Performance Status Research Articles

QLTI-08. PREDICTING POOR HIGH-VALUE CARE OUTCOMES FOLLOWING SURGICAL RESECTION OF MULTIFOCAL GLIOBLASTOMA

Abstract Presenting with dismal prognoses, treatment of multifocal GBM (mGBM) requires extensive medical infrastructure. Individualized assessment for patients at risk of extended length of stay (LOS) and nonroutine discharge disposition, described as high-value healthcare outcomes, has not previously been described. To develop predictive models for extended LOS and nonroutine discharge disposition for mGBM patients. All mGBM patients undergoing surgical resection at our institution (January 1, 2009-December 31, 2020) were included. Predictive models for nonroutine discharge disposition (discharge to a non-home environment) and extended LOS [upper quartile of the LOS for all patients included in the present study’s cohorts (>6 days)] were developed using multivariate logistic regression models. Optimism-corrected C-statistics for each model were calculated using 1000 bootstrapped samples in order to correct for potential bias associated with the limited population size. The Hosmer-Lemeshow test was used to evaluate model goodness of fit and calibration. A total of 137 mGBM patients were included in the present study. Most patients were male (40.1%), white (83.2%), not Hispanic/Latino (97.8%), not married (55.5%) and underwent elective surgery (85.4%). The average age among our patient cohort was 55.41 ± 13.17, the average KPS score was 77.23 ± 14.54 and the average mFI-5 was 0.613 ± 0.760. On bivariate analysis, older age (p=0.015) and decreasing Karnofsky Performance Status (KPS) score (p<0.001) were significantly associated with nonroutine discharge disposition while emergency admission (p=0.010) and increasing frailty (mFI-5) score (p=0.003) were significantly associated with extended LOS. On multivariate analysis, increasing age (p=0.031) and decreasing KPS (p<0.001) predicted nonroutine discharge while emergent admission (p=0.023) and greater mFI-5 (p=0.044) predicted extended LOS. Our models for nonroutine discharge and extended LOS had optimism-correct c-statistics of 0.7507 and 0.7309 respectively and displayed adequate calibration. Following external validation, our models may have utility as a risk stratification tool for this multifocal GBM patient populations.

Postoperative Karnofsky performance status prediction in patients with IDH wild-type glioblastoma: A multimodal approach integrating clinical and deep imaging features

Background and purpose Glioblastoma is a highly aggressive brain tumor with limited survival that poses challenges in predicting patient outcomes. The Karnofsky Performance Status (KPS) score is a valuable tool for assessing patient functionality and contributes to the stratification of patients with poor prognoses. This study aimed to develop a 6-month postoperative KPS prediction model by combining clinical data with deep learning-based image features from pre- and postoperative MRI scans, offering enhanced personalized care for glioblastoma patients. Materials and methods Using 1,476 MRI datasets from the Brain Tumor Segmentation Challenge 2020 public database, we pretrained two variational autoencoders (VAEs). Imaging features from the latent spaces of the VAEs were used for KPS prediction. Neural network-based KPS prediction models were developed to predict scores below 70 at 6 months postoperatively. In this retrospective single-center analysis, we incorporated clinical parameters and pre- and postoperative MRI images from 150 newly diagnosed IDH wild-type glioblastoma, divided into training (100 patients) and test (50 patients) sets. In training set, the performance of these models was evaluated using the area under the curve (AUC), calculated through fivefold cross-validation repeated 10 times. The final evaluation of the developed models assessed in the test set. Results Among the 150 patients, 61 had 6-month postoperative KPS scores below 70 and 89 scored 70 or higher. We developed three models: a clinical-based model, an MRI-based model, and a multimodal model that incorporated both clinical parameters and MRI features. In the training set, the mean AUC was 0.785±0.051 for the multimodal model, which was significantly higher than the AUCs of the clinical-based model (0.716±0.059, P = 0.038) using only clinical parameters and the MRI-based model (0.651±0.028, P<0.001) using only MRI features. In the test set, the multimodal model achieved an AUC of 0.810, outperforming the clinical-based (0.670) and MRI-based (0.650) models. Conclusion The integration of MRI features extracted from VAEs with clinical parameters in the multimodal model substantially enhanced KPS prediction performance. This approach has the potential to improve prognostic prediction, paving the way for more personalized and effective treatments for patients with glioblastoma.

