Treatment Of Older Patients Research Articles

171P Association of breast cancer therapy with cognitive decline in older women with early breast cancer: Findings from the CLIMB study

Studies investigating the long-term effects of breast cancer treatment on cognition in older breast cancer survivors are lacking, even though intact cognition is a highly valued outcome by the older population. Specifically, concern has been raised about detrimental effects of endocrine therapy (ET) on cognition. Therefore, we aimed to investigate longitudinal cognitive functioning and predictors of cognitive decline in older women treated for breast cancer. We prospectively enrolled Dutch women aged 70 years or older with stage I-III breast cancer in the CLIMB study. The Mini-Mental State Examination (MMSE) was performed at baseline, and 9, 15 and 27 months. Longitudinal trajectories of MMSE scores were analyzed for the minimal clinically important difference (2.3 points) in the whole cohort and in women treated with ET. To compare MMSE scores between patients with impaired and normal cognition and to identify the association between possible predictors and cognitive decline, linear mixed models were estimated. Among the 273 participants, mean age was 75.8 years (standard deviation (SD) 5.2) and 48% received adjuvant ET. Mean MMSE at baseline was 28.24 (SD 1.95). Cognition did not decline over time to clinically important differences in the whole cohort or in women receiving ET. MMSE scores of women with pretreatment cognitive impairments improved over time (significant interaction terms) in the whole cohort and in women receiving ET. Older age, lower education level and impaired mobility were independently associated with cognitive decline, but this decline was not clinically significant. Cognition of older women with early breast cancer did not decline up until two years after treatment initiation, irrespective of endocrine therapy. Our findings might indicate that fear of declining cognition does not justify de-escalation of breast cancer treatment in older patients.

TB in the elderly: clinical features and outcomes.

BACKGROUND: TB in low-incidence countries is characterised by changes in age distribution towards larger numbers of cases among the elderly.OBJECTIVES: To investigate clinical features and outcomes of TB treatment in older patients and identify predictors of poor outcome.METHODS: Multicentre retrospective study of new TB cases from 53 hospitals included in the registry of the Integrated Tuberculosis Research Programme of the Spanish Society of Pulmonology and Thoracic Surgery (Sociedad Española de Neumología y Cirugía Torácica) between 2006 and 2020.RESULTS: We identified 731 patients aged ≥75 years from a cohort of 7,505 patients with TB. In the elderly, weight loss, disseminated disease and normal X-rays or infiltrates without cavitation were more common. All-cause mortality was 16% (5% of deaths due to TB). The elderly had higher rates of toxicity (6.7%) and hospital admissions (36%). In the multivariate analysis of predictors of TB mortality in ≥75-year-olds, only weight, age and treatment with non-standard regimens remained significant.CONCLUSIONS: TB in older patients needs more attention and remains a challenge because of a lack of specific clinical and radiological features. Standard treatment is effective, although mortality is higher than in young patients. Low weight, non-standard regimens and age are significant predictors of TB mortality.

Assessment of physical stress during the perioperative period of endoscopic submucosal dissection.

The advantage of endoscopic submucosal dissection (ESD) is that it is less invasive than surgery. ESD is one of the best treatments for older patients as surgery in this age group of patients is difficult. However, it is unclear how much lower the physical stress of ESD is compared with that of surgery. Thus, objective methods are required to assess physical stress in patients who have undergone ESD. The current review of ESD aimed to summarize the recent advancements in the assessment of physical stress during the perioperative period, focusing on changes in energy metabolism and serum opsonic activity (SOA). Based on metabolic changes, resting energy expenditure (REE) was measured using an indirect calorimeter. The stress factor calculated from the REE and the basal energy expenditure computed using the Harris-Benedict equation can be used to assess physical stress. SOA was assessed using the chemiluminescence method, wherein the use of chemiluminescent probes (i.e., lucigenin and luminol) allowed quantification of reactive oxygen species generated by neutrophils. Using an auto luminescence analyzer, the results were evaluated based on the maximum light emission and area under the emission curve. These quantifiable results revealed the minimal invasiveness of ESD.

Medical management of older patients with lung cancer.

