Higher Eastern Cooperative Oncology Group Research Articles

Combination anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report.

Up to 80% of biliary tract cancer (BTC) patients relapse within 3 years after surgery and the efficacy of second-line treatment remains dismal for patients who progressed on gemcitabine and cisplatin chemotherapy. Median overall survival of patients with palliative chemotherapy is less than 1 year. The feasibility and safety of targeted therapies plus immunotherapies remain scanty currently, and patients with recurrent or advanced BTCs often experience a rapid decline in Eastern Cooperative Oncology Group (ECOG) performance status. This case report is the first report suggesting a 17-month progression-free survival (PFS), partial response, and another 11-month PFS after progressive disease of anlotinib plus toripalimab in advanced BTC with high ECOG performance status. We report a 67-year-old Chinese male with BTC. He was observed with progressive disease after surgical resection, adjuvant chemotherapy, palliative chemotherapy, and diagnosed with American Joint Committee on Cancer clinical stage IV (cT3N0M1) extrahepatic BTC. The patient experienced a rapid decline in performance status, and he received oral anlotinib and toripalimab with informed consent. MRI scans showed partial response on 22 June 2022. PET-CT showed that tumor activity has been inhibited on 8 March 2023. He achieved 17 months of PFS. Although the patient developed solitary lung metastasis, he had a continuous survival benefit from treatment of anlotinib plus toripalimab after lung radiotherapy. Until the writing of the case draft, he had achieved another 11 months of PFS. The present case suggests that anlotinib plus toripalimab might be a potential effective treatment for advanced BTCs patients with high ECOG performance status.

Lymphoma relapse 1 year or later after immunochemotherapy in DLBCL patients: clinical features and outcome

Despite great advances in treatment, 30–40% of patients with DLBCL undergo relapses. Patients with a relapse within 1 year or beyond have a distinct outcome. Few clinical characteristics and survival data in the Chinese population have been published. We aimed to define the incidence and clinical features of DLBCL patients with very early relapse after front-line immunochemotherapy who may benefit greatly from the emerging chimeric antigen receptor T-cell therapy. Data of 564 DLBCL patients were analyzed. Among the 413 patients achieving a first complete remission, 59 underwent relapses: 32 patients (54.2%) relapsed within 1 year, and 27 patients (46.8%) relapsed 1 year or more. Patients relapsing within 1 year, in comparison with the other group, showed an inferior risk profile at diagnosis: elevated lactate dehydrogenase level (P = 0.002), high Eastern Cooperative Oncology Group performance score (P = 0.02), and high international prognosis index (P = 0.004). As expected, a worse overall survival was observed in the early relapse group. Multivariate analysis for OS showed that relapse within 1 year was an independent parameter for reduced overall survival (HR 0.241, P = 0.002).

Real-World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients.

This study aims to describe the overall survival (OS) and to identify associated prognostic factors in patients with inoperable and metastatic cutaneous melanoma of the head and neck (H&N) region, undergoing modern systemic treatments. This is a retrospective single institutional study. Data on all consecutive H&N melanoma patients treated with systemic oncologic treatments between 2015 and 2022 were collected from electronic medical files. Kaplan-Meier curves were used to describe survival and Cox regression analysis was used to identify patient and tumor factors associated with prognosis. A total of 144 patients were included. Median OS was 45 months (95% confidence interval [CI] 28-65 m). On univariable analysis for OS, the primary disease site, specifically the nape and neck (hazard ratio [HR] 3.3, 95% CI 1.4-7.7, p = 0.007), high Eastern Cooperative Oncology Group Performance Status ([ECOG-PS], HR 2.5, 95% CI = 1.9-3.3, p < 0.001), high lactate dehydrogenase (LDH) levels (HR 2.8, 95% CI = 1.7-4.6, p < 0.001), and treatment with targeted therapy (TT) as compared with immunotherapy (HR 2.6, 95% CI = 1.06-6.3, p = 0.03) were all associated with shorter OS. High-grade adverse events (AEs) were associated with a longer OS (HR 0.41, 95% CI = 0.25-0.68, p = 0.001). On multivariable analysis for OS, the ECOG-PS, LDH levels, site of disease, and the development of moderate-severe AEs remained significant. In the era of modern oncologic treatments, the prognosis of inoperable and metastatic cutaneous H&N melanoma aligns with other cutaneous melanomas. Primary tumor site of the nape and neck region emerges as a significant prognostic factor. 3 Laryngoscope, 134:2762-2770, 2024.