CTIM-19. A PHASE 1, SAFETY LEAD-IN AND RANDOMIZED, OPEN-LABEL, PERIOPERATIVE STUDY OF VORASIDENIB COMBINED WITH PEMBROLIZUMAB IN RECURRENT OR PROGRESSIVE ENHANCING IDH-1 MUTANT GLIOMA: TRIAL IN PROGRESS

Abstract BACKGROUND Vorasidenib (VOR) is an oral, brain-penetrant dual inhibitor of isocitrate dehydrogenase 1/2 mutant (mIDH1/2) enzymes. VOR is being investigated in a phase 3 study in residual or recurrent grade 2 non-enhancing gliomas, in which interim analysis showed VOR significantly improved progression-free survival and delayed time to next intervention. A prior neoadjuvant perioperative study in recurrent, non-enhancing grade 2/3 gliomas showed that VOR treatment was associated with interferon signal activation and increased T-cell infiltration, suggesting 2-hydroxyglutarate suppression may prime the tumor immune microenvironment for immune checkpoint blockade. This study (NCT05484622) evaluates the safety and tolerability of VOR+pembrolizumab to determine the recommended combination dose (RCD) of VOR (safety lead-in phase) and evaluates CD3+ T-cell infiltration in tumors following a 28-day preoperative period. METHODS Enrollment: US patients with recurrent or progressive grade 2/3 mIDH1 R132H glioma. Key eligibility: measurable enhancing disease, Karnofsky Performance Status ≥70, resectable (perioperative phase only). Following a March 2024 protocol amendment, inclusion criteria were expanded to include patients with oligodendroglioma in addition to patients with astrocytoma. Safety lead-in dosing: Cohort 1, VOR 40mg QD+pembrolizumab 200mg Q3W in 21-day cycles. The perioperative phase is randomized 1:1:1 to preoperative combination, VOR 40mg QD, or untreated for 28 (+7) days; all patients could opt to receive the VOR RCD in combination with pembrolizumab 200mg Q3W postoperatively. Primary objectives: safety and tolerability of VOR RCD administered with pembrolizumab; CD3+ T-cell infiltration in resected tumors following presurgical treatment with combination compared to untreated tumors. RESULTS Seven patients with recurrent or progressive enhancing grade 2/3 astrocytoma with an mIDH1 R132H were dosed in the safety lead-in phase. No dose-limiting toxicities were detected during this phase. CONCLUSION VOR 40mg QD+pembrolizumab 200mg Q3W was confirmed as the RCD for the perioperative phase. This phase was opened to enrollment in May 2023, and recruitment is ongoing.

BIOS-03. CLINICAL PRESENTATION, MANAGEMENT, AND OUTCOME IN NEUROLYMPHOMATOSIS: A SYSTEMATIC REVIEW AND ANALYSIS OF INDIVIDUAL PATIENT DATA FROM 459 CASES

Abstract BACKGROUND Neurolymphomatosis (NL) refers to lymphomatous infiltration of the peripheral nervous system (PNS). NL diagnosis and treatment are challenging given the broad differential diagnosis of peripheral neuropathy, the lack of larger cohorts and the subsequent unavailability of prognostic factors or consensus therapy. This study aimed to define characteristics and prognostic factors of NL. METHODS A systematic review of the literature (2004-2023) was performed using PubMed and Scopus databases and reported following PRISMA guidelines. Clinical, radiological, pathological and outcome information were extracted. Multivariable survival analyses were performed using Cox proportional hazard models. RESULTS A total of 459 NL cases from 264 studies were accumulated. NL was the first manifestation of malignancy (primary NL) in 197 patients. PNS relapse of known non-Hodgkin lymphoma (secondary NL) occurred in 262 cases after a median 12 months. NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Infiltrated structures included peripheral nerves (56%), nerve roots (52%), plexus (33%) and cranial nerves (32%). Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (> 90%). Post mortem diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. Median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% confidence interval (CI): 0.25-0.78; p = 0.005), performance status (ECOG < 2, HR: 0.30; 95% CI: 0.18-0.52; p < 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI: 0.28-0.73; p = 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters. CONCLUSIONS Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Rituximab-based therapy improves NL outcome. Findings may assist clinicians in early recognition, prognostic stratification, and treatment of NL.

