Precision Oncology in Older Cancer Patients: A Single-Center Experience.

In the last two decades, next-generation sequencing (NGS) has facilitated enormous progress in cancer medicine, in both diagnosis and treatment. However, the usefulness of NGS in older cancer patients is unclear. To determine the role of NGS in older cancer patients, we retrospectively assessed demographic, clinicopathologic, and disease-specific data from 100 randomly selected cancer patients (any subtype/stage) who underwent NGS testing in 2020 at our institution and compared the treatment outcomes (progression-free survival [PFS] and overall survival [OS]) in the younger and older patient cohorts (A [n = 34] and B [n = 66]: age < 70 and ≥70 years, respectively). Overall, 27% had targetable mutations, and 8% received NGS-determined targeted therapy (45% and 19% of patients with a targetable mutation in cohorts A and B, respectively; p = 0.2), of whom 38% (3% of the whole cohort) benefited from the therapy (PFS > 6 months). The median OS (from diagnosis) was 192 and 197 weeks in cohorts A and B, respectively (p = 0.08). This pilot study revealed no significant age-stratified difference in the diagnostic approach and treatment strategy. A small, but relevant, proportion of the cohort (3%) benefited from NGS-determined treatment. Nevertheless, older cancer patients with targetable mutations less frequently received targetable therapies.

[Side effects of oncology drugs in elderly patients].

INTRODUCTION: Cancer is a disease of old age with approximately 50% of new cancer cases occurring in humans aged 65 years and older and this number is expected to rise to 58% by 2030. Chemotherapy remains a standard part of cancer treatment, alongside new therapies such as immunotherapy and targeted therapies. However, older patients are at increased risk of chemotherapy-induced toxicity compared to younger adults. Various pharmacological parameters must be taken into account in the oncological treatment of older patients. Assessing age-related conditions that affect tolerability with geriatric evaluation is very important when planning chemotherapy. Several studies have shown that geriatric assessment variables can be used to identify older adults who are most at risk of severe toxicity from chemotherapy. Oral oncological therapies present several advantages. However, they also contain disadvantages, especially in older patients, which can lead to poorer efficiency or earlier discontinuation of therapy. Despite the physiological phenomena of immunosenescence and inflammaging, the data, mainly coming from subgroup analysis of meta-analyses, tends to show that immunotherapy is effective and well-tolerated even in older patients.

[Immunotherapy: also in elderly patients ?] / Immunothérapie: aussi chez le patient âgé ?

The emergence of immunotherapy has generated great enthusiasm in oncology improving the prognosis of pathologies such as melanoma, lung cancer, kidney cancer, bladder and head and neck cancers. This enthusiasm concerns also older patients in view of the good tolerance of immunotherapy in young people. However, advanced age is linked to changes in the immune system, called immunosenescence, which could have a negative impact on the efficacy and toxicity of immunotherapy treatment. Knowledge in terms of efficacy and tolerance is limited for geriatric patients, few being included in clinical studies. This article summarizes the experience of immunotherapy in large clinical trials. It appears that the immune checkpoint inhibitors are effective and well tolerated in the elderly.

L'émergence de l'immunothérapie a engendré un grand enthousiasme en oncologie en améliorant le pronostic de pathologies telles que le mélanome et les cancers pulmonaires, rénaux, vésicaux et de la sphère ORL. Cet enthousiasme concerne aussi les patients âgés au vu de la bonne tolérance de l'immunothérapie chez les jeunes. Cependant, l'âge avancé est lié à des modifications du système immunitaire, appelées immunosénescence, qui pourraient avoir un impact négatif sur l'efficacité et la toxicité du traitement par immunothérapie. Les connaissances en termes d'efficacité et de tolérance restent limitées pour les patients gériatriques, inclus en petit nombre dans les études cliniques. Cet article résume l'expérience de l'immunothérapie dans les grands essais cliniques. Il apparaît que les inhibiteurs de points de contrôle immunitaire soient efficaces et bien tolérés chez le sujet âgé.

Corticosteroid therapy in older adults with cancer: Expert recommendations from a task force of the International Society of Geriatric Oncology.

Corticosteroids are used frequently in oncology and many patients require short- or long-term corticosteroid therapy. General clinical guidelines and recommendations exist on the use of corticosteroids; however, evidence is lacking for recommendations on their appropriate use in older adult with cancer. Treatment of chemotherapy-induced nausea and vomiting (CINV) has dramatically improved over the last decade with 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists and neurokinin-1 (NK-1) receptor antagonists or a combination of both. However, corticosteroids continue to play an important role in the management of acute and delayed CINV prevention. While highly efficacious, the toxicity profile of corticosteroids must be considered, particularly in heterogeneous older patients with multiple comorbidities and polypharmacy. Guidance on corticosteroid-reducing/sparing strategies in this specific population is needed. This consensus, supported by the International Society of Geriatric Oncology, aims to provide evidence-based recommendations for the use of corticosteroid therapy in older adults with cancer.