Incidence and Predictors of Venous Thromboembolism and Mortality in Saudi Lung Cancer Patients: A Retrospective Two-center Cohort Study

BACKGROUND: Venous thromboembolism (VTE) frequently occurs among individuals with cancer, and lung cancer (LC) is among the malignancies associated with the highest rate of VTE development. PURPOSE: The study’s objective was to ascertain the incidence rates of VTE and evaluate predictors of both VTE occurrence and mortality in LC patients. METHODS: This two-center retrospective study involved 497 Saudi Arabian patients diagnosed with LC aged ≥ 18 years. In this study, we calculated VTE incidence and mortality rates. We conducted Cox regression analyses (both univariate and multivariate) to explore the relationship between patient characteristics, VTE, and mortality using a 95% confidence interval (CI) and hazard ratios (HRs). RESULTS: Among 497 LC patients, 98 developed VTE, resulting in a prevalence rate of 9.8 per 100 person-years (PYs) with a 95% CI of 8.0–11.8. Furthermore, 280 patients passed away, resulting in a mortality rate of 26.5 per 100 PY with a 95% CI of 23.9–29.3. Low albumin levels, diagnosis of nonsmall cell LC (NSCLC), and high Eastern Cooperative Oncology Group (ECOG) performance status were all independent risk factors for VTE. Patients with VTE had notably higher mortality risk (HR: 3.10; 95% CI, 2.53–3.91; P &lt; 0.001) than non-VTE patients. The Kaplan–Meier analyses showed that the predicted median time of VTE occurrence was significantly higher in small cell LC (SCLC) (33.7 months) (P = 0.002 by the log-rank test) compared to NSCLC (28.7 months) patients. Furthermore, the estimated median time of survival for NSCLC patients (23.8 months) was significantly lower than in SCLC (29.7 months) (P &lt; 0.001 by the log-rank test). CONCLUSION: The study findings indicated that the VTE occurrence in LC patients was 9.8 per 100 PY, with a corresponding mortality rate of 26.5 per 100 PY. Reduced levels of albumin, ECOG performance status, and NSCLC emerged as significant risk factors of VTE. Patients who experienced VTE had a 3.10-fold higher mortality risk than non-VTE LC patients.

Cardiac Morbidity and Mortality in Patients with Sarcoma: A Population-Based Study.

Soft tissue sarcoma (STS) is a rare malignancy that affects soft tissues. It encompasses various subtypes and requires different treatment strategies. Doxorubicin is a commonly used anthracycline in the management of localized and metastatic STS. However, high doses of doxorubicin are associated with cardiotoxicity, which can significantly impact patients' long-term outcomes. This study aimed to evaluate doxorubicin's effect on cardiac function in patients with sarcoma and to correlate the frequency of cardiotoxicity with potential risk factors. A retrospective analysis was conducted on patients with sarcoma who were treated with doxorubicin between 2016 and 2022 at King Abdulaziz Medical City in Saudi Arabia. Patient demographic information, comorbidities, cardiac measurements, laboratory values, systemic therapy, and treatment outcomes were collected from electronic medical records. A statistical analysis was performed to assess the association between cardiotoxicity and various factors. A total of 133 patients were included in the study, with a median age of 30 years. Cardiotoxicity was observed in 9% of the patients. Female patients had a significantly higher risk of developing cardiotoxicity. Patients with a higher Eastern Cooperative Oncology Group (ECOG) performance status and lower troponin I levels also had an increased risk of cardiotoxicity. However, there was no significant association between cardiotoxicity and the number of chemotherapy cycles, total cumulative dose of doxorubicin, or history of radiation. Furthermore, patients with cardiotoxicity had a higher risk of mortality. The overall survival of the patients was 18 months. Doxorubicin-associated cardiotoxicity is a concern for patients with sarcoma. Female patients and patients with a higher ECOG performance status are at an increased risk of developing cardiotoxicity. Careful monitoring and risk assessment are crucial for mitigating the adverse effects of doxorubicin treatment in patients with sarcoma. Future studies are warranted to validate these findings and explore preventive strategies for doxorubicin-induced cardiotoxicity in patients with sarcoma.

Frail and Pre-Frail Older Adults with Acute Myeloid Leukemia Have Inferior Survival Due to Higher Rates of Disease-Related Deaths