QLTI-03. REAL-WORLD PARADIGM FOR TREATMENT OF PRIMARY CNS LYMPHOMA PATIENTS IN CLINICAL PRACTICE

Abstract Although high-dose methotrexate (HD-MTX) is the foundation of induction therapy for primary CNS lymphoma (PCNSL), a gold-standard regimen has yet to be established. A 10-case-based survey, to assess the practice patterns at key decision-points in adult PCNSL management outside of clinical trials, was distributed through IPCG, HOVON, and AAN Neuro-Oncology Section. Eighty-five responses were collected from North American (N=42), European (N=33), Asian (N=7), and other countries (N=3) from neurologist neurooncologists (N=35), hem-onc neurooncologists (N=24), hematologist-oncologists (N=18), neurosurgeons (N=5), radiation-oncologist (N=2), and hematopathologist (N=1). The most common first-line induction regimen was R-MP+/-V: rituximab, HD-MTX, procarbazine, +/-vincristine (N=28) followed by MATRix: HD-MTX, cytarabine, thiotepa, rituximab (N=23), then R-MT: rituximab, HD-MTX, temozolomide (N=19). For elderly patients, R-MP+/-V remained most common (N=32). The majority preferred to omit intra-CSF chemotherapy (N=50). The most preferred consolidation after complete response was high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT, N=57), or high-dose cytarabine (N=17) in elderly patients. In cases of partial response, the most common approach was still HDC-ASCT (N=24). For stable disease, participants would move to various salvage chemotherapy (N=33), continue additional induction (N=39), or to move to radiotherapy (N=10). If early progression was noted, the most preferred approach was non-methotrexate chemotherapy (N=31). For recurrences after previous complete response and HDC-ASCT consolidation, the majority preferred to try chemotherapy before moving to radiotherapy in scenarios < 1 year (N=64) or > 1 year from consolidation (N=68), and even if the performance status was poor (N=57). Close to half (N=34) participants felt there is a role for stereotactic radiosurgery in various clinical settings. This survey noted clear consensus to use multi-drug MD-MTX based chemotherapy, and common induction regimens, however, highlighted a great variety of treatment preferences after first-line therapy even amongst disease experts through clinical consortiums, suggesting likely wider range of treatments and disease response in larger community settings.

CTNI-45. PHASE 2 STUDY OF SORAFENIB, VALPROIC ACID, AND SILDENAFIL IN THE TREATMENT OF RECURRENT HIGH-GRADE GLIOMA

Abstract PURPOSE Here we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma. PATIENTS AND METHODS Eligible patients were 18 years of age and older with an Eastern Cooperative Oncology Group performance status of 0-2 and pathologically confirmed high-grade glioma (WHO grade 3 or 4), with documented CT or MRI progression or recurrence and measurable or evaluable disease. The treatment schedule was a combination of sorafenib, valproic acid, and sildenafil, each agent administered orally, twice daily continuously. A cycle consisted of 4 weeks. RESULTS Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%). For all evaluable patients, the median progression-free survival was 3.65 months and overall survival (OS) 10.0 months. There was promising evidence showing clinical activity and benefit. In the 33 evaluable patients, low protein levels of the chaperone GRP78 (HSPA5) was significantly associated with a better OS (p < 0.0026). A correlation between the expression of PDGFRa and OS approached significance (p < 0.0728). Five patients presently have a mean OS of 73.6 months and remain alive. CONCLUSIONS This is the first therapeutic intervention glioblastoma trial to significantly associate GRP78 expression to OS. Our data suggest that the combination of sorafenib tosylate, valproic acid, and sildenafil requires additional clinical development in the recurrent glioma population.

