Therapy In Elderly Patients Research Articles

The comparison of short-term dual antiplatelet therapy versus standard dual antiplatelet therapy in elderly patients with coronary artery disease who underwent percutaneous coronary intervention

Abstract Introduction Elderly patients are likely to have more underlying risk factors for bleeding and the bleeding risk increases with age although dual anti-platelet therapy (DAPT) is mandatory for patients who underwent percutaneous coronary intervention (PCI) for prevention of ischemic events. Therefore, elderly patients aged 75 or older are included as minor criteria for high bleeding risk, as defined by the Academic Research Consortium for High Bleeding Risk criteria. However, only limited data have been investigated of optimal duration of DAPT for patients aged 75 or older. Purpose The aim of this study is to evaluate optimal DAPT duration for elderly patients aged 75 and older. Methods We selected 1,571 patients aged 75 and older with coronary artery disease (CAD) from the pooled database among the 5 randomized controlled trials related to DAPT duration after PCI. DAPT was consisted of clopidogrel or ticagrelor in addition to aspirin. Short-term DAPT duration was defined as 1 to 3months, and standard DAPT duration was defined as 6 to 12months after PCI. Primary outcomes were net clinical adverse outcomes (NACE), composite of major cardiovascular and cerebrovascular adverse outcomes (MACCE) and TIMI major bleeding at 1 year. The inversed probability of treatment weighting (IPTW) analysis was performed to minimize selection bias effects of pooled database. Results The NACE was not significantly different between the short-term DAPT group (3.9%) and standard DAPT group (7.6%) (HR: 0.69, 95% CI: 0.46-1.04; p=0.076) (Figure A). Moreover, MACCE was not different in both groups. However, the significant reduction of bleeding risk was observed in short-term DAPT group (1.4%) than standard DAPT group (3.4%) (hazard ratio (HR): 0.40, 95% confidential interval (CI): 0.19-0.83; p=0.015) (Figure B). These results were consistent after multivariable Cox regression analysis and IPTW analysis. Conclusions Short-term DAPT duration (1 to 3months) was found to be superior to standard DAPT duration (6 to 12months) in terms of bleeding outcomes without the increased ischemic outcomes in patients aged 75 or older with CAD who underwent PCI.

Survival benefit of guideline-directed medical therapy in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

Abstract Background Heart failure is a major cause of mortality in the elderly and heart failure-related mortality in elderly patients has increased since 2012. The evidence of guideline-directed medical therapy (GDMT), the four pillars of treatment of heart failure with reduced ejection fraction (HFrEF), remains insufficient in this population. Aim The objective of this study was to assess the survival benefit of the four pillars of GDMT in elderly patients aged ≥ 65-years-old with HFrEF. Methods MEDLINE, EMBASE and the Cochrane Library were searched from inception to 21 July 2023. The inclusion criteria were studies comparing survival between patients ≥ 65-years-old with left ventricular systolic dysfunction receiving and not receiving GDMT. Pooled prevalence, hazard ratio (HR) and risk ratio (RR) were calculated with 95% confidence interval (CI). Heterogeneity was explored through subgroup analyses based on the number of GDMT, age cut-off, sample size, ejection fraction cut-off, study type and study publication date. Results Thirty studies with 86,941 patients from 1994 to 2019 were included. The GDMT group received three drug classes in three studies, two drug classes in four studies, and at least one class in the remaining studies. There were no reported studies on elderly patients receiving four classes of GDMT. Over 5% of the elderly HFrEF patients were frail (Pooled prevelance 7%, 95%CI 2.0–14.0, I2 98%). Frail elderly patients were less likely to receive GDMT (RR 0.63, 95%CI 0.45–0.89, I2 50%, p = 0.009). There was a survival benefit of GDMT in elderly patients with HFrEF (HR 0.70, 95%CI 0.65-0.76, I2 75%, p < 0.001). Elderly patients receiving BB were more likely to develop bradycardia (RR 3.96, 95%CI 2.71-5.80, p < 0.001, I2 0%). There was no difference in the incidence of hypotension, acute renal impairment, and hypoglycemia between the GDMT and control group. The funnel plot appeared asymmetrical which suggests possible publication bias. Conclusion The use of GDMT in elderly HFrEF patients was associated with a survival benefit. Frailty may interfere with the implementation of GDMT. High quality studies are needed to guide the safety and efficacy of GDMT, and the development of guidelines on HFrEF management the in elderly according to frailty status.Forrest plot of overall survival

Comparative analysis of hypofractionated short-course versus standard radiation therapy in elderly patients with glioblastoma: analysis of nationwide database.