Introduction: The intensity of initial remission-inducing therapy for patients with newly diagnosed acute myeloid leukemia (AML) may be high (anthracycline and cytarabine-based), intermediate (venetoclax combinations), or low (single hypomethylating agent or targeted therapy). In older adults, it is important to consider “fitness” when selecting initial therapy. Current methods to determine “fitness” in AML include subjective measures such as physician assessment (“clinician gestalt, CG”) semi-subjective measures such Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status (KPS), and those based on clinical comorbidity data like the hematopoietic cell transplantation-comorbidity index (HCT-CI). Geriatric assessments in older adults with cancer may improve therapy selection and decision-making, but whether unfit patients have better outcomes with lower intensity compared to higher intensity therapies is unknown. Freid's Frailty Phenotype (FP) combines subjective (self-reported exhaustion, weight loss &amp;gt;5%, activity level) and objective (4-meter walk speed and grip strength) measures to categorize patients into fit, pre-frail, and frail. We hypothesized that being frail by FP is associated with higher overall mortality (OM) and inferior overall survival (OS) and may inform decision-making for older adults. Methods: Eighty-fivepatients 60 years or older admitted to the Hospital of the University of Pennsylvania at the time of AML diagnosis or electively admitted for AML chemotherapy initiation were prospectively enrolled from September, 2018 to May, 2023 on an IRB approved study. FP, HCT-CI, KPS, ECOG, gait speed, and recorded CG (fit or unfit) were performed prior to initiation of disease-directed therapy. Results: Themedian age of the cohort was 71 (range60-91). Patients in our cohort had high-risk disease features: 64% were adverse risk by European LeukemiaNet (ELN) 2017 with 73% of patients harboring mutations associated with clonal hematopoiesis of indeterminate potential (CHIP) (Table 1). 39% of patients received IC, 52% received HMA/ven, 6% received HMA alone or targeted therapy, and 2% received best supportive care. By FP, 18% of patients were fit, 38% were pre-frail, and 45% were frail. Higher ECOG, KPS, CG, and HCT-CI were associated with frail phenotypes (Table 1). For the entire population, 60-day and 100-day OM rates were 18% and 33%, respectively. For fit, pre-frail, and frail patients 60-day OM was 7%, 13%, and 24% and 100-day OM was 13%, 22%, and 42%, respectively. Two-year OS was 65% for patients aged 60-69 years old and 15% for patients ≥70 years old (p=0.002). FP was significantly associated with OS (Figure 1; p=0.0474): 2-year OS was 57%, 42%, and 21% in fit, pre-frail, and frail patients, respectively. Of the individual components of FP, self-reported exhaustion and slower gait speed were both associated with inferior OS (p=0.0015 and p=0.0005). Neither activity level, (p=.0864), weight loss (p=0.1988), or grip strength (p= 0.7136) were associated with OS. Of the total population 19% went on to hematopoietic cell transplant (HCT) with 8% of frail patients receiving HCT compared to 27% of fit and 28% of pre-frail patients. ECOG, HCT-CI, CG, and gait speed ≤8 meters/sec were all significantly associated with OS, but KPS was not. The 6-month OS for frail patients receiving IC was 75% compared with 49.7% for those receiving HMA/Ven, although not significant due to small sample size. Cause of death was leukemia-related for 40% of fit patients, 76% of pre-frail patients, 77% of frail patients. Conclusions: FP was associated with a doubling of early mortality and inferior 2-year OS. Pre-frail and frail patients had increased disease-related deaths. This work supports that most geriatric assessments, including FP and clinician intuition, can be utilized to risk-stratify newly diagnosed older adults with AML. Future work is needed to evaluate whether we can integrate geriatric assessments, such as individual components of FP or gait speed, with molecular features to improve risk stratification of older adults with AML. Given frailty's association with disease-related deaths, further study is warranted to determine whether this is due to adverse disease biology or whether frail patients are undertreated.

Profound impact of ECOG performance status on clinical trial eligibility and access: Diverging effects by cancer type.

97 Background: The Eastern Cooperative Oncology Group (ECOG) performance status is a widely used measure of a patient's (pt) physical function and is often used as a criterion for clinical trial eligibility. Strict use of this criterion may exclude pts with comorbidities or poorer performance status, limiting the generalizability of trial results to the broader cancer pt population. This study aimed to evaluate the impact of ECOG performance status on eligibility for solid and non-solid cancer clinical trials (CTs) among pts using the Leal web-based platform. Methods: Leal (formerly, Trialjectory) is an AI-based platform that matches cancer pts to CTs based on a self-reported questionnaire that generates an individual clinical profile. The profile includes parameters essential for CT matching such as disease status, stage, biomarkers, treatment history, comorbidities and demographics. Data from pts with solid and non-solid cancers were analyzed. The number of matched trials per pt was determined based on the pt’s profile, location and travel preference. To assess the impact of ECOG score, the data set was edited to reflect a better performance status per pt. We used Yuen’s robust paired samples analysis to assess the association between improving the ECOG score and the number of matched CTs. Moreover, we have collected the cumulative ECOG distribution as an eligibility criteria in CTs in various cancer types. Results: In a data set of 5,018 cancer pts, high ECOG score (3 or 2) was significantly associated with fewer matched clinical trials per pt (p&lt;0.001). This relationship was independent of ethnicity and gender. The relationship varied by cancer type, with a 3-fold greater effect size in solid tumors compared to non-solid tumors. When ECOG score per pt was edited from 3 to 2 or from 2 to 1, the number of matched CTs significantly increased by 246% and 189%, respectively, for all cancer types (p&lt;0.001). Notably, the prevalence of CTs that allow worse ECOG scores (2 or higher) was significantly higher in non-solid CTs compared to solid tumors (p&lt;0.001). Conclusions: Our results show that strict ECOG scores are significantly associated with fewer matched CTs per pt. This relationship varies by cancer type, with a greater impact on solid tumors. These findings suggest that cancer type may influence the relationship between ECOG scores and access to CTs. Pts with solid tumors may face more barriers to trial enrollment due to strict ECOG requirements. Our results highlight the need for a more nuanced approach to using ECOG performance status as an eligibility criterion in CTs, taking into account the specific cancer type and its associated physical demands. Further research is needed to fully understand the impact of ECOG performance status on trial enrollment and to determine the optimal balance between pt safety and representation in clinical research.

Predictive factors for the success of trial without catheter for men with urinary retention.

