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OBJECTIVE: Post-ICU survivors face higher mortality and often require costly rehabilitation or palliative care, such as occupational therapy, physiotherapy and hospice. However, there is a lack of data quantifying the demand for these services, particularly in developing countries like Uganda. Therefore, this prospective cohort study aimed to investigate the 90-day mortality rate, functional status, and mortality risk factors among 121 ICU patients discharged from three tertiary hospital ICUs in Uganda by tracking their vital and physical functional status for three months with follow-ups on days 30, 60, and 90, and identifying risk factors through Cox regression. RESULTS: The study revealed that 18 out of 121 ICU patients (14.88%, 95% CI: 9.52-22.51%) died within 90 days post-discharge, while 36.36% achieved normal physical functional status. Factors associated with higher 90-day mortality included raised intracranial pressure (HR 1.92, 95% CI: 1.76-2.79, p = 0.04), acute kidney injury (HR 4.13, 95% CI: 2.16-7.89, p < 0.01), and renal replacement therapy (HR 3.34, 95% CI: 2.21-5.06, p < 0.01). The high mortality rate and the fact that nearly two-thirds of patients did not attain normal functional status 90 days post discharge underscores the need for enhanced post-ICU rehabilitation services.
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Unidades de Terapia Intensiva , Sobreviventes , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Feminino , Estudos Prospectivos , Uganda/epidemiologia , Pessoa de Meia-Idade , Adulto , Sobreviventes/estatística & dados numéricos , Fatores de Risco , Países em Desenvolvimento/estatística & dados numéricos , Pobreza , IdosoRESUMO
BACKGROUND: The simplified Pulmonary Embolism Severity Index (sPESI) has limitations when evaluating acute pulmonary embolism (PE) in patients with concurrent malignancy. Despite its utility in predicting outcomes among cancer patients, the role of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in acute PE remains underexplored. This study aims to assess the prognostic significance of ECOG PS ≥ 3 on short- and long-term mortality in acute PE with malignancy, correlating it with the sPESI. METHODS AND RESULTS: We retrospectively analyzed 44 hemodynamically stable acute PE patients with unresectable or metastatic malignancies ineligible for curative treatment at Kameda Medical Center, a tertiary medical facility in Japan, from April 1, 2019, to March 2, 2023. Of these patients, 16 (36.4%) had ECOG PS ≥ 3. No 30-day mortality occurred in patients with ECOG PS ≤ 2, compared to 18.8% in those with ECOG PS ≥ 3 (p = 0.04). Groups were similar in the sPESI scores, hospital-onset PE proportion, and initial treatments. Post PE diagnosis, 92.9% of ECOG PS ≤ 2 patients and 50% of ECOG PS ≥ 3 patients received chemotherapy (p = 0.002). Cox regression analysis revealed ECOG PS ≥ 3 was independently associated with increased overall survival hazard (adjusted HR = 4.0; P = 0.002). CONCLUSIONS: ECOG PS ≥ 3 suggests a poorer short-term prognosis and independently predicts a worse long-term prognosis in hemodynamically stable acute PE patients with advanced malignancies.
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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.
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Neoplasias Pancreáticas , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Pancreaticoduodenectomia/métodos , Idoso , Masculino , Feminino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Idoso de 80 Anos ou mais , Fatores Etários , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: The efficacy, safety, and liver toxicity of enfortumab vedotin (EV) for elderly advanced urothelial carcinoma (UC) patients and patients with a poor performance status (PS) are unclear. PATIENTS AND METHODS: We retrospectively analyzed the efficacy, safety, and liver toxicity of EV in elderly patients and patients with a poor PS between December 2021 and August 2023. RESULTS: Sixty-two patients (≥75 years old, n=22; PS≥2, n=10) were enrolled. Patients with PS≥2 had significantly lower albumin levels than those with PS<2 (p=0.023). The objective response and disease control rates did not differ significantly between patients <75 and ≥75 years old (p=0.598 and p=0.769, respectively) or between those with PS<2 and PS≥2 (p>0.99 and p=0.178, respectively). Progression-free survival (PFS) and overall survival (OS) were not significantly different in patients <75 years and ≥75 years (p=0984, 0.368). A significant difference in PFS (p=0.047) but not OS (p=0.086) was observed between the PS<2 and PS≥2 groups. The rates of any-grade and severe (grade ≥3) adverse events did not differ significantly between patients <75 and ≥75 years (p=0.471, p=0.136) or between PS<2 and PS≥2 groups (p>0.99, 0.99). Aspartate aminotransferase (AST) levels significantly increased, but alanine aminotransferase levels did not, following EV treatment (p<0.001). Multivariate analyses revealed that the albumin level was an independent prognostic factor (hazard ratio=0.159; p<0.001). CONCLUSION: EV demonstrated similar efficacy and safety in elderly and younger patients with advanced UC. In patients with a poor PS, although the safety was similar, survival was significantly worse in terms of PFS, while the AST levels were significantly elevated.