Hypofractionated short-course radiation therapy (SCRT) is an alternative treatment option for elderly or frail patients with newly diagnosed glioblastoma (GBM) post-surgery. This study compares survival outcomes and treatment costs between patients receiving SCRT and those undergoing standard long-course radiation therapy (LCRT). This retrospective study utilized health insurance claims and national cancer registry data from Korea to compare overall survival (OS) and treatment costs between patients receiving SCRT and LCRT across all ages and sub-group analysis within the subgroup of cases aged 65 and older from 2016 onwards, a period when intensity-modulated radiotherapy (IMRT) was widely adopted. A total of 1,598 patients were included. Median OS since the first day of radiation therapy was 10.4 months (95% CI [9.6; 12.8]) for SCRT (n = 197) versus 16.2 months (95% CI [15.5; 16.9]) for LCRT (n = 1401) respectively. Subgroup analysis using stabilized inverse probability of treatment weighting (S-IPTW) showed indicating non-inferiority in elderly patients in median OS for elderly patients (≥ 65) with 10.6 months (95% CI [8.9; 14.0]) for SCRT (n = 147) versus 13.2 months (95% CI [8.9; 14.0]) for LCRT (n = 541). The median treatment cost of SCRT is about 6,000 USD lower, 25% less than LCRT. Compliance with the standard TMZ regimen post-radiation improved OS across all age groups. Considering comparable OS and shorter treatment duration, SCRT offers a viable, cost-effective option for elderly GBM patients. Adhering to standard TMZ also contributes to OS improvement. Further research reflecting key prognostic factors is essential to refining the role of SCRT.

Perioperative management of antithrombotic therapy in elderly patients undergoing lumbar discectomy: a retrospective study on 163 patients.

The prevalence of lumbar disc herniation (LDH) has risen alongside the aging population, often necessitating neurosurgical intervention. However, managing antithrombotic medications in elderly patients with a history of major cardiovascular events (MACE) presents challenges, as treatment may require modification or cessation. This study aims to compare surgical outcomes among elderly patients receiving antithrombotic drugs and assess their impact and potential complications. The findings aim to inform the management of elderly patients with cardiovascular and spinal conditions undergoing neurosurgery. This retrospective, observational study was conducted at a single center. A total of 163 patients aged 60 or above who underwent lumbar discectomy for LDH were included. Patients were categorized into three groups based on their antithrombotic drug management: Group A (46 patients) replaced antiplatelet agents with low-dose aspirin for secondary prevention, Group B (54 patients) discontinued antiplatelet agents for primary prevention one week preoperatively and replaced them with LMWH, and Group C (63 patients) did not receive antithrombotic medication. Intraoperative blood loss, surgical time, and postoperative hospitalization were analyzed across all three groups. Continuous variables were compared between groups using the two-tailed Mann-Whitney test, with significance set at p < 0.05. No significant differences were found in intraoperative blood loss or surgical time among groups A, B, and C. Similarly, no significant differences were observed between groups B and C across all analyzed variables. No early or delayed hemorrhagic complications occurred perioperatively or during the 3-month postoperative follow-up period. The study suggests that elective discectomy surgery in patients receiving anticoagulant and antiplatelet therapies may proceed without early complications and can be safely continued perioperatively. These findings have implications for the management of elderly patients requiring neurosurgical intervention in the context of cardiovascular comorbidities.