To investigate the trial of spontaneous urination without catheter (TWOC) outcomes for men with acute urinary retention, determine successful TWOC predictors, and evaluate the impact of add-on medication therapy on TWOC. This retrospective study included men with acute urinary retention and post-void residual (PVR) >250 mL who underwent TWOC between July 2009 and July 2019. Patients were divided into a medicated group who received alpha1 blocker on urinary retention diagnosis and a naïve group who did not. The trial was defined as unsuccessful if the PVR was >150 mL or if the patient experienced difficulty emptying their bladder with abdominal discomfort or pain, and a transurethral catheter was reinserted. Among 576 men with urinary retention, 269 (46.7%) constituted the medicated group and 307 (53.3%) the naïve. The naïve group comprised more elderly patients (P = 0.010) with higher Eastern Cooperative Oncology Group performance status (PS) (P = 0.001) and smaller prostate volume (P = 0.028) than the other. In the medicated group, 153 men received additional oral medication before TWOC to increase the success rate. There were significant age differences (P = 0.041) in the medicated group and significant median PS differences (P = 0.010) in the naïve group between the successful and unsuccessful outcomes of TWOC. The multivariate logistic regression model demonstrated that age <80 years in medicated patients (P = 0.042, odds ratio [OR] 1.701) and PS <2 in naïve patients (P = 0.001, OR 2.710) were significant independent predictors of successful TWOC outcomes. This is the first study classifying patients with urinary retention according to medication status. Both medicated and naïve groups had different patient backgrounds and TWOC outcome predictors, suggesting a discrepant etiology behind urinary retention. Hence, acute urinary retention management in men should vary based on medication status for male lower urinary tract symptoms when urinary retention is diagnosed.

Real-world analysis of first-line afatinib in patients with EGFR-mutant non-small cell lung cancer and brain metastasis: survival and prognostic factors.

Overall survival (OS) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs) is poor. We aimed to identify prognostic factors and ascertain treatment outcomes of first-line afatinib for patients with epidermal growth factor receptor (EGFR)-mutant NSCLC with BM in a real-world setting. This retrospective observational study reviewed electronic records of patients with EGFR-mutant NSCLC who received first-line afatinib treatment between October 2014 and October 2019 in 16 hospitals across South Korea. The Kaplan-Meier method estimated time on treatment (TOT) and OS; multivariate analyses were performed using Cox proportional hazards (PH) models. Among 703 patients who received first-line afatinib, 262 (37.3%) had baseline BM. Of 441 patients without baseline BM, 92 (20.9%) developed central nervous system (CNS) failure. Compared with patients without CNS failure, those with CNS failure during afatinib treatment were younger (P=0.012), had a higher Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P<0.001), increased metastatic site involvement (P<0.001), advanced stage disease (P<0.001), with liver metastasis (P=0.008) and/or bone metastasis (P<0.001) at baseline. Cumulative incidence of CNS failure in years 1, 2 and 3 was 10.1%, 21.5% and 30.0%, respectively. In multivariate analysis, cumulative incidence was significantly higher in patients with ECOG PS ≥2 (P<0.001), uncommon EGFR mutations (P=0.001), and no baseline pleural metastasis (P=0.017). Median TOT was 16.0 months (95% CI: 14.8-17.2) and, in patients with CNS failure, without CNS failure, and with baseline BM was 12.2, 18.9, and 14.1 months, respectively (P<0.001). Median OS was 52.9 months (95% CI: 45.4-60.3) and, in patients with CNS failure, without CNS failure, and with baseline BM was 29.1, 67.3 and 48.5 months, respectively (P<0.001). First-line afatinib in the real-world setting showed clinically meaningful effectiveness in patients with EGFR-mutant NSCLC and BM. CNS failure was a poor prognostic factor for TOT and OS correlating with younger age, poor ECOG PS, higher metastatic number, advanced disease stage, uncommon EGFR mutations, and baseline liver and/or bone metastases.

Patient-reported ability to walk 4m and to wash: New clinical endpoints and predictors of survival in patients with pre-terminal cancer.

