Energy expenditure profiles and the risk of early limiting toxicity in older patients with cancer: The ELCAPA-25 prospective cohort survey.

BACKGROUND & AIMS: Predicting the risk of early limiting toxicity (ELT) is major challenge for the clinician seeking an effective, safe treatment for older patients with cancer. The Cancer and Aging Research Group (CARG) and CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) toxicity scores were designed to predict chemotherapy-related toxicity. Elevated resting energy expenditure (REE) may predispose to cachexia and increase ELT and mortality in older patients with cancer. The primary objective was to assess the association between elevated REE and ELT in older patients with cancer. The secondary objectives were to assess the discriminant ability of a predictive model including REE (relative to the CARG and CRASH scores) and the prognostic value of elevated REE. METHODS: We assessed patients aged 70 or over included in the prospective ELCAPA cohort between 2014 and 2018. The inclusion criteria were a solid tumour, a measurement of REE at baseline (mREE, by indirect calorimetry), and a geriatric assessment prior to cancer treatment in a teaching hospital (Paris, France). The mREE was compared with the predicted REE (pREE), as defined by the Harris-Benedict equation. Depending on the mREE/pREE ratio, study participants were classified as hypermetabolic, hypometabolic or normometabolic. The primary endpoint was 3-month ELT, defined as any unplanned hospitalization or any event leading to dose reduction, a treatment delay of more than 7 days, or treatment discontinuation within 3 months of initiation. The secondary endpoint was the 3-month mortality rate. RESULTS: A total of 179 patients were included. The median age was 80 [interquartile range: 76-84] years, 37% of the patients were female, 81.8% had metastatic disease, 67.6% received chemotherapy, 20.7% received hormone therapy, and 11.7% received targeted therapies. According to the mREE/pREE ratio, 85 patients (47%) were hypermetabolic, 63 (35%) were normometabolic, and 31 (18%) were hypometabolic. Sixty patients (33.5%; 95% confidence interval (CI): 26.7-40.9) experienced ELT. The discriminant ability (as assessed by the C-index) of a multivariate model including REE and adjustment factors was 0.82 [95%CI: 0.73-0.91]. In comparison, the discriminant ability of the CARG and CRASH models was 0.57 [0.45-0.68] and 0.51 [0.40-0.62], respectively. In our model, hypermetabolism was an independent risk factor for ELT (adjusted odds ratio = 2.44; 95%CI: 1.02-5.80). Other risk factors were the cancer type and stage, the treatment protocol, a clinical diagnosis of depression, the presence of grade 3 or 4 comorbidities, and the serum lactate dehydrogenase level. CONCLUSION: Hypermetabolism status is an independent predictor of ELT in older patients with cancer, relative to normometabolic status. Baseline REE measurement might improve the ELT risk assessment and decision-making process.

Predicting Frailty and Geriatric Interventions in Older Cancer Patients: Performance of Two Screening Tools for Seven Frailty Definitions-ELCAPA Cohort.

Screening tools have been developed to identify patients warranting a complete geriatric assessment (GA). However, GA lacks standardization and does not capture important aspects of geriatric oncology practice. We measured and compared the diagnostic performance of screening tools G8 and modified G8 according to multiple clinically relevant reference standards. We included 1136 cancer patients ≥ 70 years old referred for GA (ELCAPA cohort; median age, 80 years; males, 52%; main locations: digestive (36.3%), breast (16%), and urinary tract (14.8%); metastases, 43.5%). Area under the receiver operating characteristic curve (AUROC) estimates were compared between both tools against: (1) the detection of ≥1 or (2) ≥2 GA impairments, (3) the prescription of ≥1 geriatric intervention and the identification of an unfit profile according to (4) a latent class typology, expert-based classifications from (5) Balducci, (6) the International Society of Geriatric Oncology task force (SIOG), or using (7) a GA frailty index according to the Rockwood accumulation of deficits principle. AUROC values were ≥0.80 for both tools under all tested definitions. They were statistically significantly higher for the modified G8 for six reference standards: ≥1 GA impairment (0.93 vs. 0.89), ≥2 GA impairments (0.90 vs. 0.87), ≥1 geriatric intervention (0.85 vs. 0.81), unfit according to Balducci (0.86 vs. 0.80) and SIOG classifications (0.88 vs. 0.83), and according to the GA frailty index (0.86 vs. 0.84). Our findings demonstrate the robustness of both screening tools against different reference standards, with evidence of better diagnostic performance of the modified G8.