Safety and efficacy of adipose-derived mesenchymal stem cell therapy in elderly Parkinson's disease patients: an intermediate-size expanded access program

ObjectiveThis intermediate-size expanded access program aimed to evaluate safety and clinical efficacy of multiple intravenous infusions of autologous, Hope Biosciences adipose-derived mesenchymal stem cell (HB-adMSC) therapy in elderly patients with Parkinson's disease (PD). MethodsTen eligible participants (aged 76–95 years) received six intravenous infusions each with 200MM autologous HB-adMSCs over 18 weeks, with the end of study (EOS) at week 26. Safety was assessed through adverse events (AEs) and serious adverse events (SAEs). Efficacy was measured through improvements in both motor and non-motor symptoms, utilizing scales including Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-IV, Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's disease Fatigue Scale (PFS-16), Patient Health Questionnaire-9 (PHQ-9), and Visual Analog Scale (VAS). Analysis employed paired t-tests and Minimal Clinically Important Difference (MCID) thresholds for the patient-reported outcomes. ResultsMost AEs (37 out of 46) were mild in severity, with 5 SAEs reported, none attributed to the drug. No deaths occurred. Despite lack of statistical significance across the efficacy endpoints, modest yet clinically meaningful improvements with effect size > 0.3 were observed in several secondary efficacy endpoints (MDS-UPDRS part I & III, PDQ-39, and PHQ-9) at the EOS, nearing or surpassing the established MCID values. ConclusionsThe administration of autologous 200MM HB-adMSCs was found to be safe and well-tolerated in the elderly PD population. Although not achieving statistical significance, modest clinical improvements were noted across multiple secondary endpoints. These findings underscore the safety profile of the treatment in elderly patients and highlight the importance of evaluating clinical relevance alongside statistical measures for meaningful patient outcomes. Further investigation with a larger, randomized, placebo-controlled design is warranted to validate these observations.

Assessing the efficacy and safety of combined buspirone and venlafaxine treatment in late-life depression accompanied by cognitive impairment: A randomized controlled trial

BackgroundLate-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments. ObjectiveThis study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment. MethodsA 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted. ResultsThe ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue. ConclusionThe combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

Neuropsychiatric and Cardiac Complications in Post-operative Antibiotic Therapy in Elderly Patients Undergoing Otorhinolaryngological Surgeries: A Review of Frailty Risk Indices.

With the increase in life expectancy and awareness, more otorhinolaryngologic surgeries are being performed in the elderly population. Otorhinolaryngologic surgeries like septoplasty, tympanoplasty, and dacryocystorhinostomy (DCR) surgeries are elective surgeries for improving the quality of life. However, post-operative medication can entail a risk to life or serious side effects in elderly patients. It is seen that before any surgery, the patients have undergone various tests and investigations to monitor the nephrotoxicity and hepatotoxicity primarily to gauge medication clearance and organ damage. However, the effects of various post-operative medications on the central nervous system and cardiovascular system are less well-discussed. Harmful effects of various drugs especially antibiotics given post-operatively in otorhinolaryngology on the central nervous and cardiovascular system are not frequently reported, and the underlying mechanisms may be unclear or conflicting. Older individuals have a greater chance of experiencing serious drug reactions due to physiologic changes affecting pharmacokinetic processes. Some frailty risk indices can be used to determine the cognitive and physiological conditions in geriatric patients so that the outcome of using antibiotics in the post-operative period on the neuropsychiatric and cardiovascular systems can be predicted. This review aims to summarise the research on the neurotoxic and cardiac effects of antibiotics used in otorhinolaryngology practice in the post-operative period in elderly patients, with a focus on signs of psychosis, delirium, cognitive impairment, syncope, cardiac arrest, angina-like symptoms, etc. This review also studies some frailty risk indices that can be used to predict the neuropsychiatric and cardiac side effects due to polypharmacy, especially antibiotics. Hence, post-operative risks can be predetermined and a protocol for further management can be established.

An “Older Old” Woman with Large Squamous Cell Carcinoma of the Nasal Pyramid: Excellent Response to Ultra-Hypofractionated Radiation Therapy

A 98-year-old patient with cognitive impairment and a history of squamous cell carcinoma of the nasal pyramid was referred to the radiation oncology department of our institution’s hospital given that surgery was not recommended. The lesion was sized 6 × 6 cm, ulcerated, and bleeding; was significantly impairing the patient’s health-related quality of life, causing pain; and was not responsive to analgesics, including opioids. The patient experienced deterioration of her general conditions, with a Karnofsky performance status of 40. A single radiotherapy (RT) fraction was delivered on a weekly basis for 3 weeks, up to a total dose of 21 Gy, using a VMAT technique (7 Gy/fraction). The patient was given three fractions of radiotherapy, during which she received continuous assistance due to episodes of mental disorientation and an altered sense of consciousness. One month after the conclusion of the treatment, the patient exhibited a nearly complete clinical response, with full pain relief and an improved health-related quality of life. This favourable clinical outcome was maintained for a period of four months following the conclusion of RT. A brief review was performed on the role of hypofractionated radiation therapy in elderly patients with locally advanced skin cancer of the head and neck region.

