OBJECTIVE: Immune checkpoint inhibitors (ICIs) play an important role in the treatment of esophageal cancer (EC). However, few patients achieve long-term survival, and some patients develop serious immune-related adverse events (irAEs). Reliable predictive biomarkers of efficacy and safety need to be established in order to improve efficacy. We retrospectively analyzed the outcomes of nivolumab monotherapy on EC at Showa University, Department of Medicine, to identify biomarkers and characteristics of patients who benefit from ICI monotherapy.
METHODS: Eighty-six patients with EC who received nivolumab monotherapy were included in the present study. Patient characteristics, efficacy, and safety were analyzed. A multivariable analysis evaluated the correlation among overall survival (OS), progression-free survival (PFS), best overall response (BOR), irAEs, and the following variables: sex, age, performance status (PS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) level, albumin level, and body-mass index before treatment.
RESULTS: Median PFS was 3.1 months, and median OS was 9.0 months. In multivariable analysis, pretreatment PS, NLR, and sex were significantly correlated with OS and PFS. NLR <3.3 predicted longer survival (median OS 17.5 vs. 6.4 months for NLR ≥3.3; p<0.001). Median OS was 10.6 months for PS 0-1 and 1.3 months for PS 2-3 (p<0.001). NLR remained significantly predictive in the PS 0-1 group. The development of irAEs was significantly associated with increased OS and PFS.
CONCLUSIONS: Patients with low NLR and good PS before treatment may maximize the benefits of ICIs. A low NLR may be an indicator of higher immunocompetence for anti-tumor immunity, suggesting that NLR may be a convenient predictive biomarker in daily practice.

The efficacy of pembrolizumab in the treatment-naïve non-small-cell lung cancer (NSCLC) patients was proved in the KEYNOTE-024 randomized trial. The aim of this systematic literature review was to identify and summarize the real world evidence (RWE) of overall survival (OS) in previously untreated patients with NSCLC receiving pembrolizumab monotherapy. A systematic search was conducted in PubMed (MEDLINE®) and EMBASE databases. Analyses were focused on survival data (median OS and survival rates at specific time points). To explore the population comparable with the KEYNOTE-024 study, we focused on studies enrolling at least 50% of patients at stage IV of cancer and ECOG performance status 0-2. A total of 41 RWE studies covering over 7600 advanced NSCLC patients naïve to systemic treatment were identified. Overall, survival outcomes reported in those studies vary considerably (median OS range: 3.0-34.6 months). Most RWE studies reported median OS shorter to that reported in KEYNOTE-024 (26.3 months), but about half of reported OS medians were in range of 95% confidence interval for OS as reported in KEYNOTE-024 trial (18.3-40.4 months). Patients with similar characteristics of stage and performance status to those of KEYNOTE-024 trial benefited the same with pembrolizumab monotherapy as their survival outcomes (18.9-22.8 months) were consistent with those reported in the clinical trial. RWE data showed substantially worse outcomes in patients with ECOG-PS 2+ compared to ECOG-PS 0-1 patients.

BACKGROUND: Anamorelin is expected to improve cancer cachexia by increasing lean body mass (LBM) due to increased appetite and protein synthesis. However, the effect of anamorelin on cancer cachexia in real-world practice is unclear. The purpose of this study was to evaluate the efficacy and safety of anamorelin and to identify predictors of efficacy on treatment with anamorelin.
METHODS: We retrospectively analyzed data from patients with cancer cachexia treated with chemotherapy between May 2021 and August 2022. Efficacy of anamorelin was evaluated using LBM, with \"12-week sustained effective response\" to anamorelin treatment defined as maintenance or an increase in LBM for 12 weeks. We examined factors associated with \"12-week sustained effective response\" to anamorelin treatment using a multivariable logistic model that included controlling nutritional status (CONUT) score, an objective assessment of nutritional disorders, and the modified Glasgow prognostic score (mGPS), which scores the cachexia status of cancer patients. To assess patient subjective quality of life (QOL) changes related to eating after starting anamorelin treatment, we used a questionnaire (QOL-ACD appetite-related items: Q8, 9, 11). Adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
RESULTS: On analysis of data from 40 patients, 23 patients showed a 12-week sustained effective response to anamorelin (57.5%). At 12 weeks, LBM significantly increased by 1.63 ± 3.73 kg (mean ± SD). Multivariable logistic analysis revealed that a low CONUT score was significantly associated with \"12-week sustained effective response\" to anamorelin treatment (adjusted odds ratio: 13.5, 95% confidence intervals: 2.2-84.2, P = 0.004). QOL assessment showed a trend toward increased appetite and enjoyment of meals after anamorelin initiation. Five patients (12.5%) had an increase in HbA1c of more than 1.0% during the 12 weeks after the start of anamorelin. No patient had QT interval prolongation or grade 3 or higher hepatic transaminase elevation.
CONCLUSIONS: Anamorelin may maintain or increase LBM with tolerable safety in patients with cancer cachexia undergoing chemotherapy. A low CONUT score, despite meeting criteria for cancer cachexia, is suggested as a predictor for the efficacy of anamorelin, indicating that patients with a low CONUT score may benefit from early introduction of anamorelin.