Maintaining the ability to perform self-care is a critical goal in patients with cancer. We assessed whether the patient-reported ability to walk 4m and wash oneself predict survival in patients with pre-terminal cancer. We performed a prospective observational study on 169 consecutive hospitalized patients with cancer (52% female, 64±12years) and an estimated 1-12months prognosis at an academic, inpatient palliative care unit. Patients answered functional questions for 'today', 'last week', and 'last month', performed patient-reported outcomes (PROs), and physical function assessments. Ninety-two (54%) patients reported the ability to independently walk 4m and 100 (59%) to wash 'today'. The median number of days patients reported the ability to walk 4m and wash were 6 (IQR 0-7) and 7 (0-7) days ('last week'); and 27 (5-30) and 26 (10-30) days ('last month'). In the last week, 32% of patients were unable to walk 4m on every day and 10% could walk on 1-3days; 30% were unable to wash on every day and 10% could wash on 1-3days. In the last months, 14% of patients were unable to walk 4m on every day and 10% could only walk on 1-10days; 12% were unable to wash on every day and 11% could wash on 1-10days. In patients who could walk 'today' average 4m gait speed was 0.78±0.28m/s. Patients who reported impaired walking and washing experienced more symptoms (dyspnoea, exertion, and oedema) and decreased physical function (higher Eastern Cooperative Oncology Group Performance Status, and lower Karnofsky Performance Status and hand-grip strength [unable vs. able to walk 'today': 205±87 vs. 252±78 Newton, P=0.001; unable vs. able to wash 'today': 204±86 vs. 250±80 Newton, P=0.001]). During the 27months of observation, 152 (90%) patients died (median survival 46days). In multivariable Cox proportional hazards regression analyses, all tested parameters were independent predictors of survival: walking 4m 'today' (HR 0.63, P=0.015), 'last week' (per 1day: HR 0.93, P=0.011), 'last month' (per 1day: HR 0.98, P=0.012), 4m gait speed (per 1m/s: HR 0.45, P=0.002), and washing 'today' (HR 0.67, P=0.024), 'last week (per 1 day HR 0.94, p=0.019), and 'last month' (per 1day HR 0.99, P=0.040). Patients unable to walk and wash experienced the shortest survival and most reduced functional status. In patients with pre-terminal cancer, the self-reported ability to walk 4m and wash were independent predictors of survival and associated with decreased functional status.

Machine learning-based algorithms to predict severe psychological distress among cancer patients with spinal metastatic disease

BACKGROUND CONTEXTMetastatic spinal disease is an advanced stage of cancer patients and often suffer from terrible psychological health status; however, the ability to estimate the risk probability of this adverse outcome using current available data is very limited. PURPOSEThe goal of this study was to propose a precise model based on machine learning techniques to predict psychological status among cancer patients with spinal metastatic disease. STUDY DESIGN/SETTINGA prospective cohort study. PATIENT SAMPLEA total of 1043 cancer patients with spinal metastatic disease were included. OUTCOME MEASURESThe main outcome was severe psychological distress. METHODSThe total of patients was randomly divided into a training dataset and a testing dataset on a ratio of 9:1. Patients' demographics, lifestyle choices, cancer-related features, clinical manifestations, and treatments were collected as potential model predictors in the study. Five machine learning algorithms, including XGBoosting machine, random forest, gradient boosting machine, support vector machine, and ensemble prediction model, as well as a logistic regression model were employed to train and optimize models in the training set, and their predictive performance was assessed in the testing set. RESULTSUp to 21.48% of all patients who were recruited had severe psychological distress. Elderly patients (p<0.001), female (p =0.045), current smoking (p=0.002) or drinking (p=0.003), a lower level of education (p<0.001), a stronger spiritual desire (p<0.001), visceral metastasis (p=0.005), and a higher Eastern Cooperative Oncology Group (ECOG) score (p<0.001) were significantly associated with worse psychological health. With an area under the curve (AUC) of 0.865 (95% CI: 0.788–0.941) and an accuracy of up to 0.843, the gradient boosting machine algorithm performed best in the prediction of the outcome, followed by the XGBooting machine algorithm (AUC: 0.851, 95% CI: 0.768–0.934; Accuracy: 0.826) and ensemble prediction (AUC: 0.851, 95% CI: 0.770–0.932; Accuracy: 0.809) in the testing set. In contrast, the AUC of the logistic regression model was only 0.836 (95% CI: 0.756–0.916; Accuracy: 0.783). CONCLUSIONSMachine learning models have greater predictive power and can offer useful tools to identify individuals with spinal metastatic disease who are experiencing severe psychological distress.

Characterization and prognostic factors of secondary to MDS/MPN and therapy-related AML: a single-center study

Introduction: Secondary acute myeloid leukemia (sAML) accounts for 15–30% of overall AML cases and is associated with shorter survival compared to de novo AML. The pathogenetic spectrum of sAML is heterogeneous, i.e. therapy-related AML (tAML) arises from prior cytotoxic, radiation, or immunosuppressive therapy, while myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)-AML develops from a previous clonal disorder of hematopoiesis. Material and methods: We performed a single-center retrospective analysis of MDS/MPN-AML and tAML patients diagnosed between 2013 and 2018 in the Hematology Department of the Medical University in Lodz, Poland. Simultaneously, demographic data, clinical factors, and laboratory findings were collected. For statistical analysis, we used Cox proportional hazard models and log-rank tests. Results: The study included 110 patients with either MDS/MPN-AML (n = 78) or tAML (n = 32), with a median age of 66 years (range 31–86). The median follow-up was 3.2 months [95% confidence interval (CI): 2.5–5.3]. The median overall survival (OS) for MDS/MPN-AML patients was 4.1 months (95% CI: 2.5–7.0) and for tAML it was 2.8 months (95% CI: 1.6-5.6). In multivariate Cox regression model for OS, factors such as age at diagnosis [hazard ratio (HR) 1.03, 95% CI: 1.00–1.06], higher Eastern Cooperative Oncology Group score (HR 1.85, 95% CI: 1.08–3.15), hypoalbuminemia (HR 3.20, 95% CI: 1.95–5.24) and percentage of bone marrow blasts infiltration (HR 1.01, 95% CI: 1.00–1.03) were independent predictors of poor survival for the whole cohort. On the other hand, the intensive treatment approach was related to longer survival (HR 0.42, 95% CI: 0.21–0.82). There were no differences in OS between MDS/MPN-AML and tAML ( p = 0.81). Conclusion: The poor treatment outcomes for sAML consist of a combination of low response rate and high early mortality. The positive influence of intensive chemotherapy should be highlighted, but nevertheless, optimizing treatment for thishigh-risk subpopulation remains crucial.