Lung cancer is the most common cause of cancer-related death globally. In addition, its incidence increases with age, with approximately half of all cases diagnosed in patients aged ≥70. Molecular targeted therapies and immunotherapies for advanced non-small-cell lung cancer have markedly improved outcomes over the past two decades. Despite the high incidence of lung cancer in older people, most trials excluded such patients from enrollment. Therefore, the optimal treatment strategies for older patients remain unclear. The present review summarizes the published literature and provides guidance on the treatment of older patients with lung cancer within three broad stages: (i) early-stage lung cancer, (ii) locally advanced lung cancer and (iii) metastatic lung cancer. We also discuss the use of the latest evidence for older patients.

Outcomes in older patients with metastatic epithelial ovarian cancer: Are we providing equitable care? (600)

Outcomes in older patients with metastatic epithelial ovarian cancer: Are we providing equitable care? (600)

Adult Medulloblastoma: Updates on Current Management and Future Perspectives.

Simple SummaryAdult medulloblastoma is an extremely rare tumor of the central nervous system. Standard multimodal treatment, comprising maximal safe surgical resection followed by craniospinal radiotherapy and multi-agent chemotherapy, can improve the prognosis of this disease, producing, however, important acute and long-term toxicities. Herein, we review the state of the art for adult medulloblastoma diagnosis and treatment, presenting novel molecular advances and their therapeutic implications and discussing the central role of hub centers to guarantee the highest quality of care and a better overall outcome for this rare tumor.Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa belonging to the family of primitive neuro-ectodermic tumors (PNET). MB generally occurs in pediatric age, but in 14–30% of cases, it affects the adults, mostly below the age of 40, with an incidence of 0.6 per million per year, representing about 0.4–1% of tumors of the nervous system in adults. Unlike pediatric MB, robust prospective trials are scarce for the post-puberal population, due to the low incidence of MB in adolescent and young adults. Thus, current MB treatments for older patients are largely extrapolated from the pediatric experience, but the transferability and applicability of these paradigms to adults remain an open question. Adult MB is distinct from MB in children from a molecular and clinical perspective. Here, we review the management of adult MB, reporting the recent published literature focusing on the effectiveness of upfront chemotherapy, the development of targeted therapies, and the potential role of a reduced dose of radiotherapy in treating this disease.

Differences in Treatment Modalities and Prognosis of Elderly Patients with Ovarian Cancer: A Two-Center Propensity Score-Matched Study.

Simple SummaryThe standard of care for patients with ovarian cancer is well established. While the prognosis of younger patients has improved significantly, the survival of older patients remains low. Reasons accounting for the poor survival among older patients are controversial. This study aimed to describe the difference in treatment received by older patients in China and to evaluate the prognostic significance of both chronological age and different treatment modalities using a propensity score-matched cohort. Cytoreduction with no residual tumor and the completion of adjuvant chemotherapy were the most important prognostic factors. Chronological age, however, had no influence on recurrence. This relatively large case–controlled study provides evidence that the difference between the standard of care and the treatment of older patients was the main reason that handicaps the efficacy of therapy.Background: The prognosis of older patients with ovarian cancer is poor. We evaluated the effect of chronological age and different treatment characteristics on the prognosis of older patients with ovarian cancer; Methods: The study retrospectively analyzed patients aged over 60 years who underwent cytoreduction followed by platinum-based adjuvant chemotherapy between January 2011 and December 2019 in two national centers in China. Propensity score matching (PSM, 1:1) was performed to stratify the comorbidity- and treatment-related factors. The Kaplan–Meier method was employed to estimate progression-free survival (PFS) in the original cohort and the cohort after PSM; Results: A total of 324 patients were evaluated. The Age ≥ 70 group often received more neoadjuvant chemotherapy (62.3% vs. 31.2%, p < 0.001), more discontinuation of adjuvant chemotherapy (31.2% vs. 10.8%, p < 0.001), and had more severe chemotherapy-related toxicity (45.6% vs. 34.2%, p = 0.040) than the Age < 70 group. After matching, the PFS of the Age < 70 group was not significantly different from the Age ≥ 70 group (median PFS = 12.4 and 11.9 months, respectively, p = 0.850). Furthermore, the advanced FIGO stage, non-R0 cytoreduction, and discontinuation of adjuvant chemotherapy were all found to be poor prognostic factors. Serum albumin level <40 g/L (HR = 2.441, p = 0.018) and age ≥ 70 years (HR = 2.639, p = 0.008) led to more severe chemotherapy-related toxicity. Additionally, poor renal function (HR = 5.128, p = 0.002) was in association with discontinuation of adjuvant chemotherapy; Conclusions: The chronological age of older patients cannot be seen as a poor prognostic factor. Older patients may benefit most from R0 cytoreduction followed by the completion of chemotherapy. Postoperative poor renal function and serum albumin level <40 g/L may help predict the discontinuation of adjuvant chemotherapy.