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Anticorpos Monoclonais , Humanos , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/mortalidade , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/mortalidade , Intervalo Livre de Progressão , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND/AIM: 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. PATIENTS AND 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. CONCLUSION: 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.
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Neoplasias Esofágicas , Inibidores de Checkpoint Imunológico , Linfócitos , Neutrófilos , Humanos , Masculino , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neutrófilos/imunologia , Idoso , Pessoa de Meia-Idade , Linfócitos/imunologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Adulto , Contagem de Linfócitos , Resultado do Tratamento , Intervalo Livre de ProgressãoRESUMO
PURPOSE: 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). CONCLUSION: 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.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Feminino , Idoso , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Fragilidade , Idoso de 80 Anos ou maisRESUMO
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. CONCLUSION: 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.
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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.
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Aim: 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. Methods: 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). Results: 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. Conclusion: 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.
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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.
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Background: There is a lack of readily available clinical markers of non-small cell lung cancer (NSCLC) immunotherapy efficacy. Previous studies have found that overexpressed complement component 1q (C1q) promotes macrophage M2 polarization and an immunosuppressive tumor microenvironment. This study aimed to evaluate the association between serum C1q and the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC. Methods: A total of 168 patients with advanced NSCLC who received ICIs in the Renmin Hospital of Wuhan University were included in this study. Serum C1q levels were collected before and 3 weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. The primary outcome was overall survival (OS) (months from first dose of ICIs to death, censored at date of last follow-up). Secondary outcome was progression-free survival (PFS) [defined as months from first dose of ICIs to clinical or radiographic progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death, censored at date of last follow-up] and objective response rate (ORR) which was defined as rate of complete response (CR) or partial response (PR) at best response by RECIST 1.1. Results: A total of 168 patients were included in this study, including 127 males (75.60%) and 41 females (24.40%). Thirty-nine patients achieved objective response (2 CR, 37 PR), and 111 patients (66.07%) had stable disease (SD) as best response. The ORR was 23.21% and the disease control rate was 89.28%. The upward trends of serum C1q levels between baseline and post-treatment were strongly associated with the shorter PFS [hazard ratio (HR) =1.554, 95% confidence interval (CI): 1.07-2.10, P=0.01] and OS (HR =1.444, 95% CI: 1.01-1.98, P=0.03). Moreover, taking the median OS 18.9 months as the cut-off of prognosis, receiver operating characteristic (ROC) analysis showed that serum baseline C1q yielded an area under the ROC curve of 0.785 (95% CI: 0.711-0.869). The optimal serum baseline C1q cut-off point to predict immunotherapy prognosis was 216.2 mg/L. Conclusions: These findings suggested that elevated serum C1q after ICIs treatment was related to a worse prognosis in NSCLC. Monitoring the baseline and dynamic data of C1q during hospitalization showed the potential to predict the prognosis of NSCLC patients.