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis.

To identify the potential key genes of ferroptosis in the pathogenesis of lung cancer with bone metastasis (LCBM) by bioinformatics analysis to provide new targets for treating LCBM and an indicator for early monitoring. We first obtained differentially expressed genes (DEGs) associated with ferroptosis from the Gene Expression Omnibus (GEO) database. MiRWalk 2.0 was used to predict the key microRNAs (miRNAs) and construct related gene-miRNA interaction networks. The functional enrichment analysis of key miRNAs was performed using the miEAA database. Finally, the clinical data of 105 lung cancer patients were retrospectively analyzed, and logistic regression analysis was conducted to assess the relationship between serum alkaline phosphatase (ALP), neuron-specific enolase (NSE), and bone metastasis in lung cancer patients, and a receiver operating characteristic (ROC) curve was drawn. We identified 15 ferroptosis-related genes that were differentially expressed in lung cancer bone metastasis. GO and KEGG enrichment analyses suggested that these genes may affect the oxidative stress response, hypoxia response, rough endoplasmic reticulum, mitochondrial outer membrane, iron-sulfur cluster binding, virus receptor activity, central carbon metabolism in cancer, the interleukin-17 (IL-17) signaling pathway, and other aspects to participate in the occurrence and development of lung cancer bone metastasis. Among the 105 lung cancer patients included in the study, 39 cases had bone metastasis, and the incidence rate was 37.14%. A high Eastern Cooperative Oncology Group (ECOG) score and serum ALP and NSE overexpression were associated with bone metastasis in patients with lung cancer. By assessing the risk of bone metastasis in patients with lung cancer, we found that the Area Under Curves (AUCs) of serum ALP and NSE alone and combined were >0.70. The differentially expressed ferroptosis-related genes and predicted miRNA regulatory network in lung cancer bone metastasis and the related functional enrichment analysis provide new targets for the treatment of lung cancer bone metastasis. At the same time, from a serological perspective, it was found that early monitoring of serum ALP and NSE expression in patients with lung cancer could be considered to assess the risk of bone metastasis in the future.

Metabolic Tumor Volume Measured by 18F-FDG PET/CT is Associated with the Survival of Unresectable Hepatocellular Carcinoma Treated with PD-1/PD-L1 Inhibitors Plus Molecular Targeted Agents.

The combination of PD-1/PD-L1 inhibitors and molecular targeted agents showed promising efficacy for unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the prognostic value of metabolic parameters from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in patients with uHCC underwent the combined therapies. Patients with uHCC treated with a combination of immunotherapy and targeted therapy who underwent baseline 18F-FDG PET/CT between July 2018 and December 2021 were recruited retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake values (SUVmax), and clinical and biological parameters were recorded. A multivariate prediction model was developed for overall survival (OS) using these parameters together with clinical prognostic factors. Seventy-seven patients were finally included. The median OS was 16.8 months. We found that a high MTV (≥39.65 cm3 as the median value) was significantly associated with OS (P<0.05). In multivariate analyses for OS, a high MTV, high Eastern Cooperative Oncology Group performance status (ECOG-PS, ≥1), Child-Pugh (B-C) grade, and the presence of bone metastasis were significantly associated with poor OS (HR 1.371, HR 3.73, HR 15.384, and HR 2.994, all P<0.05, respectively). A multivariate prognostic model including MTV and prognostic factors, such as ECOG-PS, Child-Pugh grade, and bone metastasis, further improved the identification of different OS subgroups. High MTV is an adverse prognostic factor in patients with uHCC treated with a combination of immunotherapy and molecular targeted agents. Integrating PET/CT parameters with clinical prognostic factors could help to personalize immunotherapy.

Allogeneic hematopoietic stem cell transplantation for acquired severe aplastic anemia: a summary of a 20-year experience.