Tocilizumab for Advanced Non‐Small‐Cell Lung Cancer With Concomitant Cachexia: An Observational Study

ABSTRACTBackgroundCancer cachexia significantly contributes to morbidity and mortality in patients with non‐small‐cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin‐6 (IL‐6) play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab in the management of NSCLC with coexisting IL‐6‐elevated cachexia.MethodsIn this retrospective study, data were collected from patients with NSCLC and concurrent IL‐6‐elevated cachexia who received either tocilizumab plus antitumour therapy or antitumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at Week 12. The secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C‐reactive protein (CRP) and mGPS. Qualitative improvements in patient self‐rated appetite and fatigue were reported as exploratory analysis.ResultsThe study included 49 patients diagnosed with NSCLC and IL‐6‐elevated cachexia, Eastern Cooperative Oncology Group performance status of 2–4. Of these, 26 received tocilizumab in combination with antitumour therapy, and 23 received antitumour therapy alone. The majority of these patients were male (87.8%). Baseline characteristics were almost identical between the two groups. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08–0.38; p < 0.001). The rate of patients surviving with mGPS improvement at Week 12 was significantly higher in the tocilizumab group than in the control group (risk difference 0.88, 95% confidence interval 0.75–1.00; p < 0.001). Over the 12‐week period, significant improvements were observed in body weight, albumin, CRP and mGPS in the tocilizumab group compared to the control group (body weight: 5.15 ± 0.53 kg vs. −5.69 ± 0.76 kg, p = 0.041; albumin: 5.89 ± 0.70 g/L vs. −2.97 ± 0.71 g/L, p < 0.001; CRP: −91.50 ± 7.15 mg/L vs. 9.47 ± 13.69 mg/L, p < 0.001; mGPS: −1.61 ± 0.15 vs. 0.03 ± 0.08, p < 0.001). The tocilizumab group also displayed significantly higher rates of improvement in appetite and fatigue (both p < 0.001). The incidence of Grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab‐related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection.ConclusionTocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, CRP, mGPS and symptom burden in patients with NSCLC and concurrent IL‐6‐elevated cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option.

Predicting reprisal of solid cancer treatment and 60-month survival after Medical Intensive Care. A single-centre cohort study.

Introduction. Our study aimed to identify relevant features associated with the reprisal of antineoplastic treatment in patients with solid cancers after unplanned admittance to the intensive care unit (ICU) and to assess 60th-month survival in patients with solid neoplasms admitted to the ICU. Methods. This single-centre retrospective study of critically ill patients with active cancers was performed over a 13-year period (2005-2018). Patients’ characteristics, overall survival and antineoplastic treatment reprisal were extracted from digital medical files and compared. Results. 134 patients were included in the study. Solid neoplasms were mostly localised to the head and neck (n=53) followed by lung cancers (n=29). Sepsis was the leading cause of ICU admission (62.1%) with 41/82 patients presenting with septic shock. Antineoplastic treatments were resumed in 40 patients. An age ≤60 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1 were found to be predictors for treatment reprisal, with odd ratios of, respectively, 2.83 (95%CI, 1.15-6.99) and 5.45 (95%CI, 2.01-14.82); area under the ROC curve of 72% (95%CI, 63-81%). Survival after the immediate discharge from the ICU was 101/134 (75%) and the 60-month survival rate was 29% and significantly higher in the treatment-reprisal group. Conclusions. Age and ECOG PS were found to be predictors for treatment reprisal in patients with solid neoplasms admitted to the ICU. The latter benefit from better long-term survival.