Ischemic stroke in cancer patients: possibilities of reperfusion therapy in elderly patients

Globally, stroke and malignancies represent a major public health burden. Cancer and stroke are two clinical manifestations that are related: cancer patients have twice the risk of stroke than the general population [1]. Types of cancer most commonly associated with ischemic stroke are lung cancer, pancreatic cancer, breast cancer and prostate cancer [2]. An analysis of patients with ischemic stroke and concomitant cancer who underwent inpatient treatment at the regional vascular center in Botkin Hospital. A total of 199 patients with ischemic stroke and malignancy were analyzed. 68 patients received reperfusion therapy and 131 patients did not receive reperfusion therapy. As a result of the analysis, it was concluded that reperfusion therapy is possible and necessary for patients with malignant tumors. The risk of developing extracranial hemorrhages associated with the oncological process is extremely low, and the development of intracranial hemorrhagic complications does not significantly worsen the outcome of the disease. The severity of stroke in the presence of cancer was for the most part due to the stroke itself, its size and location, and depended less on the stage of cancer.

Anti-CD19 CAR-T Cell Therapy in Elderly Patients: Multicentric Real-World Experience from GETH-TC/GELTAMO

Chimeric antigen receptor (CAR)-T cell therapy is approved for the treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, elderly patients might not be candidates for this therapy due to its toxicity, and criteria for candidate selection are lacking. Our aim was to analyze efficacy and toxicity results of CAR-T cell therapy in the population of patients 70 years and older as compared to those obtained in younger patients in the real-world setting. A multicentric retrospective study was performed including patients with R/R aggressive LBCL who received commercial CAR-T cell therapy with either tisagenlecleucel or axicabtagene ciloleucel within the Spanish Group of Hematopoietic Transplant and Cell Therapy/Spanish Group of Lymphomas and Autologous Transplant (GETH-TC/GELTAMO) centers between 2019 and 2023. As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and follow-up data was collected. Of 412 infused patients, 71 (17%) were 70 years or older. Baseline characteristics, product selection, and characteristics at apheresis (including disease status, Ann Arbor stage, revised international prognosis index (R-IPI), bulky disease, lactate dehydrogenase [LDH] and ECOG [Eastern Cooperative Group performance status]) were comparable between groups. Median time from both approval to infusion and apheresis to infusion did not differ. No differences were found between groups in overall and complete response rates at 1 and 3 months. With a median follow-up of 12.2 months (range 1-44), 12-month progression-free survival (PFS) and overall survival (OS) were comparable between groups (35.2% in <70 years vs. 35.9% in ≥70 years (P = .938) and 51.1% and 52.1% (P = .885), respectively). Age ≥70 years did not affect PFS (hazard ratio (HR) 0.98, P = .941) and OS (HR 0.97, P = .890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% of patients <70 years old and 84.5% in ≥ 70 years old (P = .408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, P = .002). In the multivariate analysis, age ≥70 years was associated with an increased risk of grade ≥3 CRS (OR 3.7, P = .013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, P = .281) or grade ≥3 (12% vs. 17%, P = .33). The proportion of patients with infections, admission to the intensive care unit within the first month, and non-relapse mortality were similar between both groups. CAR-T cell therapy in patients older than 70 years showed similar efficacy to that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grades 3-4 CRS. The need for additional strategies to reduce toxicity in this population should be addressed in future studies.

In-hospital outcomes following surgery versus conservative therapy in elderly patients with C2 fractures: a propensity score-matched analysis.