Validation of the 70-gene signature test (MammaPrint) to identify patients with breast cancer aged ≥ 70 years with ultralow risk of distant recurrence: A population-based cohort study

IntroductionWhen risk estimation in older patients with hormone receptor positive breast cancer (HR + BC) is based on the same factors as in younger patients, age-related factors regarding recurrence risk and other-cause mortality are not considered. Genomic risk assessment could help identify patients with ultralow risk BC who can forgo adjuvant treatment. However, assessment tools should be validated specifically for older patients. This study aims to determine whether the 70-gene signature test (MammaPrint) can identify patients with HR + BC aged ≥70 years with ultralow risk for distant recurrence. Materials and MethodsInclusion criteria: ≥70 years; invasive HR + BC; T1-2N0-3M0. Exclusion criteria: HER2 + BC; neoadjuvant therapy. MammaPrint assays were performed following standardized protocols. Clinical risk was determined with St. Gallen risk classification.Primary endpoint was 10-year cumulative incidence rate of distant recurrence in relation to genomic risk. Subdistribution hazard ratios (sHR) were estimated from Fine and Gray analyses. Multivariate analyses were adjusted for adjuvant endocrine therapy and clinical risk. ResultsThis study included 418 patients, median age 78 years (interquartile range [IQR] 73–83). Sixty percent of patients were treated with endocrine therapy. MammaPrint classified 50 patients as MammaPrint-ultralow, 224 patients as MammaPrint-low, and 144 patients as MammaPrint-high risk. Regarding clinical risk, 50 patients were classified low, 237 intermediate, and 131 high. Discordance was observed between clinical and genomic risk in 14 MammaPrint-ultralow risk patients who were high clinical risk, and 84 patients who were MammaPrint-high risk, but low or intermediate clinical risk. Median follow-up was 9.2 years (IQR 7.9–10.5).The 10-year distant recurrence rate was 17% (95% confidence interval [CI] 11–23) in MammaPrint-high risk patients, 8% (4–12) in MammaPrint-low (HR 0.46; 95%CI 0.25–0.84), and 2% (0–6) in MammaPrint-ultralow risk patients (HR 0.11; 95%CI 0.02–0.81). After adjustment for clinical risk and endocrine therapy, MammaPrint-high risk patients still had significantly higher 10-year distant recurrence rate than MammaPrint-low (sHR 0.49; 95%CI 0.26–0.90) and MammaPrint-ultralow patients (sHR 0.12; 95%CI 0.02–0.85). Of the 14 MammaPrint-ultralow, high clinical risk patients none developed a distant recurrence. DiscussionThese data add to the evidence validating MammaPrint's ultralow risk threshold. Even in high clinical risk patients, MammaPrint-ultralow risk patients remained recurrence-free ten years after diagnosis. These findings justify future studies into using MammaPrint to individualize adjuvant treatment in older patients.

Is there evidence of age bias in breast cancer health care professionals’ treatment of older patients?

ObjectivesDespite NICE (2009; 2018) guidelines to treat breast cancer patients ‘irrespective of age’, older women experience differential treatment and worse outcomes beyond that which can be explained by patient health or patient choice. Research has evidenced the prevalence of ageism and identified the role of implicit bias in reflecting and perhaps perpetuating disparities across society, including in healthcare. Yet age bias has rarely been considered as an explanatory factor in poorer outcomes for older breast cancer patients. MethodsThis mixed methods study explored age bias amongst breast cancer HCPs through four components: 1) An implicit associations test (31 HCPs)2) A treatment recommendations questionnaire (46 HCPs).3) An attitudes about older patients questionnaire (31 HCPs).4) A treatment recommendations interview (20 HCPs). ResultsThis study showed that breast cancer HCPs held negative implicit associations towards older women; HCPs were less likely to recommend surgery for older patients; some HCPs held assumptions that older patients are more afraid, less willing and able to be involved in decision-making, and are less willing and able to cope with being informed of a poor treatment prognosis; and conditions which disproportionately affect older patients, such as dementia, are not always well understood by breast cancer HCPs. ConclusionsThese results indicate that there are elements of age bias present amongst breast cancer HCPs. The study's findings of age-based assumptions and a poorer understanding of conditions which disproportionately affect older patients align with patterns of differential treatment towards older breast cancer patients suggesting that age bias may be, at least in part, driving differential treatment.