Predictors of tolerability for postoperative adjuvant S1 plus docetaxel chemotherapy for gastric cancer: a multicenter retrospective study

Abstract Background Adjuvant docetaxel plus S1 (DS) chemotherapy after gastrectomy with D2 lymph node dissection is the standard treatment for stage III gastric cancer in Japan; however, some patients are unable to receive adequate drug administration because of the deterioration of their conditions. This study aimed to investigate the correlation between tolerability for postoperative adjuvant DS chemotherapy and prognosis, and the factors affecting tolerability. Methods This retrospective study involved patients with stage III gastric cancer who underwent curative resection between 2018 and 2021 from a multicenter database. Patients with a cumulative dose of docetaxel and S1 greater than 120 and 8400 mg/m2, respectively, were considered tolerable. The prognostic impact and factors predicting tolerability were analyzed. Results Of the 103 patients, the tolerable group comprised of 63 (61%) patients and had a significantly better 3-year recurrence-free survival than the intolerable group (83% vs. 64%, P = 0.02). Among the preoperative factors, only performance status (PS, P = 0.04) was significantly correlated with tolerability in the univariate analysis. Among the postoperative factors, PS (P = 0.001) and perioperative weight loss rate (P = 0.02) were significantly correlated with tolerability in the univariate analysis. The multivariate analysis showed significant differences in the PS (odds ratio [OR]: 4.94, 95% confidence interval [CI] 1.79–14.98, P = 0.002) and weight loss rate (OR: 1.10, 95% CI 1.01–1.21, P = 0.03). Conclusions Tolerance to postoperative adjuvant DS chemotherapy has a significant prognostic impact. Postoperative PS and perioperative weight loss rates were independent predictors of tolerability.

Dietary supplementation with citrus peel extract in transition period improves rumen microbial composition and ameliorates energy metabolism and lactation performance of dairy cows

BackgroundDuring the transition period, excessive negative energy balance (NEB) lead to metabolic disorders and reduced milk yield. Rumen microbes are responsible for resolving plant material and producing volatile fatty acids (VFA), which are the primary energy source for cows. In this study, we aimed to investigate the effect of citrus peel extract (CPE) supplementation on rumen microbiota composition, energy metabolism and milk performance of peripartum dairy cows.MethodsDairy cows were fed either a basal diet (CON group) or the same basal diet supplemented with CPE via intragastric administration (4 g/d, CPE group) for 6 weeks (3 weeks before and 3 weeks after calving; n = 15 per group). Samples of serum, milk, rumen fluid, adipose tissue, and liver were collected to assess the effects of CPE on rumen microbiota composition, rumen fermentation parameters, milk performance, and energy metabolic status of dairy cows.ResultsCPE supplementation led to an increase in milk yield, milk protein and lactose contents, and serum glucose levels, while reduced serum concentrations of non-esterified fatty acid, β-hydroxybutyric acid, insulin, aspartate aminotransferase, alanine aminotransferase, and haptoglobin during the first month of lactation. CPE supplementation also increased the content of ruminal VFA. Compared to the CON group, the abundance of Prevotellaceae, Methanobacteriaceae, Bacteroidales_RF16_group, and Selenomonadaceae was found increased, while the abundance of Oscillospiraceae, F082, Ruminococcaceae, Christensenellaceae, Muribaculaceae UCG-011, Saccharimonadaceae, Hungateiclostridiaceae, and Spirochaetaceae in the CPE group was found decreased. In adipose tissue, CPE supplementation decreased lipolysis, and inflammatory response, while increased insulin sensitivity. In the liver, CPE supplementation decreased lipid accumulation, increased insulin sensitivity, and upregulated expression of genes involved in gluconeogenesis.ConclusionsOur findings suggest that CPE supplementation during the peripartum period altered rumen microbiota composition and increased ruminal VFA contents, which further improved NEB and lactation performance, alleviated lipolysis and inflammatory response in adipose tissue, reduced lipid accumulation and promoted gluconeogenesis in liver. Thus, CPE might contribute to improve energy metabolism and consequently lactation performance of dairy cows during the transition period.