Second cervical vertebrae (C2) fractures are a common traumatic spinal injury in the elderly population. Surgical fusion and nonoperative bracing are two primary treatments for cervical instability, but the former is often withheld in the elderly due to concerns for poor postoperative outcomes arising from patient frailty. This study sought to evaluate the in-hospital differences in mortality, outcomes, and discharge disposition in elderly patients with C2 fractures undergoing surgical intervention compared with conservative therapy. The National Trauma Data Bank was queried from 2017 to 2019 for all patients aged ≥ 65 years with C2 fractures undergoing either surgical stabilization or conservative therapy. Propensity score matching was performed using k-nearest neighbors with replacement based on patient demographics, comorbidities, insurance type, injury severity, and fracture type. Group differences were compared using Student t-tests and Pearson's chi-square tests with Benjamini-Hochberg multiple comparisons correction. Subgroup analyses were performed in the 65-74, 75-79, and 80+ year age subgroups. Six thousand forty-nine patients were identified, of whom 2156 underwent surgery and 3893 received conservative treatment. Following matching, the surgery group had significantly lower mortality rates (5.52% vs 9.6%, p < 0.001), a longer mean hospital length of stay (LOS; 12.64 vs 7.49 days p < 0.001), and slightly higher rates of several complications (< 3% difference), as well as lower rates of discharge home (14.56% vs 23.52%, p < 0.001) and to hospice (1.07% vs 2.09%, p = 0.02) and a higher rate of discharge to intermediate care (68.83% vs 48.28%, p < 0.001). Similar trends in mortality and LOS were noted in all 3 subgroups. In elderly patients with C2 fractures, surgical stabilization confers a small survival advantage with a slightly higher in-hospital complication rate compared to conservative therapy. The increased rate of discharge to rehabilitation may represent better long-term prognosis following surgery. The increased risk of short-term complications is present but relatively small, thus surgery should not be withheld in patients with good long-term prognosis.

Comparison of the Clinical Outcomes Between Reperfusion and Non-Reperfusion Therapy in Elderly Patients with Acute Ischemic Stroke.

To investigate the benefit (90-day mRS score) and rate of major complications (early symptomatic intracranial hemorrhage-SICH) after reperfusion therapy (RT) (including intravenous thrombolysis -IVT and mechanical thrombectomy -MT) in patients over 80 years with acute ischemic stroke (AIS). AIS patients aged over 80 admitted to Huizhou Central People's Hospital from September 2018 to 2023 were included in this study. Data on SICH, NIHSS, and mRS were analyzed. A good prognosis was defined as a mRS ≤ 2 or recovery to pre-stroke status at 90 days. Of 209 patients, 80 received non-RT, 100 received IVT and 29 underwent MT. The non-RT group had the lowest baseline NIHSS while the MT group had the highest (non-RT 6.0 vs IVT 12.0 vs MT 18.0, P <0.001). Higher NIHSS was associated with increased SICH risk (OR 1.083, P=0.032), while RT was not (OR 5.194, P=0.129). The overall SICH rate in the RT group was higher but not significantly different after stratification by stroke severity. Poor prognosis was associated with higher admission NIHSS, stroke due to large artery atherosclerosis (LAA) combined with cardioembolism (CE), and stroke-associated pneumonia (SAP) (OR 0.902, P<0.001; OR 0.297, P=0.029; OR 0.103, P<0.001, respectively). The RT group showed a greater reduction in NIHSS (delta NIHSS) than the non-RT group (non-RT 2.0 vs IVT 4.0 vs MT 6.0, P<0.005). For severe AIS, the IVT group had a better prognosis at 90 days (non-RT 0% vs IVT 38.2%, P=0.039). No 90-day mortality difference was found between groups after stratification. Stroke severity, rather than RT, is an independent risk factor for SICH in AIS patients over 80. RT in severe stroke patients improves NIHSS at 90 days, suggesting RT is safe and effective in this demographic. Further studies with larger samples are required to confirm these findings.

Tolerability and Efficacy of Bi-temporal Electroconvulsive Therapy in Elderly Patients with Severe Mental Illness