An assessment of left-digit bias in the treatment of older patients with potentially curable rectal cancer

BackgroundPatient age is associated with poorer rectal cancer treatment compliance. However, it is unknown whether left-digit bias (disproportionate influence of leftmost age digit) influences this association. MethodsThe patients diagnosed with stage I–III rectal cancer between 2006 to 2017 in the National Cancer Database were identified. The association between age and receipt of guideline-adherent care was assessed using mixed-effects multivariable analyses. ResultsAmong 97,960 patients, 46.2% received guideline-adherent overall treatment and 73.3% underwent guideline-adherent surgical resection. Of those who underwent guideline-adherent surgery, 86.4% received guideline-adherent radiotherapy and 56.6% received guideline-adherent chemotherapy. After risk-adjustment, each decade increase in age was associated with 36% decreased odds of guideline-adherent therapy (odds ratio = 0.64, 95% confidence interval = 0.63–0.65). Patients aged 58 to 59 (odds ratio = 1.15, 95% confidence interval = 1.02–1.27) and 78 to 79 (odds ratio = 1.28, 95% confidence interval = 1.08–1.51) had higher odds of guideline-adherent overall treatment compared with patients aged 60 and 80, respectively. However, there were no significant differences in the receipt of guideline-adherent treatment between patients aged 60 vs 61–62 and 80 vs 81–82. ConclusionOlder patients with rectal cancer are less likely to receive guideline-adherent care, and a left-digit bias is present. Geriatric assessment-guided treatment decisions could help mitigate this bias.

Immune Checkpoint Inhibitors: The Unexplored Landscape of Geriatric Oncology.

Cancer is classically considered a disease of aging, with over half of all new cancer diagnoses occurring in patients over the age of 65 years. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet the participation of older adults with cancer in ICI trials has been suboptimal, particularly at the extremes of age. Despite significant improvement in treatment response and an improved toxicity profile when compared with conventional cytotoxic chemotherapies, many cancers develop resistance to ICIs, and these drugs are not free of toxicities. This becomes particularly important in the setting of older adults with cancer, who are generally frailer and harbor more comorbidities than do their younger counterparts. Immunosenescence, a concept involving age-related changes in immune function, may also play a role in differential responses to ICI treatment in older patients. Data on ICI treatment response in older adult with cancers remains inconclusive, with multiple studies revealing conflicting results. The molecular mechanisms underlying response to ICIs in older cancer patients are poorly understood, and predictors of response that can delineate responders from non-responders remain to be elucidated. In this review, we explore the unique geriatric oncology population by analyzing existing retrospective datasets, and we also sought to highlight potential cellular, inflammatory, and molecular changes associated with aging as potential biomarkers for response to ICIs.