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AIM: An accurate assessment of the general condition of patients with hepatocellular carcinoma (HCC) is essential. We evaluated the impact of grip strength (GS) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) on the clinical outcomes of patients with unresectable HCC (u-HCC) treated with atezolizumab plus bevacizumab. METHODS: This observational cohort study analyzed 89 patients with u-HCC treated with atezolizumab plus bevacizumab between October, 2020 and October, 2023. A Cox proportional hazards model and Kaplan-Meier curve were used to identify the prognostic factors associated with survival outcomes. RESULTS: There were 33 patients who had low GS and 16 had an ECOG-PS ≥1. The frequency of patients with low GS increased as the ECOG-PS score increased. The overall survival of the normal GS group was significantly higher than that of the low GS group (p < 0.01). There was no significant difference in progression-free survival between the normal GS group and low-GS group (p = 0.28). Among the patients in the ECOG-PS 0 groups, the overall survival in the normal GS group was significantly higher than that in the low GS group (p < 0.01). A multivariate analysis revealed that modified albumin-bilirubin 2b (HR 2.24; 95% confidence interval [CI] 1.06-4.73), α-fetoprotein ≥100 ng/mL (HR 2.35; 95% CI 1.20-4.58), and low GS (HR 2.87; 95% CI 1.31-6.27) were independently associated with a poor overall survival. CONCLUSIONS: The present study demonstrated that GS is a sensitive marker for detecting a subclinical decline in the general condition and is therefore a potential predictor of the outcome of u-HCC patients treated with atezolizumab plus bevacizumab.
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PURPOSE: 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. CONCLUSION: 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.
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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. CONCLUSION: 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.
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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.
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Key Clinical Message: One Kirsten Ras (KRAS) G12C mutated non-small cell lung cancer (NSCLC) patient had improved poor performance status and obtained mixed response with the first-line KRAS-targeted treatment of sotorasib. After disease progression, partial response was achieved with chemotherapy plus immunotherapy. KRAS G12C mutated immunoenvironment in NSCLC may favor the immunotherapy. Abstract: KRAS is one of the most commonly mutated genes, which used to be untargetable. The phase II CodeBreak 100 trial revealed 6.8-month median progress-free survival (PFS) and 12.5-month overall survival (OS) in previously treated KRAS G12C-mutant NSCLC patients treated with KRAS inhibitor, sotorasib. The specimens of the brain, lymph node (LN), and blood from the patient were analyzed by next-generation sequencing. Hematoxylin and eosin staining and immunohistochemistry were performed for pathological characterization. Computed tomography (CT) and magnetic resonance imaging (MRI) scan were used for treatment response evaluation. The patient was diagnosed in a bad Eastern Cooperative Oncology Group performance status (ECOG-PS) with metastatic KRAS G12C-mutated lung adenocarcinoma who had achieved mixed response to sotorasib as the first-line treatment. Although 5-month PFS of the treatment with sotorasib was not surprising, the patient achieved significantly improved ECOG-PS score from 4 to 1. Subsequently, partial response (PR) was achieved with the treatment of pemetrexed plus pembrolizumab. This case highlights superior efficacy of first-line treatment with sotorasib for the advance untreated KRAS G12C-mutant patients. The high efficacy of the treatment with chemotherapy plus immunotherapy revealed that immunoenvironment of KRAS G12C-mutated patient may favor the immunotherapy.
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BACKGROUND AND OBJECTIVES: OSA is a known medical condition that is associated with several comorbidities and affect patients' quality of life. The association between OSA and lung cancer remains debated. Some studies reported increased prevalence of OSA in patients with lung cancer. We aimed to assess predictors of moderate-to-severe OSA in patients with lung cancer. METHODS: We enrolled 153 adult patients who were newly diagnosed with lung cancer. Cardiorespiratory monitoring was performed using home sleep apnea device. We carried out Univariate and multivariate logistic regression analysis on multiple parameters including age, gender, smoking status, neck circumference, waist circumference, BMI, stage and histopathology of lung cancer, presence of superior vena cava obstruction, and performance status to find out the factors that are independently associated with a diagnosis of moderate-to-severe OSA. RESULTS: Our results suggest that poor performance status is the most significant predictor of moderate to severe OSA in patients with lung cancer after controlling for important confounders. CONCLUSION: Performance status is a predictor of moderate to severe OSA in patients with lung cancer in our population of middle eastern ethnicity.