Background: Electroconvulsive therapy (ECT) has been an effective treatment option available for elderly patients with severe mental illness; however, there are concerns related to its tolerability. Unilateral ECT has fewer cognitive adverse effects compared to bilateral ECT while efficacy with bilateral ECT is better. Aim: To evaluate the tolerability and efficacy of Bi-temporal ECT in elderly patients (&gt;60 years) with severe mental illness in a general hospital set-up. Methodology: The study was a prospective, observational study conducted in SDM College of Medical Sciences and Hospital, Dharwad with a sample size of 15 elderly patients aged above 60 years with severe mental illness. Participants were screened for psychiatric symptoms with Mini-International Neuropsychiatric Interview and assessed for severity of symptoms with Hamilton Depression Rating Scale, Young Mania Rating Scale, and Positive and Negative Syndrome Scale. Cognitive functioning was assessed by Hindi Mental Status Examination Scale and effectiveness was assessed using global functioning by Global Assessment of Functioning (GAF) Scale. Assessment was done before giving ECT and 4 weeks at follow-up. The study period was from January 2019 to December 2019. Results and Conclusions: The median age of the elderly was 61 years. Majority (66.7%) were diagnosed with mood disorder and 33.3% of the patients were diagnosed with paranoid schizophrenia. Around 47% had comorbid hypertension and 33.3% had diabetes mellitus. All the patients in the study sample received thrice weekly bi-temporal ECT in the range of 2–8 with median of 5. Significant reduction in symptomatology was observed, on comparing the scores before and after ECT with improvement in overall functioning assessed by GAF Scale. There was no decline in cognitive functioning test, although there was an improvement in the Hindi version of mini mental status examination scores at 4 weeks after discharge. By the above observations, we concluded that the use of bi-temporal ECT in elderly patients with severe mental illness was found to be safe and effective in treating.

Combined oral low-dose cyclophosphamide endocrine therapy may improve clinical response among patients with metastatic breast cancer via Tregs in TLSs

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2− advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin–eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy.

Efficacy and toxicity of BRAF targeted therapy in elderly patients with melanoma.

e23270 Background: Melanoma is the most lethal form of skin cancer which have seen drastic improvement in patient survival over the last decade. BRAF is the most common driver mutation in melanoma, seen in ≈50% of all patients (≈30% of patients &gt; 65). The use of BRAF &amp; MEK inhibitors yields high response rates, though it is limited by toxicity and development of acquired resistance. Acknowledging these limitations, we aimed at assessing the efficacy and toxicity of these agents in melanoma patients &gt; 65. Methods: We identified electronic medical records of all melanoma patients &gt; 65 that were treated with BRAF &amp; MEK inhibitors at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, treatment given, response patterns and toxicity. Results: 106 patients were identified. The median age was 71 (65-89), 55% were males. The median follow up was 28.9 months. 32 (30%) patients were treated at first line, 58 (55%) at second line and 16 (15%) at third line. 88 (83%) evaluable patients received treatment for unresectable/metastatic disease of which 84% had an objective response (60% partial response, 24% complete response). Response rate (RR) was 82%, 85% and 87% for first, second and third line respectively. RR was 86% for patients with an increased serum lactate dehydrogenase. 33% of patients had active central nervous system (CNS) metastases at treatment initiation, for whom the systemic RR was 80% and the CNS RR was 39%. The median progression free survival (PFS) was 7.9 months, with a PFS of 6, 8.3 and 13.4 months for first, second and third line respectively. The median PFS was 5.7 months for patients with active CNS disease. The median overall survival (OS) from treatment initiation was 15.7 months (12.5, 14.5, 31.9 for first, second &amp; third line respectively). The median OS for patients with CNS disease was 9.8 months. 16 patients were treated in the adjuvant setting, of which 6 (37%) finished treatment as planned, 3 stopped due to disease progression (19%) and 6 stopped due to toxicity (37%). 88% of patients experienced adverse events (AEs) of any grade, with 27% having grade 3-4 toxicity. There were no grade 5 toxicities reported. 36% of patients experienced one AE, while 52% experienced two or more. 21% of patients stopped treatment due to toxicity, 28% needed a dose reduction and 20% changed to different BRAF/MEK inhibitors. 10% of patients needed systemic corticosteroids to treat AEs. The most common toxicities seen were fever (30%), fatigue (30%), skin rash (22%), elevated liver function tests (20%), arthralgia/myalgia (15%), nausea (14%) and diarrhea (11%). 7% had decrease in cardiac ejection fraction with one grade 3 leading to treatment discontinuation. Conclusions: Treatment with BRAF &amp; MEK inhibitors is challenging in older patients, with a high prevalence of toxicity leading to treatment modifications and discontinuation. Efficacy seems to be the same as in the general population.