AN OVERVIEW OF THE MANAGEMENT OF ANKLE FRACTURES IN GERIATRIC POPULATION

Background : Recent clinical studies have identified a significant increase in the incidence and severity of ankle fractures in the elderly population. Kannus et al reported that between 1970 and 2000 there was a three-fold increase in the number of ankle fractures among Finnish patients over 70 years old [1]. In addition, the authors demonstrated an increase in the more severe Lauge-Hansen supination-eversion stage four fracture, compared to more stable ankle fracture patterns in this elderly patient population. In the data available from the United States, ankle fractures have been reported to occur in as many as 8.3 per 1000 Medicare recipients, a figure that appears to be rising steadily [2] . There continues to be controversy within the orthopaedic community regarding the optimal management of geriatric ankle fractures. Operative fixation has been proven to be a safe and effective method of managing unstable ankle fractures in younger patients [3 ] . However, certain authors have recommended conservative treatment in older patients, based on poor surgical outcomes secondary to osteoporosis, diabetes, peripheral vascular disease and skin issues commonly seen with advanced age [4, 5, 6, 7] . Recommendations on appropriate management also appear to differ based on geographical location, evidenced by a recent study by Koval et al [2] . The authors demonstrated that the percentage of ankle fractures in patients older than 65 treated with surgical stabilization varied considerably in various parts of our country. The current paper reviews the complex issues associated with ankle fractures affecting the geriatric patient population, focusing on risk factors for fracture and surgical versus nonsurgical management. 30 patientsMethods: with closed displaced bimalleolar ankle fractures presenting to Dr B R Ambedkar medical college casualty from September 2020 to February 2022 who underwent surgery were taken into the study . The maximum studyResults: population belonged to the geriatric age group .At the end of follow-up (64.8%) had excellent clinical result, (35.2%) had good clinical result, and no patient had a poor functional outcome. For the radiological assessment, there were 20 patients (66.6%) with excellent, 7 (23.3%) with good, 3(10.%) with fair, while none with poor resu :Conclusion Treatment bimalleolar ankle is challenging because of limited soft tissue cover, poor bone quality with osteoporosis and less vascularity. There are various treatment options for these fractures starting from closed reduction with casting to open reduction and internal fixation with a plate. The excellent functional results and lack of soft tissue complications suggest that a surgical management with CC screw and plating should be considered as an option in bimalleolar ankle fractures. A balance between anatomical reduction and soft tissue stripping is required to avoid any complications.

INTENSIVE SYSTOLIC BLOOD PRESSURE TARGET IN OLDER HYPERTENSIVE PATIENTS - IS IT BENEFICIAL?

Objective: The prevalence of hypertension increases with age, and the treatment in older patients is more challenging due to their comorbidities and frailty. The ideal target for systolic blood pressure (SBP) remains unclear. This study analysed how intensive blood-pressure control in older patients reflects cardiovascular events and hypertensive-mediated organ damage (HMOD) reversion. Design and method: We present a descriptive and retrospective study, including patients over 60 years, followed in a central hospital hypertension clinic over two years. One group had an SBP target &lt; 130mmHg (intensive treatment), while the other had a more lenient target. Stroke, acute coronary syndromes, acute decompensated heart failure or death from cardiovascular causes were the evaluated cardiovascular events. The analysed HMOD included microalbuminuria, echocardiographic left ventricular hypertrophy (LVH) and chronic kidney disease (CKD). Results: 150 of 296 patients were selected. 30% were over 80 years old. Cardiovascular events occurred in 9% of patients with SBP &lt; 130mmHg and in 7% of patients with &gt; 130mmHg. More than half of patients (64%) had HMOD. LVH was the most frequent HMOD (78%), followed by microalbuminuria (44,8%) and CKD (37,5%). 61% of patients in intensive treatment had HMOD versus 66% with SBP target &gt; 130mmHg. Reversion of HMOD occurred in 83% of patients with standard treatment compared with 17,6% in the intensive treatment group. Regarding previous cardiovascular events in the studied population, stroke was the most prevalent (56%), followed by acute coronary syndrome (41%). The majority (59%) of these very high cardiovascular risk patients presented an SBP target &lt; 130mmHg. Conclusions: In this study, intensive treatment in older patients did not appear to benefit cardiovascular events prevention and HMOD reversion. However, the HMOD reversion might have been underestimated due to patient discharge prior to further evaluation. In patients with previous cardiovascular events, a tendency to select an intensive treatment seems evident.

Long-Term In-Center Nocturnal Hemodialysis Improves Renal Anemia and Malnutrition and Life Quality of Older Patients with Chronic Renal Failure.

