using specific scales are critical to improve the treatment decision-making and to minimize both overtreatment of low-risk disease and undertreatment of high-risk disease. When an aggressive and potential quality-of-life-threatening treatment is scheduled after this comprehensive geriatrics assessment, personalized patient care must be early predefined by the geriatric team. CONCLUSIONS: In the elderly, an enhanced support including specific geriatric assessment and management optimizes the treatment course, including preoperative optimization, prevents treatment-related complications and loss of autonomy using or not geriatrics clinic or rehabilitation units, and limits the length of hospital stay and costs.

Organizing the geriatrician/oncologist partnership: one size fits all? Practical solutions.

Cancer in elderly patients is becoming a global issue, with the aging of the population and increased incidence of cancer with aging. Older patients with cancer have unique needs that can best be addressed by the integration of geriatrics principles and oncology care. Unfortunately, the worsening shortage of oncologists and geriatricians makes the care of the older patient with cancer increasingly challenging. Practical issues to consider when creating a geriatrics/oncology partnership include the available resources in terms of interdisciplinary team members, the patient population in need, and the ability to provide primary, consultative, and/or shared care. Ultimately, creative strategies will be needed to maximize the limited availability of the geriatrician and oncologist.

Karnofsky Performance Scale (KPS) or Physical Performance Test (PPT)? That is the question.

Oncologists usually base treatment decision on the assessment of patients' performance status (PS). This study was undertaken to explore the ability of KPS to correctly assess the PS of elderly cancer patients, comparing it to a validated geriatric tool named Physical Performance Test (PPT). One single examiner assessed elderly cancer patients' PS at registration in our institution and performed the PPT on patients with KPS ≥ 60. A sample of 152 patients actually underwent PPT. A low refusal rate was observed (<5%). Most patients (82%) had a high PS (KPS ≥ 80), whereas only 20% had no health impairment according to PPT scores. Patients' gender and disease stage did not correlate with PPT scores. The KPS seems to be a less accurate tool than the PPT to assess functional status of elderly cancer patients. Then PPT could be used as an inclusion criterion instead of KPS before cancer treatment decision.

Quality of life in geriatric oncology--An evaluation of standard questionnaires in elderly men with urological malignancies.

Quality of life (QOL) is a critical issue in elderly patients with cancer. In the geriatric population, cancer is often associated with other chronic conditions possibly affecting QOL. This prospective study aimed to evaluate the validity of two QOL questionnaires, EORTC QLQ-C30 and SF-36, in older cancer patients. Seventy-two of 87 male patients with genitourinary cancer (median age, 76 years) completed the questionnaires (83% response rate). Internal consistency reliability was high (α≥0.7), except for SF-36 cognitive function (α=0.62) and QLQ-C30 general health status (α=0.57). QLQ-C30 and SF-36 appear similarly reliable for QOL assessment in this population. However, cognitive function and functional status, two factors likely to influence the value of QOL self-assessment, are poorly taken into account whereas they are correctly explored by the comprehensive geriatric assessment (CGA) procedure. QOL assessment in elderly cancer patients should therefore be associated with CGA to better meet the expectations of clinicians.

Pain tolerance and obstructive sleep apnea in the elderly.

OBJECTIVE: Patients with painful conditions often suffer from sleep disturbances. However, changes in sleep pattern per se could also influence pain tolerance. Untreated obstructive sleep apnea (OSA) causes major disturbances in sleep pattern. The aim of this study was to assess whether continuous positive airway pressure (CPAP) treatment in elderly patients with OSA would result in improved pain tolerance. DESIGN: Randomized, double-blind crossover study. SETTING: Geriatric sleep center based in Antoine Charial University Hospital (Lyon, France). PARTICIPANTS: A total of 13 consecutive OSA patients aged 70 and older randomly assigned CPAP treatment (lowCPAP versus highCPAP). Eleven patients completed the study. MEASUREMENTS: Overnight sleep recording, electrical pain tolerance assessment, and visual analog scale for sleep quality were performed. RESULTS: Both low- and highCPAP treatment significantly improved respiratory parameters. However, compared with baseline, the electrical pain tolerance score was significantly enhanced (analgesic effect) only under highCPAP treatment (21.2 ± 10.9 versus 28.4 ± 16.0; P = .03). CONCLUSION: The treatment of OSA with CPAP would have an analgesic effect. This would represent a unique outcome attributed to CPAP treatment. Given the high prevalence of both OSA and chronic pain conditions in the elderly; our findings could hold many implications for very large segments of the elderly population.

Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei in a woman native to Afghanistan.

Rhinocladiella mackenziei is a recognized cause of endemic cerebral phaeohyphomycosis in the Middle East area. Surgical resection of the abscesses and posaconazole treatment have improved the ominous prognosis of this disease. We describe the case of a native Afghan woman living in France who presented with brain abscesses due to R. mackenziei.

[Demography and epidemiology facts in geriatric oncology]. / Démographie et epidémiologie nécessaires a l'oncogériatrie.

For decades, the ageing of the French population is constant. It is about an important phenomenon with a clean active dynamics. In 2050, the persons of more than 60 years will represent 33% of the population, and the 85 years and more 7%. Jointly the incidence of the cancer increases considerably after 65 years. This conjunction makes that more than a cancer on two occurs in elderly patients. Mortality by cancer in this age bracket does not know the favorable evolution observed in young people. This is related to more advanced stages of the disease at the time of diagnosis, with the rarer use to active therapeutics. However the elderly would like as younger people to receive an effective treatment of their cancer. The general practitioner has a fundamental role to play in the early diagnosis and in the participation to the management of cancer patient.

Effects of comorbidity on screening and early diagnosis of cancer in elderly people.

There is currently little data showing that older adults can derive benefit from cancer screening. Advancing age is associated with an increasing prevalence of cancer and other chronic conditions, or comorbidity, and questions remain about the interactions between comorbidity and cancer screening in the elderly population. In this Review, we assess the available evidence on the effects of comorbidity on cancer screening in elderly individuals. In view of the high heterogeneity of existing data, consistent recommendations cannot be made. Decisions on cancer screening in older adults should be based on an appropriate assessment of each individual's health status and life expectancy, the benefits and harms of screening procedures, and patient preferences. We suggest that Comprehensive Geriatric Assessment might be a necessary step to identify candidates for cancer screening in the elderly population. Specific clinical trials should be done to improve the evidence and show the effectiveness and cost-effectiveness of cancer screening in older adults.