Clinical and pathological factors and outcome of central nervous system metastasis in breast cancer.

Background: In Switzerland, approximately 6000 new breast cancer cases and 1300 deaths are reported annually. Brain metastasis from breast cancer (BMBC) has a major effect on prognosis. This study aimed to identify prognostic factors for overall survival (OS) in a cohort of Swiss patients with BMBC. This study evaluated the prognosis on older BMBC, which has not been completely addressed in the literature. Methods: We performed a retrospective chart review analysis with the primary endpoint of OS after a diagnosis of BMBC. The study population was divided into 2 groups based on an OS cut-off value of 12 months after diagnosis. Univariate and multivariate analyses of several risk factors, including age, were performed. To evaluate differences in OS according to age, we performed a secondary analysis to examine the prognostic value of clinical symptoms, metastatic pattern, and lymph node involvement in an older (≥65 years) vs. younger (<65 years) cohort. Results: From 1989 to 2019, 55 patients were identified as having BMBC, among whom 47 patients were confirmed to be dead. The median patient age was 58 years (range 25-83 years). Comorbidities were present in 45 (81.8%) patients. The median survival in the OS <12 and OS ≥12 months groups was 4.3 and 30.7 months, respectively (p<0.001). Multivariate analysis revealed no significant differences in terms of comorbidities, medication use, M-stage, and symptomatology between the 2 groups. Additionally, there was no significant difference in OS in the 2 subgroups of patients aged <65 and ≥65 years. Discussion: We concluded that age should not be a decisive factor in therapy planning for advanced breast cancer patients with BMBC.

Structural analysis of Heschl's gyrus in schizophrenia patients with auditory hallucinations.

BACKGROUND/AIMS: Heschl's gyrus (HG) is functionally involved in the genesis of auditory verbal hallucinations (AVH). This dysfunction seems to be structurally facilitated. The aim of the study was to analyze macrostructural features of HG in a group of patients reporting AVH who demonstrated white matter diffusion tensor imaging abnormalities reported previously. METHODS: 3-D anatomical MR scans were obtained (patients with and without history of AVH, controls). HG was delineated by manual segmentation. Cortical folding, absolute and relative volumes, laterality were analyzed. RESULTS: According to the literature, in the collapsed group of patients, the normal left-greater-than-right laterality of HG was attenuated. We found a trend towards a higher number of duplicated HG in hallucinating patients. We also found a bigger volume of HG in the right hemisphere in hallucinating patients. This effect was caused by gray and white matter increase. CONCLUSIONS: This is the first study on manual volumetry of HG in a group of schizophrenia patients with AVH compared to patients without AVH. In a previous analysis of the diffusion tensor imaging data of the here presented sample, we found higher directionality of the arcuate fasciculus in patients with AVH, facilitating abnormal co-activation in the auditory cortices in the hallucinating brain. As these abnormal activations are frequent in hallucinating patients, the here described volume increase of HG might be interpreted as compensatory plastic adaptations of the contralateral regions. We suggest that this volume increase of HG is caused by the symptomatology and not by the underlying disorder of schizophrenia.

Using Big Data in oncology to prospectively impact clinical patient care: A proof of concept study.

OBJECTIVE: Big Data is widely seen as a major opportunity for progress in the practice of personalized medicine, attracting the attention from medical societies and presidential teams alike as it offers a unique opportunity to enlarge the base of evidence, especially for older patients underrepresented in clinical trials. This study prospectively assessed the real-time availability of clinical cases in the Health & Research Informatics Total Cancer Care™ (TCC) database matching community patients with cancer, and the impact of such a consultation on treatment. MATERIALS AND METHODS: Patients aged 70 and older seen at the Lynn Cancer Institute (LCI) with a documented malignancy were eligible. Geriatric screening information and the oncologist's pre-consultation treatment plan were sent to Moffitt. A search for similar patients was done in TCC and additional information retrieved from Electronic Medical Records. A report summarizing the data was sent and the utility of such a consultation was assessed per email after the treatment decision. RESULTS: Thirty one patients were included. The geriatric screening was positive in 87.1% (27) of them. The oncogeriatric consultation took on average 2.2 working days. It influenced treatment in 38.7% (12), and modified it in 19.4% (6). The consultation was perceived as "somewhat" to "very useful" in 83.9% (26). CONCLUSION: This study establishes a proof of concept of the feasibility of real time use of Big Data for clinical practice. The geriatric screening and the consultation report influenced treatment in 38.7% of cases and modified it in 19.4%, which compares very well with oncogeriatric literature. Additional steps are needed to render it financially and clinically viable.