OBJECTIVE: This study aimed to compare the postoperative outcomes of < 75-year-old patients and ≥ 75-year-old patients who underwent pancreaticoduodenectomy (PD) for pancreatic head and periampullary region tumors.
METHODS: Patients who underwent PD in our hospital between February 2019 and December 2023 were evaluated. Demographics, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores, American Society of Anesthesiologists (ASA) scores, comorbidities, hospital stays, complications, and clinicopathological features were analyzed. Patients were divided into < 75 years (Group A) and ≥ 75 years (Group B) groups and compared.
RESULTS: The median age of the entire cohort (n = 155) was 66 years (IQR = 16). There was a significant difference between Group A (n = 128) and Group B (n = 27) regarding the ECOG-PS and ASA scores. There was no significant difference between the groups regarding postoperative complications. The 30-day mortality rate was greater in Group B (p = 0.017). Group B had a cumulative median survival of 10 months, whereas Group A had a median survival of 28 months, with a statistically significant difference (p < 0.001). When age groups were stratified according to ECOG-PS, for ECOG-PS 2-3 Group A, survival was 15 months; for ECOG-PS 2-3 Group B, survival was eight months, and the difference was not statistically significant (p = 0.628).
CONCLUSIONS: With the increasing aging population, patient selection for PD should not be based solely on age. This study demonstrated that PD is safe for patients older than 75 years. In older patients, performance status and the optimization of comorbidities should be considered when deciding on a candidate\'s suitability for surgery.

UNASSIGNED: There is limited evidence regarding the feasibility of living-donor liver transplantation (LDLT) for patients aged over 70. The aims of this study were to assess postoperative outcomes in elderly recipients and to ascertain the potential feasibility and acceptability of LDLT.
UNASSIGNED: Data were collected from 762 recipients, including 26 in the elderly group (aged ≥70) and 736 in the younger group (aged <70), and reviewed even by propensity score matching (PSM).
UNASSIGNED: No significant differences were observed in the frequency of postoperative complications between the two groups. Additionally, both groups exhibited a comparable 30-day mortality rate after LDLT (3.9% in both) and similar hospital stays (36 days vs. 40 days). The 1-, 3-, and 5-year graft survival rates in the elderly group were 92.0%, which was comparable to those in the younger group (p = 0.517), as confirmed by PSM. Notably, all donors for elderly patients were the children of the recipients, with an average age of 41.6 years, and grafts from donors aged ≥50 years were not utilized, signifying the use of high-quality grafts. Our inclusion criterion for elderly recipients was strictly defined as an ECOG-PS score of 0-2, which played a pivotal role in achieving favorable postoperative outcomes.
UNASSIGNED: LDLT can be performed safely for elderly patients aged 70 years or older, provided they have a preserved PS and receive high-quality grafts from younger donors, inevitably all children of elderly recipients. This approach yields acceptable long-term outcomes. Consequently, age alone should not serve as an absolute contraindication for LDLT.

OBJECTIVE: In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown.
METHODS: Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy.
RESULTS: Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58).
CONCLUSIONS: Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.

Objective The efficacy of anamorelin in pancreatic cancer (PC) patients with a poor performance status (PS) is uncertain, as previous trials have excluded such patients. This study evaluated the efficacy of anamorelin in PC patients with a poor PS (2) compared with those with a good PS (0-1). Methods We retrospectively reviewed consecutive PC patients with cachexia who received anamorelin at our institution. The primary outcome was the proportion of responders, defined as those who maintained or gained body weight and appetite over 12 weeks. The secondary outcomes included anamorelin treatment duration, proportion of patients who discontinued anamorelin within 4 weeks (early discontinuation), and the overall survival. Results Forty-five patients (35/10) were included in this study. The proportion of responders was significantly lower in patients with a poor PS than in those with a good PS (0% vs. 37%, p=0.042). Moderate weight loss (5%-10%) and administration of pancreatic enzyme replacement therapy were associated with a response to anamorelin. A poor PS was significantly associated with a shorter treatment duration of anamorelin (14 vs. 93 days, p <0.001), a higher proportion of patients who discontinued anamorelin within 4 weeks (70% vs. 17%, p=0.003), and a reduced survival (62 vs. 188 days, p <0.001). A poor PS was associated with early discontinuation of anamorelin. Conclusions The efficacy of anamorelin is extremely limited in PC patients with a poor PS. Patients with PC with a poor PS may not be good candidates for anamorelin compared to those with a good PS.