Severe aplastic anemia (SAA) is a rare but potentially fatal disorder characterized by hypocellular bone marrow and resulting in pancytopenia. It can be cured with allogeneic hematopoietic stem cell transplantation (allo‑HSCT), especially in young individuals. The main objective of the study was to assess the safety of the procedure and to identify the factors influencing long‑term post‑transplant outcome. Using our institutional database, we performed a retrospective analysis of the patients with SAA allotransplanted in the years 2001-2021. Seventy patients (49 men) at a median age of 25 years at transplantation underwent allo‑HSCT. Thirty-eight patients received immunosuppressive treatment (IST) before transplantation. Twenty-one patients received grafts from human leukocyte antigen-matched sibling, 44 from unrelated donors, and 5 from haploidentical related donors. Peripheral blood remained the source of stem cells in the majority of patients. Primary graft failure was observed in 2 cases. The incidence of acute graft‑versus‑host disease (GVHD) was 44%, whereas chronic GVHD was observed only in 4 patients. Median follow‑up was 3 years (interquartile range, 0.45-11.5). Post‑transplant outcome was comparable between patients with upfront allo‑HSCT and those who relapsed after IST. In the univariable analysis, only a higher Eastern Cooperative Oncology Group (ECOG) score at transplantation and infections in the post‑transplant period were found to be associated with unfavorable outcome. Fifty‑three patients were alive at last contact. Most transplanted patients died due to infectious complications. A 2‑year overall survival was 73%. The results of allo‑HSCT in SAA are satisfactory and offer long‑term survival and good quality of life. Higher ECOG score and the presence of infections are associated with poor post‑transplant outcome.

Identification of FAT4 as a positive prognostic biomarker in DLBCL by comprehensive genomic analysis.

The molecular landscapes of diffuse large B-cell lymphoma (DLBCL) remained to be comprehensively investigated with an urgent need to identify novel prognostic biomarkers guiding prognostic stratification and disease monitoring. Baseline tumor samples of 148 DLBCL patients were analyzed using targeted next-generation sequencing (NGS) for mutational profiling, whose clinical reports were retrospectively reviewed. In this cohort, the subgroup of old DLBCL patients (age at diagnosis > 60, N = 80) exhibited significantly higher Eastern Cooperative Oncology Group scores and International Prognostic Index than their young counterparts (age at diagnosis ≤ 60, N = 68). As revealed by the NGS results, PIM1 (43.9%), KMT2D (31.8%), MYD88 (29.7%), and CD79B (27.0%) were identified as the most frequently mutated genes. Aberrations of genes of the immune escape pathway were significantly enriched in the young subgroup, while the altered epigenetic regulators were more abundant in the old patients. FAT4 mutation was identified as a positive prognostic biomarker, associated with longer progression-free survival and overall survival in the entire cohort and the old subgroup, using the Cox regression analyses. However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research.

Factors Impacting Quality of Life of Caregivers of Cancer Patients in the Sub-Himalayan Region: A Cross-Sectional Study.

Background Caregivers of cancer patients experience excessive emotional and financial stress. Objective To determine the quality of life (QOL) of caregivers of cancer patients and factors affecting it in caregivers attending the OPD of a governmental tertiary care cancer center in the sub-Himalayan region. Methods A cross-sectional observational study was used. A pre-validated caregiver quality of life (CQOL) questionnaire was completed by consenting caregivers of 96 outpatient attendees. Results The mean total QOL scores were higher in attendants of subjects who did not undergo surgery versus those who underwent surgery (p-value: 0.04) and in those who received 0-5 versus >5 chemotherapy cycles (p-value: 0.015). On subdomain analyses, the burden was significantly greater in caregivers of patients who did not undergo surgery (p-value: 0.02) and had a higher Eastern Cooperative Oncology Group (ECOG) scale (p-value: 0.03). Disruptiveness was significantly higher in married individuals (p-value: 0.01) and those aged between 36 and 60 years (p-value: 0.003). Positive adaptation was worse in caregivers with another family member suffering from chronic illness (p-value: 0.041) and in professional and skilled workers (p-value: 0.03). The greater financial burden was experienced by caregivers belonging to lower socioeconomic status (p-value: 0.03). On putting these factors in the regression model, the non-specific domain of 0-5 cycles had poor CQOL, i.e., higher scores. The burden score was more in ECOG stages 3 and 4 in comparison with stages 1 and 2. Married individuals had significant disruption. Individuals aged between 36 and 60 years perceived more disruption in their lives. A more financial impact was observed on the lower middle and lower class compared to the upper and upper middle class. Conclusion Caregivers of cancer patients experience significant stress and burden. Counseling and social and financial support to caregivers may help improve CQOL.

Effectiveness and safety of anti-PD-1 monotherapy or combination therapy in Chinese advanced gastric cancer: A real-world study.