BackgroundOlder patients with chronic renal failure (CRF) which currently is referred to as end-stage renal disease (ESRD) are associated with higher mortality. In-center nocturnal dialysis (INHD) is a new blood purification model, which is characterized by longer sessions and nighttime administration. However, no data for the efficacy of INHD in older patients with ESRD are available. This study is to analyze the effect of INHD in the treatment of older patients with ESRD.MethodsA retrospective, observational study was conducted in a university teaching hospital. Seventy-two patients with ESRD receiving INHD were enrolled. They were divided into the older ESRD patients (age ≥60) group (n = 22) and the non-older ESRD patients (age <60) group (n = 50). The causes of older ESRD patients and non-older ESRD patients receiving INHD were analyzed. Differences of laboratory test indicators of older patients with ESRD before INHD and after INHD were compared. Quality of life for older ESRD patients receiving INHD was assessed by using the Kidney Disease Quality of Life-36 Instrument (KDQOL-36).ResultsSerum concentration of hemoglobin and serum concentration of albumin of older patients with ESRD increased significantly after INHD (p < 0.05). There were similar results in the non-older cohort (p ≤ 0.05). Scores of five KDQOL-36 subscales increased significantly after INHD (p ≤ 0.001) indicated that the quality of life for old patients with ESRD was significantly improved after INHD.ConclusionINHD is an effective blood purification therapy that can improve the condition of renal anemia, and it may provide a potential positive impact in the malnutrition of older and non-older patients with ESRD. INHD can improve the quality of life of older patients with ESRD. The results will provide a basis for formulating new policies of blood purification therapy for older patients.

A decision curve analysis of the clinical usefulness of a two-step frailty assessment strategy in older patients with prostate, breast, colorectal, or lung cancer.

12011 Background: Geriatric Assessment (GA) is recommended to assess the health status and select the most appropriate cancer treatment in older patients. However, GA is resource- and time-consuming. Thus, a two-step approach using frailty screening has been recommended. We aimed to evaluate the usefulness of frailty screening over GA for identifying unfit individuals who need GA and reducing unnecessary GA in fit individuals in a population of older outpatients with cancer. Methods: We analyzed patients age 70 and older with prostate, breast, colorectal, or lung cancer included in the multicenter, prospective ELCAPA cohort study (NCT02884375) between February 2007 and December 2019. All patients had a GA at inclusion. GA was the reference test. We defined unfit patients as those having at least one abnormal score in the following domains: functional status, mobility, comorbidity, cognition, mental health status, nutrition, and polypharmacy. We defined unfit patients according to the G8 and modified G8 scores using the recommended cut-offs (≤ 14 out of 17 points and ≥ 6 out of 35 points, respectively). We calculated each screening tool's sensitivity, specificity, and positive and negative predictive values. We used decision curve analysis to estimate the net benefit (the percentage of patients found to be unfit) of screening over GA. We assessed the avoided unnecessary GAs for each screening tool (reducing unnecessary GA in fit patients without decreasing the number of unfit patients undergoing [necessary] GA). We calculated these estimates across different threshold probabilities corresponding to the value of missing an unfit patient compared to exposing a fit patient to an unnecessary GA. A probability of 0.33 indicated that missing an unfit patient was two times worse than referring a fit patient to an unnecessary GA. A probability of 0.50 indicated that missing an unfit patient was the same as exposing a fit patient to an unnecessary GA. Results: We analyzed 1,648 patients with prostate (15%), breast (52%), colorectal (22%), or lung cancer (11%). The median age was 81 years, 559 patients (34%) had metastatic disease, and 1,428 patients (87%) were unfit. The sensitivity (95% CI) and specificity were 85% (84-87) and 59% (57-61) for the G8 score, and 86% (84-87) and 60% (58-63) for the modified G8 score. With a threshold probability of 0.33, the net benefit was 0.71 for the G8 score, 0.72 for the modified G8 score, and 0.80 for GA. With a threshold probability of 0.50, the net benefit was 0.68 for the G8 score, 0.69 for the modified G8 score, and 0.73 for GA. We did not observe a reduction in unnecessary GA of screening tools over GA. Conclusions: Frailty screening tools showed good diagnostic performances. However, our findings suggest that the GA-for-all strategy provides the higher clinical benefit in older patients with cancer.

Current treatment status of older patients with gynecological cancers.

The percentage of older patients with gynecological malignancies has recently been on the rise. Although prospective studies focusing on the treatment of older patients have been conducted for ovarian cancer, mainly in Europe, there have been scarce literature on cervical and endometrial cancers, and information on their treatment is currently lacking. One of the characteristics of older patients is that not only their performance status but also other factors, such as physical, mental and social factors, cause a large variability, and individual differences in their response to treatments. One of the major issues in the treatment of older patients is how to objectively measure these individual differences and link them to the appropriate treatment selection. In this review, clinical evidence for the guided treatment of older patients with gynecological cancer will be reviewed.