Use of follow-up psycho-oncology consultations in urological cancer after transition from inpatient to outpatient care

Background: In urological oncology, the physical and psychological effects of cancer and its treatment post-discharge highlight the importance of follow-up psycho-oncology consultations. This study examines their utilisation and identifies predictors in urological cancer patients after inpatient care. Methods: A prospective, single-centre clinical observational study was conducted. Inpatients with urological cancer and ≥ 5 points on the Distress Thermometer and/or request for psycho-oncological support were recruited, offered an initial psycho-oncology consultation, and up to five online or on-site appointments within three months of discharge. The following variables were collected: socio-demographics, psycho-oncological baseline documentation (PO-BADO), psychosocial distress (Distress Thermometer with problem list), anxiety and depressive symptoms (GAD-2 & PHQ-2), and performance status (ECOG). Results: A total of 501 patients were screened, 139 were included, and 108 were analysed. 25 patients used psycho-oncological follow-up care (n = 16 online). The final hierarchical model predicting the use of follow-up psycho-oncological support included the two predictors: age (OR 0.93, 95% CI 0.90-0.96) and anxiety (OR 1.60, 95% CI 1.11-2.44). Discussion: Nearly one in four urological cancer patients use follow-up psycho-oncology consultations, mostly online. Predictors for this usage are younger age and higher levels of anxiety. To improve care: 1) online services reduce barriers; 2) older patients require support with these services; and 3) screening specifically for depression is crucial to ensure that follow-up appointments are scheduled as a mandatory part of hospitalisation.

Quick Sequential Organ Failure Assessment (qSOFA) and Performance Status Scoring Systems as Prognostic Predictors in Pneumococcal Community-Acquired Pneumonia

Quick Sequential Organ Failure Assessment (qSOFA) and Performance Status Scoring Systems as Prognostic Predictors in Pneumococcal Community-Acquired Pneumonia

Morbidität und Mortalität nach NSCLC-Operationen bei älteren Patienten: Individualisierte Risikobewertung notwendig

Background: Reports from case series suggest that operative outcomes are comparable amongst different age groups following surgery with curative intent for non-small cell lung cancer (NSCLC). The purpose of this study was to compare morbidity and mortality after NSCLC surgery in older patients (≥ 75 years) versus younger patients (< 75 years) and identify independent predictive risk factors. Methods: We identified 2015 patients with postoperative stages IA to IIIA according to AJCC/UICC 7th edition who had undergone NSCLC surgery with curative intent at a single specialized lung cancer center from January 2010 to December 2015. A matched-pair analysis was performed on 227 older patients and corresponding 227 younger patients. Short-term surgical outcomes were postoperative morbidity, length of hospital stay, 30-day and 90-day mortality. Long-term operative outcomes were disease-free and overall survival. Results: 454 patients were included in the matched-pair analysis. 36% of younger patients developed postoperative complications versus 42% in older patients (p = 0.163). Age was not significantly associated with the occurrence of postoperative complications. Median length of hospital stay was 14 days in older patients and 13 days in younger patients (p = 0.185). 90-day mortality was 2.2% in younger patients compared to 4% in older patients (p = 0.424). In patients aged 75 and older impaired performance status (ECOG ≥ 1) was associated with decreased overall survival (HR = 2.15, CI 1.34–3.46), as were preoperative serum C-reactive protein / albumin ratio ≥ 0.3 (HR = 1.95, CI 1.23–3.11) and elevated preoperative serum creatinine levels ≥ 1.1 mg/dl (HR = 1.84, CI 1.15–2.95). In the younger cohort male sex (HR = 2.26, CI 1.17–4.36), postoperative stage III disease (HR 4.61, CI 2.23–9.54) and preoperative anemia (hemoglobin < 12 g/dl) (HR 2.09, CI 1.10–3.96) were associated with decreased overall survival.

Acute kidney injury in hematological patients treated with CAR-T cells: risk factors, clinical presentation and impact on outcomes.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, yet it carries significant risks, including acute kidney injury (AKI). In this study, we investigated the risk factors and clinical impact of AKI in patients undergoing CAR-T cell therapy. This retrospective study involved hematologic patients treated with CAR-T therapy. Clinical and laboratory data were collected, and clinical outcomes were monitored during follow-up after CAR-T infusion. AKI was defined according to KDIGO criteria. The outcome measures included early mortality, overall survival (OS), and disease-free survival (DFS). Among the 48 patients analyzed, 14 (29%) developed AKI, with a mean onset of 6 days after CAR-T infusion. The risk of AKI was associated with baseline performance status (OR 8.65, IC95% 6.2-12, p = 0.032) and the development of severe cytokine release syndrome post-therapy (OR 16.4 95%CI 1.9-138.5, p = 0.01). Patients with AKI more frequently required intensive care. Furthermore, severe AKI was independently associated with worse clinical outcomes, including reduced OS and DFS (HR 18.2, 95%CI 2.6-27.3, p = 0.003). Additionally, patients who developed AKI post-CAR-T therapy were more likely to progress to chronic kidney disease during follow-up. In conclusion, frail patients undergoing CAR-T therapy are at an increased risk of developing AKI, which can significantly affect both short- and long-term outcomes. Preventive strategies and early recognition of AKI are essential in these patients.

