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BACKGROUND: Prostate cancer is a common malignancy of the elderly, and with the aging of the population, the need is growing for therapies suitable for this age group. Lutetium-177-prostate-specific membrane antigen (Lu-PSMA), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen, enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer (mCRPC). In a recent single-arm phase II trial and a subsequent expansion cohort, a prostate-specific antigen (PSA) decline of ≥50% was observed in approximately 60% of patients receiving Lu-PSMA. Taking into account the specific challenges and potential toxicities of Lu-PSMA administration in elderly men, we sought to retrospectively analyze the safety and activity of Lu-PSMA in men aged older than 75 years with mCRPC. PATIENTS AND METHODS: The electronic medical records of 24 patients aged older than 75 years treated with Lu-PSMA "off-trial" were reviewed, and clinical data were extracted. Clinical endpoints were toxicity and activity, defined as a PSA decline ≥50%. Descriptive statistics were performed using Excel. RESULTS: The median age at treatment start was 81.7 years (range 75.1-91.9). The median number of previous treatment lines was four. The number of treatment cycles ranged from one to four; the mean administered radioactivity was 6 GBq per cycle. Treatment was generally tolerable; side effects included fatigue (n = 8, 33%), anemia (n = 7, 29%), thrombocytopenia (n = 5, 21%), and anorexia/nausea (n = 3, 13%). Clinical benefit was observed in 12 of 22 patients (54%); PSA decline above 50% was observed in 11 patients (48%) and was associated with significantly longer overall survival. CONCLUSION: Our results indicate that Lu-PSMA is safe and active in elderly patients with mCRPC. IMPLICATIONS FOR PRACTICE: Lutetium-177-prostate-specific membrane antigen (Lu-PSMA), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen, enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer (mCRPC). The recently published single-arm phase II trial with Lu-PSMA, describing its safety and activity, did not include patients aged older than 75 years. In this study, Lu-PSMA activity was retrospectively analyzed in patients aged older than 75 years and results indicate that treatment was tolerable and similarly active in this age group, with no new emerging safety signals. Despite the small cohort size, this analysis suggests that Lu-PSMA can serve as an advanced palliative treatment line in mCRPC in elderly patients.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Idoso , Idoso de 80 Anos ou mais , Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Humanos , Lutécio , Masculino , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The most common cause of dementia is Alzheimer's disease. The major manifestation of the disease is the cognitive impairment which appears at the onset of the disease. In addition to the cognitive impairment there are behavioral dysfunctions such as apathy, anxiety, depression and sleep disturbances. The treatment for the manifestations of Alzheimer is currently pharmacological and behavioral. One of the newest behavioral treatments for Alzheimer is the multi-sensory treatment using the Snoezelen room. METHODS: The study group included 16 hospitalized Alzheimer patients. A device called the ActiGraph, which reads movement level, was placed on the subjects' non-dominant wrist. The measurements took place continually for five nights: two nights before snoezelen treatment, the day of treatment and two nights after the treatment. This protocol was repeated after a week of rest. RESULTS: The results showed that snoezelen treatment has a positive effect on the quality of sleep during the first week but not on the second week. CONCLUSIONS: Snoezelen treatment should be considered as part of the treatment regimen of Alzheimer patients, in addition to the pharmacological treatments in order to improve their quality of sleep and quality of life. Larger sample size and longer periods of time are needed to confirm the effectiveness of the treatment.
Assuntos
Doença de Alzheimer/fisiopatologia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Sono/fisiologia , Transtornos de Ansiedade/fisiopatologia , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
Immune checkpoint inhibitors (CPI) are indicated for metastatic renal cell carcinoma (mRCC). Immune-related thyroiditis (irT), an immune-related adverse event (irAE), affects up to 30% of patients. We aimed to determine whether irT is associated with overall survival in mRCC. A retrospective cohort study of 123 consecutive patients treated with CPI for mRCC in a single center between 2015 and 2020 was conducted. Disease risk stratification was assessed by two methods: Heng criteria and a novel dichotomic stratification system to "Low risk" versus "High risk" adding number of metastatic sites. Thirty-eight percent of patients developed irT. In the general cohort, irT was not associated with a survival benefit. However, irT was associated with better survival in the poor risk group per Heng criteria (n = 17, HR = 0.25, p = 0.04) and in the novel "High risk" group (HR = 0.28, n = 42, p = 0.01), including after accounting for covariates in multivariate analysis (HR = 0.27, p = 0.003). Having any irAE was associated with improved survival in the whole cohort, with no significant correlation of any specific irAE, in either the whole cohort or the "High risk" group. We conclude that irT is an early and prevalent irAE, associated with prolonged survival in patients with poor/"High" risk mRCC.
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Immunotherapy has transformed the landscape of treatment in metastatic renal cell carcinoma (mRCC) in the last decade. Currently, prognostic risk stratification is based on the model developed in the era of vascular endothelial growth factor receptor inhibitors (VEGFRi) by Heng in 2009. Our study aims to find the most relevant risk criteria for mRCC patients treated with checkpoint inhibitors (CPI). In a retrospective cohort study, laboratory, pathology, demographic, and clinical data were retrieved from electronic medical records of consecutive mRCC patients treated with CPI in a tertiary center between 2015 and 2020. An unbiased multivariate analysis was performed to define predictive variables with a bootstrap validation step. We analyzed data on 127 patients with a median follow-up of 60 months. The median overall survival (OS) since the diagnosis of metastatic disease was 57 months. The response rate for CPI was 39%. Five risk factors were correlated with worse OS: intact primary kidney tumor (HR 2.33, p = 0.012), liver metastasis (HR 3.33, p = 0.001),
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Immune checkpoint inhibitors (ICIs) are now the standard of care for metastatic urothelial carcinoma (mUC) patients. Our aim was to describe the activity of ICIs in mUC and find the clinical parameters associated with response. This is a retrospective, single-center chart review of mUC patients receiving ICIs. The overall survival (OS) was plotted using the Kaplan-Meier method and was compared using a log-rank test. Associations between the variables and responses were analyzed by univariate and multivariable analyses, using either logistic regression or a Chi-square/Fisher's exact test. Ninety-four patients received ICIs, 85% of which were in the second line or beyond; the median age was 71.8 years, and 82% were men. Six (6.4%), 11 (11.7%), 7 (7.4%) and 70 (74.5%) patients achieved a complete response (CR), partial response (PR), mixed response/stable disease (M/SD) or progressive disease (PD), respectively. The median overall survival was 3.2 months for the entire cohort and was significantly different according to the response pattern-not reached, 32.3, 6.4 and 2.0 months for CR, PR, M/SD and PD, respectively. The response was not significantly associated with the line of treatment. 'Site of metastasis' was associated with the response, and the absolute neutrophil count was borderline associated with the response. In summary, we found a substantial variance in the potential benefit from ICIs in mUC, emphasizing the need for predictive biomarkers and frequent monitoring of mUC patients receiving ICIs.
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Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan-Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or χ2/Fisher's exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of <0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline ≥20% and ≥50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline >20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the 'real-life' setting of heavily pretreated men with mCRPC.