Fractionated external-beam radiation therapy in elderly patients.

e13764 Background: To review the outcome of elderly patients treated with fractionated external-beam radiation therapy (RT) at a privately-owned, multi-disciplinary cancer center. Methods: From January 7, 2019, to August 22, 2023, 63 elderly patients were treated with fractionated RT at California Cancer Associates for Research and Excellence (“cCARE”), a privately-owned, multi-disciplinary cancer center in Fresno, California. The median age at the time of RT was 90 y/o (range, 85-98 y/o). Twenty-three patients were female and 40 were male. Forty-six patients identified as white and 17 as non-white. Treatment sites/histologies included primary lung 10, non-melanomatous skin 6, bone metastases 6, breast 5, esophagus 5, H&amp;N 5, prostate 4, primary CNS 3, brain metastases 3, rectum 3, bladder 2, Merkel tumor 2, sarcoma 2, anus 1, liver 1, melanoma 1, multiple myeloma 1, NHL 1, pancreas 1 and stomach 1. Results: Thirty-two of the patients (51%) were treated with curative intent. The remaining 31 patients were treated for palliation. All patients were treated with fractionated RT. However, 4 patients also received a separate course of single-fraction RT. Twenty-seven patients received more than one course of RT. The median RT course was 10 fractions (range, 1-35 fractions). Most patients had previously been treated with systemic therapy. Nearly one third (31%) received systemic therapy concurrent with their RT. The majority of the patients (73%) completed their prescribed course(s) of RT. Many patients (61%) required one or more treatment breaks. The median duration of a treatment break was 1 day (range, 1-29 days). There were no grade 3 or higher RT toxicities recorded. The median follow-up since RT was 5 months (range, 1-59 months). Twenty-four patients have expired. The mediation duration from RT to death was 5 months (range, 1-32 months ). Of the remaining 39 patients, 92% were scored as clinically stable at the time of their last f/u visit. Conclusions: In our experience at cCARE, fractionated RT was administered to elderly patients and the majority completed their prescribed treatment courses. None of the patients in our review experienced clinically significant side effects (Grade 3 or higher) during their RT even in the cohort (31%) who were treated with concurrent systemic therapy. Clearly, careful patient selection and state-of-the-art RT administration is paramount. It is also highly advantageous for patients to be treated in a multi-disciplinary setting such as cCARE where seamless coordination of cancer care among radiation oncologists, medical oncologists and surgeons excels. A companion study is in process comparing the outcome of similarly matched elderly patients from our center who were treated with systemic therapy alone. We anxiously await the outcome of this vital comparison review.

Efficacy and toxicity of KIT targeted therapy in elderly patients with melanoma.

e23269 Background: Most cases of malignant melanoma are cutaneous, with ≈50% having a BRAF driver mutation that predicts response to MAPK pathway inhibitors. A small minority of melanoma cases harbor an activating KIT mutation, most notably in mucosal and acral melanomas (15-20%) and occasionally in those arising from chronic sun-damaged skin (2-3%). Only about a third of KIT mutated melanomas respond to targeted therapy with Imatinib, yet data is scarce and limited, especially in older patients. We sought to characterize the efficacy and toxicity of Imatinib in KIT-mutated melanoma patients over 65. Methods: We identified electronic medical records of patients over 65 that were treated with Imatinib for KIT mutated melanoma at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, response patterns and toxicity. Results: 10 patients were identified, 50% were males. The median age at treatment initiation was 75 years (71-100). 3 patients had cutaneous primary, 3 had Vulvar/vaginal primary, 3 had acral primary and 1 had anal canal primary. All patients had normal Lactate dehydrogenase at treatment initiation and ECOG performance status was 0-2 (median 0). 9 patients received Imatinib for stage IV disease with an overall response rate (ORR) of 55% (44% partial response, 11% complete response). Median duration of response was 4 months. Responses were seen in acral melanoma (67%), vulvar/vaginal melanoma (67%) and cutaneous melanoma (33%). Median Progression free survival was 4.3 months (1.8-44), median overall survival from treatment initiation was 22.6 months (4-64). 6 patients were treated as 2nd line with an ORR of 67% and 3 were treated as 3rd line with an ORR of 33%. There was one patient with M1d disease who did not respond to treatment either systematically or intracranially. 6 patients had Exon 11 mutations (V560D/G/E, N564S and L576P) of which 4 responded (67%). 2 had Exon 17 mutations (N822C/K) of which 1 responded (50%) and the 2 others had an Exon 14 (F681I) and Exon 13 (K642E) mutation that did not respond to treatment at all. Toxicity was moderate with 90% of patients experiencing any grade AE, yet only 1 experienced toxicity requiring dose interruption with two Grade 3 toxicities - Pneumonitis and decreased neutrophil count, leading to temporary treatment interruption, dose reduction and a course of corticosteroids. The rest of the patients experienced only Grade 1-2 toxicity. 4 patients needed dose reductions, there were no treatment discontinuations due to toxicity. Conclusions: Treatment with Imatinib for elderly KIT mutated melanoma patients is safe and well tolerated with no treatment discontinuations recorded. The response rate is encouraging yet seems to vary according to the KIT mutation present as previously reported. The duration of response is usually short-lived and alternative/combination treatments are still needed for this patient population.