The advance of research on rhythmic gymnastics

This study conducted a systematic review of the existing literature on rhythmic gymnastics. Through searching databases such as PubMed, Web of Science, and Scopus, 37 out of 2319 articles were selected, covering training and physical fitness, nutrition and metabolism, as well as sports injuries and rehabilitation. The findings revealed that: (1) Core physical training significantly enhanced athletes’ performance; (2) Inadequate nutritional intake was prevalent; (3) The incidence of sports injuries was high, particularly those resulting from overtraining. The conclusion emphasizes the need to enhance strength training, optimize nutritional management, and further investigate injury prevention and rehabilitation measures to enhance athletes’ performance and health status.

Global Leadership Initiative on Malnutrition criteria: Clinical benefits for patients with gastric cancer.

Malnutrition is a prevalent condition among patients with gastric cancer and is associated with poor survival outcomes. This study aimed to evaluate the clinical utility of the Global Leadership Initiative on Malnutrition (GLIM) criteria in predicting survival among patients with gastric cancer. The multicenter retrospective cohort study (INSCOC study) included 1406 patients enrolled between December 2012 and April 2020, with follow-up data collected until June 2023. Various indices for muscle evaluation, such as calf circumference (CC) and body weight-standardized hand grip strength (HGS/W), were used to diagnose malnutrition. Kaplan-Meier curves were used to analyze the relationship between nutrition status, as defined by GLIM criteria, and survival outcomes in these patients. The analysis revealed that using CC or HGS/W as positive indicators of malnutrition effectively identified patients with survival-related malnutrition. The incidence of malnutrition was 54.5%, with patients' median overall survival times of 1169 days for stage I and 575 days for stage II cancer (P < 0.001). Malnutrition was identified as an independent risk factor for survival. Additionally, a nomogram developed through Cox regression analysis demonstrated precise predictive capability, incorporating factors such as tumor node metastasis staging, Karnofsky Performance Status Scale, direct bilirubin levels, and nutrition intervention. The study concludes that the GLIM criteria are effective in diagnosing malnutrition and predicting survival in patients with gastric cancer. Nutrition interventions significantly enhance survival outcomes, underscoring the importance of standardized nutrition treatments in improving patient prognosis.

Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.

Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC). The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy. Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described. A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7months, 20.3months, and 14.2months; p< 0.001) and OS (60.8months, 44.4 months, and 27.6 months; p< 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups. In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.

Impact of gastrectomy on efficacy and safety of second‐line chemotherapy patients with advanced gastric cancer: Exploratory analysis of two randomized phase III trials

AbstractAimsSecond‐line chemotherapy (SLC) improves survival in advanced gastric cancer (AGC). Although many patients receiving SLC have undergone gastrectomy, the impact of gastrectomy on SLC remains unclear.Patients and MethodsThe objective was to evaluate the impact of gastrectomy on SLC for AGC. A total of 290 eligible patients registered in two randomized phase III trials evaluating SLC for patients with AGC was classified into the prior gastrectomy group (PGG; n = 187) or the no gastrectomy group (NGG; n = 103). We compared overall survival (OS), progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety between these two groups. Adjusted OS and adjusted PFS were estimated using inverse probability of treatment weighting (IPTW).ResultsThe PGG had better performance status (p = 0.001), more prior platinum agent (p &lt; 0.001), and more frequent peritoneal metastasis (p = 0.006) than the NGG. The PGG had significantly better OS (13.8 vs. 9.3 mo; hazard ratio [HR]: 0.59; p &lt; 0.001) and PFS (4.7 vs. 2.8 mo; HR: 0.58; p &lt; 0.001) than the NGG. The PGG had significantly better adjusted OS (13.8 vs. 10.0 mo; IPTW HR: 0.66; p = 0.01) and adjusted PFS (4.3 vs. 3.2 mo; IPTW HR: 0.71; p = 0.027) than the NGG. No significant differences were observed in ORR and DCR. The incidence of Grade 3 or worse adverse events did not differ between the two groups except for a high incidence of anemia and diarrhea in the NGG.ConclusionPatients with previous gastrectomy are expected to have better survival outcomes when receiving second‐line irinotecan (IRI)‐based chemotherapy for AGC.