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Neoplasias Pulmonares , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Pessoa de Meia-Idade , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/diagnóstico , Idoso , Valor Preditivo dos Testes , Adulto , Fatores de Risco , Polissonografia/métodosRESUMO
CONTEXT: Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs. OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC. METHODS: The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data. RESULTS: Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia. CONCLUSIONS: Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Medicina Tradicional Chinesa , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Resultado do TratamentoRESUMO
Background: Generalizability of registrative clinical trials to real-world clinical practice is influenced by comparability of patients in the two settings. We compared characteristics of cancer patients in registrative trials with real-world clinical practice in Italy. Methods: Data on age, sex and performance status (PS) were derived from web-based monitoring registries developed by Italian Medicines Agency (AIFA) and corresponding registrative trials reported in the European Public Assessment Reports (EPAR) of European Medicines Agency (EMA). Weighted means were calculated in registries and trials and differences were described. Multivariate analysis was performed using Principal Component Analysis and Cluster Analysis. Findings: From January, 2013 to April, 2023, 419,461 unique pairs of patients and therapeutic indications were recorded in 129 AIFA registries. Within 140 related trials, 87,452 patients had been enrolled. Median age and rate of elderly (≥65 years old) patients were higher in monitoring registries than in clinical trials [mean difference of median age 5.3 years, p < 0.001; mean difference of elderly rate 17.17% (95% CI 1.06, 1.48)]. Overall, rate of female patients was not different between registries and trials [mean difference -0.55% (95% CI -1.06, -0.05)]. Mean rate of patients with deteriorated PS was low both in trials (3.1%) and in registries (4.3%) with a mean difference of 1.27% (95% CI 1.06, 1.48). Two clusters were identified with multivariate analysis: one including more registries (higher median age and elderly rate, lower female rate, higher rate of deteriorated patients), the other more trials (lower median age and elderly rate, higher female rate, lower rate of deteriorated patients). Interpretation: This study supports that cancer patients enrolled in trials do only partially represent those who have been treated in Italy in clinical practice. Inclusiveness of registrative trials should be increased to ensure generalizability of results to real-world population. Funding: Partially supported by Italian Ministry of Health.
RESUMO
BACKGROUND: There is no consensus on the second-line treatment of patients with progressive high-grade neuroendocrine neoplasms (NENs G3) and large-cell lung neuroendocrine carcinoma. These patients generally have poor performance status and low tolerance to combination therapy. In this trial, we aim to evaluate the efficacy and safety of temozolomide given every other week in patients with advanced platinum-pretreated NENs G3. PATIENTS AND METHODS: This trial is an open-label, non-randomized, phase II trial. Patients with platinum-pretreated metastatic neuroendocrine carcinoma were treated with 75 mg/m2/day of temozolomide for 7 days, followed by 7 days of no treatment (regimen one week on/one week off). The primary endpoint was the overall response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and tolerability. This study is registered with ClinicalTrials.gov, NCT04122911. RESULTS: From 2017 to 2020, 38 patients were enrolled. Among the patients with determined Ki67, 12 out of 36 (33.3%) had a Ki67 index <55% and the remaining 24 out of 36 (66.6%) had an index ≥55%. Overall response rate was 18% (7/38), including one complete response and six partial responses. The median PFS was 5.86 months [95% confidence interval (CI) 4.8 months-not applicable) and the median OS was 12.1 months (95% CI 5.6-20.4 months). The 1-year PFS rate was 37%. No statistically significant difference in median PFS [hazard ratio 1.3 (95% CI 0.6-2.8); P = 0.44] and median OS [hazard ratio 1.1 (95% CI 0.5-2.4); P = 0.77] was observed among patients with Ki67 <55% versus ≥55%. Only G1-G2 adverse events were registered, the most common being G1 nausea, diarrhea and abdominal pain. CONCLUSION: One week on/one week off temozolomide shows promising activity in patients with poorly differentiated NEN. The good safety profile confirmed the possibility of using this scheme in patients with poor performance status.