Depressive Symptom Profiles and Survival in Older Patients with Cancer: Latent Class Analysis of the ELCAPA Cohort Study.

BACKGROUND: The expression of depressive symptoms in older people with cancer is heterogeneous because of specific features of age or cancer comorbidity. We aimed to identify depressive symptom profiles in this population and describe the associated features including survival. MATERIALS AND METHODS: Patients ≥70 years who were referred to geriatric oncology clinics were prospectively included in the ELCAPA study. In this subanalysis, depressive symptoms were used as indicators in a latent class analysis. Multinomial multivariable logistic regression and Cox models examined the association of each class with baseline characteristics and mortality. RESULTS: For the 847 complete-case patients included (median age, 79 years; interquartile range, 76-84; women, 47.9%), we identified five depressive symptom classes: "no depression/somatic only" (38.8%), "no depression/pauci-symptomatic" (26.4%), "severe depression" (20%), "mild depression" (11.8%), and "demoralization" (3%). Compared with the no depression/pauci-symptomatic class, the no depression/somatic only and severe depression classes were characterized by more frequent comorbidities with poorer functional status and higher levels of inflammation. "Severe" and "mild" depression classes also featured poorer nutritional status, more medications, and more frequent falls. Severe depression was associated with poor social support, inpatient status, and increased risk of mortality at 1 year (adjusted hazard ratio, 1.62, 95% confidence interval, 1.06-2.48) and 3 years (adjusted hazard ratio, 1.49; 95% confidence interval, 1.06-2.10). CONCLUSION: A data-driven approach based on depressive symptoms identified five different depressive symptom profiles, including demoralization, in older patients with cancer. Severe depression was independently and substantially associated with poor survival. IMPLICATIONS FOR PRACTICE: Older patients with cancer present with distinct profiles of depressive symptomatology, including different severity levels of depression and the demoralization syndrome. Clinicians should use a systematic assessment of depressive symptoms to adequately highlight these distinct profiles. Geriatric and oncological features are differently associated with these profiles. For instance, severe depression was associated with more frequent comorbidities with poorer functional, poor nutritional status, polypharmacy, frequent falls, inpatient status and poor social support. Also, severe depression was independently and substantially associated with poor survival so that the identification and management of depression should be considered a high priority in this population.

[Tyrosine kinase inhibiting the VEGF pathway and elderly people: Tolerance, pre-treatment assessment and side effects management]. / Inhibiteurs de tyrosine kinase ciblant l'angiogenèse et sujets âgés : tolérance, évaluation pré-thérapeutique et gestion des effets indésirables.

Angiogenesis inhibition is a major antitumor strategy that has emerged during the last decade. Oral tyrosine kinase inhibitors (TKI) targeting the VEGF receptor, including sunitinib, sorafenib, axitinib, regorafenib, pazopanib, and vandetanib reduce tumor growth and metastasis. These agents are approved for the treatment of metastatic diseases in first or second-line. They display a narrow therapeutic index. However, data in the elderly and/or in patients with multiple illnesses remain scarce. This population is classically excluded from clinical trials. The aim of this review is to provide an overview of existing literature regarding antiangiogenic TKI tolerance in the elderly (>70 years old). We also highlight key points of the pre-therapeutic evaluation and summarize the management of common toxicities.