Gastric cancer (GC) is one of the most frequently diagnosed cancers and one of the leading causes of cancer deaths worldwide, especially in eastern Asia and China. Anti-PD-1 immune checkpoint inhibitors, Pembrolizumab and Nivolumab, have been approved for the treatment of locally advanced or metastatic gastric or gastroesophageal junction cancer (GC/GEJC). Our study evaluated the effectiveness and safety of anti-PD-1-based treatment (monotherapy or combination therapy) in Chinese patients with advanced or metastatic GC/GEJCs in a real-world setting. A retrospective cohort study was conducted, and 54 patients from May 31, 2015, to May 31, 2021, were included in our analysis, including 19 patients treated with anti-PD-1 monotherapy and 35 patients treated with anti-PD-1 combination therapy. Demographic and clinical information were evaluated. Clinical response, survival outcomes, and safety profile were measured and analyzed. Overall, the median overall survival (mOS) was 11.10 months (95% CI, 7.05-15.15), and the median progression-free survival (mPFS) was 3.93 months (95% CI, 2.47-5.39). Of the patients, 16.7% achieved a clinical response, and 72.2% achieved disease control. Prolonged overall survival (OS) and progression-free survival (PFS) and increased clinical response were observed in the combination group compared with the monotherapy group, although statistical significance was not reached. In subgroups with live metastases or elevated baseline neutrophil-to-lymphocyte ratio (NLR) levels, combination therapy outperformed anti-PD-1 alone in survival outcomes. Patients treated with anti-PD-1 monotherapy (n = 5, 26.3%) had fewer treatment-related adverse events (TRAEs) than those in the combination group (n = 22, 62.9%). There were also fewer patients with TRAEs of grades 3-5 with monotherapy (n = 2, 10.5%) than with combination therapy (n = 7, 20.0%). Pneumonitis in three patients was the only potential immune-related adverse event reported. Anti-PD-1-based monotherapy and combination therapy showed favorable survival outcomes and manageable safety profiles in advanced or metastatic GC/GEJCs. In clinical treatment, immunotherapy should be an indispensable choice in the treatment strategy for GC/GEJC. Patients with a heavy tumor burden and more metastatic sites might benefit more from combination therapy. Elderly patients and patients with more treatment lines or high Eastern Cooperative Oncology Group (ECOG) performance scores might be more suitable for immune monotherapy, and some clinical benefits have been observed.

Symptomatic bone marrow metastases in breast cancer: A retrospective cohort study.

Breast cancer symptomatic bone marrow metastasis (BMM) is rare and has a poor prognosis. Chemotherapy is usually the primary treatment, but it has limited efficacy, resulting in dose reduction and a decrease in quality of life due to the adverse effects of the agent. Other than chemotherapy, there are no other treatment studies for BMM. This study aimed to explore the clinicopathological characteristics of BMM patients with breast cancer, the prognosis using different treatment modalities, and the risk factors that affect the prognosis. This retrospective study included patients diagnosed with breast cancer BMM from January 2018 to January 2022 in the Cancer Center of the First Hospital of Jilin University. The analysis focused on the characteristics of the patients, the treatment regimen, and the prognosis. Of 733 patients with advanced breast cancer, 33 patients were identified with BMM. All patients showed a hemoglobin decrease, and 25 (75.75%) presented with a fever of unknown origin. As for the metastasis breast cancer subtype, 25 (75.75%) were hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative, three (9.09%) had HER2 overexpression, and five (15.15%) were triple negative. The BMM patients had a median progression-free survival (PFS) of 7 months (1-21 months) and a median overall survival (OS) of 18 months (2-108 months). Among 25 HR+/HER2- BMM patients treated with different modalities, the median OS of the endocrine therapy (ET) group was 23 months, compared with 5 months in the chemotherapy group. Cox proportional hazards models suggested that higher Eastern Cooperative Oncology Group (ECOG) scores and old age were associated with shorter survival. When breast cancer patients present with anemia and fever of unknown origin, BMM should be considered. For HR+/HER2- patients with good physical status and can receive active treatment, CDK4/6 inhibitors combined with ET can be used to control disease progression, improve quality of life, and prolong survival.

Risk Factors for Carbapenem Resistant Gram Negative Bacteria (CR-GNB) Carriage Upon Admission to the Gastroenterology Department in a Tertiary First Class Hospital of China: Development and Assessment of a New Predictive Nomogram.

With the increasing number of critically ill patients in the gastroenterology department (GED), infections associated with Carbapenem resistant gram-negative bacteria (CR-GNB) are of great concern in GED. As the turn-around time (TAT) for a positive screening culture result is slow, contact precaution and pre-emptive isolation, cohorting methods should be undertaken immediately on admission for high-risk patients. Accurate prediction tools for CR-GNB colonization in GED can help determine target populations upon admission. And thus, clinicians and nurses can implement preventive measures more timely and effectively. The purpose of the current study was to develop and internally validate a CR-GNB carrier risk predictive nomogram for a Chinese population in GED. Based on a training dataset of 400 GED patients collected between January 2020 and December 2021, we developed a model to predict CR-GNB carrier risk. A rectal swab was used to evaluate the patients' CR-GNB colonization status microbiologically. We optimized features selection using the least absolute shrinkage and selection operator regression model (LASSO). In order to develop a predicting model, multivariable logistic regression analysis was then undertaken. Various aspects of the predicting model were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping. The prediction nomogram includes the following predictors: Transfer from another hospital (Odds ratio [OR] 3.48), High Eastern Cooperative Oncology Group (ECOG) performance status (OR 2.61), Longterm in healthcare facility (OR 10.94), ICU admission history (OR 9.03), Blood stream infection history (OR 3.31), Liver cirrhosis (OR 4.05) and Carbapenem usage history within 3 month (OR 2.71). The model demonstrated good discrimination and good calibration. With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can take more timely infection preventive measures on isolation, cohorting and medical interventions.