Association between frailty and overall survival among older adults with hepatocellular carcinoma.

INTRODUCTION: Older adults undergoing cancer treatment often experience more treatment-related toxicities and increased risk of mortality compared to younger patients. The role of frailty among older individuals as a predictor of outcomes has gained growing significance. We evaluated the association between frailty and overall survival (OS) in patients with hepatocellular carcinoma (HCC) ≥60 years. MATERIALS AND METHODS: Older adults ≥60 years with HCC enrolled in a prospective single-institution registry underwent a patient-reported geriatric assessment (GA) covering multiple health domains related to prior to their initial medical oncology appointment. Frailty was measured using a 44-item deficit accumulation frailty index. We categorized patients as robust, pre-frail, and frail using standard cutpoints. The primary outcome was overall survival (OS). Univariable and multivariable models were built to evaluate the association between frailty and OS after adjusting for potential confounders. RESULTS: Total of 116 older adults with HCC with a median age of 67 years were enrolled; 82% male, 27% Black, and 78% with stage III/IV disease. Overall, 19 (16.3%) were robust, 39 (33.6%) pre-frail, and 58 (50.1%) frail. There were 76 patients receiving liver directed therapy. Of these, 13 (17%) were robust, 26 (34%) were pre-frail, and 37 (49%) were frail. Over a median follow up of 0.9 years, 53 patients died. After adjusting for age, stage, etiology, and Child-Pugh class, being frail (vs. robust) was associated with worse OS (hazard ratio (HR) 2.6 [95% CI 1.03-6.56]; p = 0.04). DISCUSSION: Half of the participants in this study were frail, which was independently associated with worse survival in adults ≥60 years of age with HCC. Identification of pre-treatment frailty may allow opportunities to guide treatment decisions and prognostication.

Tocilizumab in the treatment of steroid refractory immune-related hepatotoxicity: a case series and review of the literature.

With the widespread use of immune checkpoint inhibitors, management of immune-related adverse effects specific to these treatments became an important research era in patient management. Among these, immune-related hepatotoxicity (IRH) is an adverse event that can be fatal. While the first-line treatment of IRH is well established, there is still no consensus regarding the management approach for steroid-refractory, severe IRH. Here, we report four patients with metastatic melanoma who developed IRH during antiprogrammed cell death protein-1 plus anticytotoxic T-lymphocyte-associated protein-4 combination therapy and review of the literature. All of our patients were steroid-refractory and were successfully treated with tocilizumab. Given the rapid improvement in liver enzymes and patient's clinical status with tocilizumab, this treatment should be prioritized in steroid-refractory IRH.

Successful application of chemosaturation with percutaneous hepatic perfusion in metastatic uveal melanoma patient progressing after systemic treatment options: a case report.

Uveal melanoma (UM) is a rare subtype of melanoma, accounting for less than 5% of all melanoma cases. Metastatic UM differs notably from cutaneous melanoma, exhibiting variations in etiology, prognosis, driver mutations, metastatic patterns, and poor responses to immune checkpoint inhibitors (ICI). Beyond local treatment options, such as resection, radiation therapy, and enucleation, and systemic treatments, such as ICIs, the approval of tebentafusp, a bispecific gp100 peptide-HLA-directed CD3 T-cell engager, marks a breakthrough in treating HLA-A*02:01 metastatic UM. Despite the advancements in treatment options, the long-term survival rates remain inadequate. We report a patient with metastatic UM who previously received ICI and progressed on tebentafusp treatment but subsequently exhibited a remarkable response to local treatment targeting liver metastasis. Such observations highlight the significance of exploring sequential therapeutic strategies for advanced UM, offering potential avenues to enhance treatment efficacy and patient prognosis.

The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter real-world study from Turkey.

The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22-89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4-33.3) months, the median PFS and OS were 5.1 (95% CI: 3-7.3) and 18.1 (95% CI: 6.2-29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.

Management of Older Adults With Colorectal Cancer: The Role of Geriatric Assessment.

Older adults share a growing burden of cancer morbidity and mortality. This is present across the spectrum of oncologic diagnoses and is particularly true with colorectal cancer (CRC), where older adults continue to share the burden of diagnoses. However, optimal cancer treatment decision making in older adults remains a significant challenge, as the majority of previous clinical trials shaping the current treatment landscape have focused on younger patients, often with more robust performance status and fewer medical comorbid conditions. The heterogeneous aging process of older adults with CRC necessitates a personalized treatment approach, as approximately three-quarters of older adults with CRC also have a concominant geriatric syndrome and more than half of older adults with CRC are pre-frail or frail. Treatment decisions shoud be multifaceted, including consultation with the patient and their familes regarding their wishes, with consideration of the patient's quality of life, functional status, medical comorbid conditions, social support, and treatment toxicity risk. Geriatric assessment is a systematic and validated approach to assess an older adults's potential strengths and vulnerabilities, which can in turn be used to assist with comprehensive cancer care planning and support. In this review, we will summarize current treatment approaches for older adults with CRC, with a particular focus on the incorporation of the geriatric assessment.

Efficacy of local ablative therapies in patients with solid tumors treated with immune checkpoint inhibitors and oligoprogression: a single-center analysis.

The concept of oligoprogression reflects a situation where a limited number of metastatic tumor sites have progressed and other metastatic sites are under control with current systemic therapy. The optimal management of oligoprogression remains unclear. In this retrospective study, we evaluated the contribution of local ablative treatment approaches after oligoprogression to progression-free survival and response rates (RRs) in patients with renal cell carcinoma ( N : 5), nonsmall cell lung cancer ( N : 1) and melanoma ( N : 21) who received immunotherapy. We found that patients received local ablative therapies after oligoprogression had longer progression-free survival and higher RR compared to those who did not. Specifically, patients who received concurrent radiotherapy had a median survival time of 24.7 months compared to 14.5 months in those who did not. Our results suggest that local ablative therapies may have a beneficial impact on progression-free survival and RR in patients with oligoprogression who are being treated with immune checkpoint inhibitors. Further studies are needed to confirm these findings and determine the optimal use of local ablative therapies in this setting.