Serum CYFRA 21-1 as a Prognostic Marker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors

Background: A prognostic marker in patients with non-small-cell lung cancer (NSCLC) treated with anti-PD-1/PD-L1 antibodies must be established. This study explored serum cytokeratin fraction 21–1 (CYFRA 21-1), which represents a squamous cell histology, as a prognostic factor in anti-PD-1/PD-L1 antibody treatment, stratifying by histology and treatment regimen. Methods: This study retrospectively evaluated patients with advanced NSCLC without driver mutations receiving anti-PD-1/PD-L1 antibodies between November 2015 and March 2023. Cutoff values for CYFRA 21-1 and carcinoembryonic antigen (CEA) were 3.5 and 5.0 ng/mL, respectively. The Kaplan–Meier method and a log-rank test were conducted. The Cox proportional hazards model was utilized for univariate and multivariate analyses. Results: This study included 258 patients. The squamous NSCLC group demonstrated a shorter overall survival (OS) than the non-squamous NSCLC group (median, 17.8 vs. 23.7 months, p = 0.141). Patients with high serum CYFRA 21-1 and CEA levels exhibited a significantly shorter OS than those with normal levels (median, 11.7 vs. 32.7 months, p &lt; 0.005; 15.8 vs. 29.7 months, p &lt; 0.005). The multivariate analysis identified a performance status (PS) of ≥2, a PD-L1 expression of ≥50%, and a serum CYFRA 21-1 of &gt;3.5 ng/mL as independent prognostic factors. Patients with high serum CYFRA 21-1 levels exhibited a significantly shorter OS even focusing on non-squamous NSCLC, anti-PD-1/PD-L1 antibody and chemotherapy combination therapy, or anti-CTLA-4 antibody combination therapy. Conclusion: Serum CYFRA 21-1 is a poor prognostic marker for patients with NSCLC receiving anti-PD-1/PD-L1 antibody treatment even when stratifying by histology or treatment regimen.

Assessment of Professional Practices in the Care Pathway of Patients with Upper Aerodigestive Tract Cancer in a University Hospital

Objectives: The main objective of this study was to evaluate the alignment between treatment decisions made during multidisciplinary team meetings (MTMs) and the treatments received by patients with upper aerodigestive tract cancers. The secondary objective was to identify factors influencing potential discrepancies. Methods: This retrospective, single-center study was conducted at a tertiary referral center and included 147 patients diagnosed with squamous cell carcinoma of the upper aerodigestive tract. Patients were divided into two groups based on the match between MTM-decided and actual treatments. Multivariate analysis was performed to assess factors independently associated with discrepancies. Results: Out of 147 patients, 28 (19%) received treatment that did not align with MTM decisions. Among these, eight died before treatment, one patient refused care, five received supportive care, five patients underwent surgery, three received radiotherapy alone, one patient underwent surgery and adjuvant radiochemotherapy, one patient underwent surgery and adjuvant radiotherapy alone, three patients received radiochemotherapy, and one patient received palliative chemotherapy. Independent significant factors associated with non-concordance included poor performance status (PS) and treatment not received at a tertiary reference center. Treatment shifts mainly involved downgrading from curative to palliative care. Conclusions: This study highlights the importance of patient health status in determining deviations from MTM decisions. Further efforts should focus on improving the integration of patient comorbidities and health status into MTM decision-making to optimize care delivery.