Management of Portal Hypertension in the Older Patient.

Aging is a process of physiological slowing, reduced regenerative capacity and inability to maintain cellular homeostasis. World Health Organisation declared the commencement of population aging globally, largely attributed to improvement in the healthcare system with early diagnosis and effective clinical management. Liver ages similar to other organs, with reduction in size and blood flow. In this review we aim to evaluate the effect of aging in liver disease. Aging causes dysregulation of major carbohydrate, fat and protein metabolism in the liver. Age is a major risk factor for liver fibrosis accelerated by sinusoidal endothelial dysfunction and immunological disharmony. Age plays a major role in patients with liver cirrhosis and influence outcomes in patients with portal hypertension. Transient elastography may be an useful tool in the assessment of portal hypertension. Hepatic structural distortion, increased vascular resistance, state of chronic inflammation, associated comorbidities, lack of physiological reserve in the older population may aggravate portal hypertension in patients with liver cirrhosis and may result in pronounced variceal bleed. Cut-offs for other non-invasive markers of fibrosis may differ in the elderly population. Non-selective beta blockers initiated at lower dose followed by escalation are the first line of therapy in elderly patients with cirrhosis and portal hypertension, unless contraindicated. Acute variceal bleed in the elderly cirrhotic patients can be life threatening and may cause rapid exsanguination due to poor reserve and associated comorbidities. Vasoactive drugs may be associated with more adverse reactions. Early endoscopy may be warranted in the elderly patients with acute variceal bleed. Role of TIPS in the elderly cirrhotics discussed. Management of portal hypertension in the older population may pose significant challenges to the treating clinician.

Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study

BackgroundThe risk–benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of...

Current Status and Prospect of PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy in Elderly Patients with Advanced NSCLC

The incidence of cancer is closely correlated with age, as 75% of non-small cell lung cancer (NSCLC) patients are aged at least 65 years. The availability of immune checkpoint inhibitors (ICIs) has altered the available NSCLC therapeutic pattern. Limited studies on elderly patients have demonstrated that ICIs as monotherapy provide substantial benefits for patients aged 65-75 years, showing no significant difference compared to younger patients. This benefit is also observed in combination with immune-combined chemotherapy or radiotherapy. For individuals older than 75 years, the survival effect was not evident, though. Immune-related adverse events (irAEs) with ICIs alone were similar in incidence across age categories. Immune-combination chemotherapy resulted in a higher incidence of irAEs than chemotherapy alone, and patients ≥75 years of age were more likely to experience higher-grade irAEs. Besides the fact that immunosenescence in older patients influences the immune milieu in a multifaceted manner, which in turn impacts the effectiveness of immunotherapy, the prognosis is also influenced by the Eastern Cooperative Oncology Group performance status (ECOG PS) score, among other factors. For certain individuals aged ≥75 years or in poor physical health, immunotherapy combined with low-intensity chemotherapy has emerged as a viable treatment option. However, there are fewer related studies, so there should be a conscious effort to increase the number of elderly patients enrolled in the trial and a comprehensive assessment to explore individualized treatment options. To provide additional references and guidance for immunotherapy in elderly NSCLC patients and to propose new therapeutic perspectives in combination with their characteristics, this review aims to summarize and analyze the pertinent studies on the application of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors in these patients. .