The feasibility and acceptability of a home-based, virtual exercise intervention for older patients with hepatocellular carcinoma: protocol for a non-randomised feasibility study (TELEX-Liver Cancer)

BackgroundThe number of incident cases and deaths from primary liver cancer, predominantly hepatocellular carcinoma (HCC), has increased markedly in the last two decades. HCC is generally diagnosed at an advanced stage, and most new cases are in people aged over 70 years with age-related comorbidities. Treatment options are often limited, with most patients receiving palliative treatment or supportive care only. As a consequence, maintaining quality of life (QoL) through symptom management is critically important and is a core objective of clinical care. Strong evidence supports the efficacy of supervised exercise training for addressing certain cancer-related symptoms, including QoL, physical function, and fatigue. However, there are many barriers to implementing supervised exercise programmes within cancer care pathways, including economic pressures on healthcare systems and personal barriers for patients. Recent advances in technology allow patients to exercise at home under the ‘virtual’ supervision of an exercise professional through videoconferencing software (termed ‘telehealth exercise’). Despite its potential, there are uncertainties relating to the feasibility, acceptability, and safety of telehealth exercise in people living with HCC.MethodsThis is a protocol for a prospective, single-centre, single-arm, pretest-posttest feasibility trial. We aim to recruit 20 patients aged 60 years or older who have received treatment for HCC and are undergoing routine clinical monitoring. Patients will be invited to take part in two online, home-based, group exercise sessions per week for 10 consecutive weeks. The ‘virtual’ exercise sessions will be delivered in real time by an exercise professional through videoconferencing software. Each session will comprise 30 min of aerobic and resistance exercise performed at a moderate intensity, as guided by the 10-point Borg rating of perceived exertion scale. Feasibility outcomes include recruitment, retention, adherence, intervention fidelity, and safety. Acceptability of the intervention will be assessed using a mixed-methods approach via monthly online surveys and an exit telephone interview. Physical function, accelerometry-measured physical activity, mid-upper arm circumference, and patient-reported outcome measures (PROMS) will be assessed before and after the intervention to determine the feasibility of assessing outcome measures. Physical function outcomes include the short physical performance battery and Liver Frailty Index. PROMS include the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire, Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire, Activities-specific Balance Confidence scale, Hospital Anxiety and Depression Scale, and the Godin Leisure-Time Exercise Questionnaire.DiscussionThis mixed-methods study will address uncertainties relating to the feasibility and acceptability of delivering live, online, home-based, group exercise sessions to patients with HCC. The findings will inform whether any modifications are required to refine and optimise the intervention, and the assessment of outcome measures will provide information on the likely size and variability of intervention effects. Collectively, the data generated will inform the design of a subsequent, adequately powered, randomised controlled trial to evaluate the efficacy of the telehealth exercise intervention.Trial registrationISRCTN14411809

Risk of tuberculosis infection and serial changes in interferon-gamma release assays in elderly patients with psoriasis receiving biologic therapy.

Elderly patients constitute a significant proportion of patients with psoriasis. Nonetheless, treatment for older patients is more challenging than that for younger ones. Biologic agents are preferable to other systemic drugs for elderly patients with moderate-to-severe psoriasis owing to their high efficacy and favorable tolerability. However, there are limited data on tuberculosis infection risk in elderly patients with psoriasis receiving biologic therapy. This study aimed to evaluate the risk of active tuberculosis and latent tuberculosis infection, assess the serial interferon-gamma release assay results, and evaluate treatment compliance and adverse effects of latent tuberculosis infection treatment in elderly patients with psoriasis on biologic therapy. In this single-center retrospective study, medical charts of elderly patients (age ≥ 65 years) with psoriasis who were treated with a biologic agent (guselkumab, adalimumab, secukinumab, or ustekinumab) between January 2015 and December 2020 were reviewed. We analyzed the results of chest X-rays and those of whole-blood interferon-gamma release assays performed for latent tuberculosis infection screening at baseline (IGRA0) and subsequently at follow-up after initiating biologic therapy (IGRA1). In total, 90 patients underwent IGRA0; 46 (51.11%) of them had latent tuberculosis infection before starting biologic therapy. Overall, four and two patients experienced seroconversion and active tuberculosis during biologic therapy, respectively. The interferon-gamma release assay reversion rate was 29.1%, and the interferon-gamma level significantly decreased in all patients after latent tuberculosis infection treatment (p=0.004). Latent tuberculosis infection treatment was well tolerated in elderly patients (completion rate, 100%). The risk of latent tuberculosis infection in elderly patients with psoriasis on biologic therapy was comparable to that previously reported for all age groups. However, the active tuberculosis rate was relatively higher.

Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities

BackgroundGLOW is a phase 3 trial evaluating the efficacy and safety of ibrutinib-venetoclax in older patients and/or those with comorbidities with previously untreated chronic lymphocytic leukemia (CLL).MethodsWe randomly assigned (1:1) patients 65 years of age or older or those 18 to 64 years of age who also had a Cumulative Illness Rating Scale (CIRS) score greater than 6 (CIRS scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or creatinine clearance of less than 70 ml/min, to ibrutinib-venetoclax (3 cycles ibrutinib lead-in, then 12 cycles ibrutinib-venetoclax) or chlorambucil-obinutuzumab (6 cycles). The primary end point was progression-free survival (PFS) assessed by an independent review committee. Secondary end points included undetectable minimal residual disease (uMRD), response rates, and safety.ResultsThis study enrolled 211 patients, with 106 randomly assigned to ibrutinib-venetoclax and 105 to chlorambucil-obinutuzumab. With a median follow-up of 27.7 months, there were 22 PFS events for ibrutinib-venetoclax and 67 events for chlorambucil-obinutuzumab. PFS was significantly longer for ibrutinib-venetoclax than for chlorambucil-obinutuzumab (hazard ratio, 0.216; 95% confidence interval [CI], 0.131 to 0.357; P<0.001). The improvement in PFS with ibrutinib-venetoclax was consistent across predefined subgroups, including patients 65 years of age or older or with a CIRS score greater than 6. The best uMRD rate in bone marrow by next-generation sequencing was significantly higher for ibrutinib-venetoclax (55.7%) than for chlorambucil-obinutuzumab (21.0%; P<0.001). The proportion of patients with sustained uMRD in peripheral blood from 3 to 12 months after end of treatment was 84.5% for ibrutinib-venetoclax and 29.3% for chlorambucil-obinutuzumab. Four patients treated with ibrutinib-venetoclax required subsequent therapy compared with 27 patients receiving chlorambucil-obinutuzumab (hazard ratio, 0.143; 95% CI, 0.050 to 0.410). Adverse events grade 3 or greater occurred for 80 (75.5%) and 73 (69.5%) patients receiving ibrutinib-venetoclax and chlorambucil-obinutuzumab, respectively, with neutropenia being most common in both arms (37 [34.9%] and 52 [49.5%]). There were 11 (10.4%) and 12 (11.4%) all-cause deaths in the ibrutinib-venetoclax and chlorambucil-obinutuzumab arms, respectively.ConclusionsIbrutinib-venetoclax, an all-oral, once-daily, fixed-duration combination, demonstrated superior PFS and deeper and better sustained responses versus chlorambucil-obinutuzumab as first-line CLL treatment in older patients and/or those with comorbidities. (Funded by Janssen Research & Development, LLC, and Pharmacyclics; ClinicalTrials.gov number, NCT03462719.)

Elotuzumab: no benefit for older patients with newly diagnosed multiple myeloma

Major progress has been made in the treatment of older patients (≥65 years) with newly diagnosed multiple myeloma. To date, continuous lenalidomide-based regimens are considered as standard of care for transplantation-ineligible patients with newly diagnosed multiple myeloma.1 In the past 10 years, immunotherapy was established as a new cornerstone of myeloma therapy, in addition to proteasome inhibitors and immunomodulatory drugs. The incorporation of daratumumab, a monoclonal antibody targeting CD38, with lenalidomide and dexamethasone led to progression-free and overall survival improvement in older patients with newly diagnosed multiple myeloma.