BACKGROUND: The fast-track cancer pathway aims to expedite diagnosis of lung cancer and treatment and is the preferred route to diagnosis. Diagnosis following an unplanned admission (unplanned route) has been associated with poor outcomes.
OBJECTIVE: This study explores factors associated with lung cancer diagnosis following unplanned admissions, focusing on the elderly population.
METHODS: A retrospective cohort study using population-based data from Danish registries. Factors such as age, comorbidity, performance status, smoking history, socioeconomic parameters and treatment modality were analyzed in relation to route to diagnosis and prognosis.
RESULTS: Among 17,835 patients, 16% were elderly (≥ 80 years). The unplanned route constituted 28% of diagnostic routes, with higher proportion among the elderly (33%). Poor performance status and advanced disease stage were associated with the unplanned route. Married patients were less likely to undergo an unplanned route to diagnosis. Smoking did not significantly influence diagnostic route. The adjusted odds ratio for curative treatment and dying 12 months after diagnosis, following unplanned route to diagnosis were 0.68 (95% CI, 0.61-0.76) and 1.48 (95% CI, 1.36-1.61), respectively.
CONCLUSIONS: Frailty (poor performance status and high burden of comorbidity) in addition to unfavorable socioeconomic factors, which all were more prevalent among elderly patients, were associated with undergoing an unplanned route to diagnosis. However, age itself was not. Diagnosis following unplanned admission correlated with reduced likelihood of curative treatment and poorer prognosis. Expanding screening initiatives to include frail elderly individuals living alone, along with alertness by primary care clinicians, is warranted to improve outcomes for these patients.

OBJECTIVE: Performance status is an important concept in oncology, but is typically clinician-reported. Efforts are underway to include patient-reported measures in cancer care, which may improve patient symptoms, quality of life and overall survival. The purpose of this study was to gain a preliminary understanding of how patients determined their physical performance status based on a novel patient-reported version of the Eastern Cooperative Oncology Group Performance Status (ECOG) scale.
METHODS: We conducted qualitative interviews, including concept elicitation and cognitive interviewing as part of the Patient Reports of Physical Functioning Study (PROPS) to investigate how participants selected their answers to a novel patient-reported ECOG. Participants were administered the patient-reported ECOG and asked to describe devices and modifications used to keep up with daily activities.
RESULTS: Participants generally understood the ECOG as intended. Participants with recent changes in status had some difficulty selecting an answer. Most participants used modifications and assistive devices in their daily lives but did not incorporate these into their rational for the ECOG.
CONCLUSIONS: The potential benefits of a patient-reported ECOG are numerous and this study demonstrates that participants were able to understand and answer the patient-reported ECOG as intended. We recommend future evaluation for the most-appropriate recall period, whether to include modifications in the ECOG instructions, and if increasing the number of response options to the patient-reported ECOG may improve confidence when providing an answer.

Neurological disorders are one of the leading causes of disability globally. Studies emphasise that the course and effectiveness of rehabilitation interventions may be influenced by emotional factors. The aim of the present study was to assess the prevalence of depressive and anxiety symptoms in patients with neurological disorders and examine whether depression and tendency to respond with anxiety are predictors of disability in these patients. The study included 229 individuals with neurological disorders aged over 55. Our findings show that stroke patients are more likely to experience depressive symptoms and are more likely to display trait anxiety as compared with patients with other neurological disorders. Advanced age, female sex, low level of education and the presence of trait anxiety are associated with a higher severity of depressive symptoms. Stroke survivors have significantly poorer ECOG performance scores and are more likely to be incapable for work. Both depression and trait anxiety are significant predictors of neurological patients\' performance status, and the presence of depressive symptoms is a determinant of these patients\' level of satisfaction with life. An understanding of psychological risk factors for poorer performance status in individuals with neurological disorders will make it possible to plan prophylactic interventions in order to minimise negative health impacts and facilitate access to mental health facilities.