Poor Eastern Cooperative Oncology Group Research Articles

Paraneoplastic neurological syndrome and its impact on the treatment outcomes of small-cell lung cancer: A single-center retrospective analysis.

Paraneoplastic neurological syndrome (PNS) is associated with small-cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real-world data from patients with PNS complicated by SCLC. Patients diagnosed with Stage II-IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3-4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23). A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS.

Predictive markers of response to immune checkpoint inhibitor rechallenge in metastatic non-small cell lung cancer.

The present study aims to evaluate the efficacy of rechallenge with immune checkpoint inhibitors (ICIs) compared to chemotherapy and the predictive role of clinical parameters in non-small cell lung cancer (NSCLC) patients who were rechallenged. The study included 113 metastatic NSCLC patients who had initially responded to ICIs and platinum-based chemotherapy, either in combination in the first line or sequentially in the first and second line, but later experienced disease progression. Of those patients, 52 later received ICI rechallenge and 61 were exposed to chemotherapy. In the rechallenge cohort, the median age was 67 years, 38 patients were men (73.1%), 26 (50.0%) had squamous cell carcinoma. Patients who underwent ICI rechallenge had longer overall survival (OS) compared to those who received chemotherapy (12.9 months vs. 9.6 months, P = 0.008). Multivariate analysis for progression-free survival (PFS) and OS revealed that poor Eastern Cooperative Oncology Group Performance Status (ECOG PS; PFS: P = 0.013 and OS: P = 0.037), absence of objective response during initial ICI therapy (PFS: P = 0.014 and OS: P = 0.028), and baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 3.8 (PFS: P = 0.001 and OS: P = 0.003) were negative predictive factors of ICI rechallenge. The three parameters were included in a risk model named as the NEO score, which stratified patients who received ICI rechallenge into two predictive groups. Patients with ECOG PS 0-1, objective response during initial ICI treatment, and NLR < 3.8 (favorable group) had longer PFS (8.6 months vs. 3.0 months, P < 0.001) and OS (16.6 months vs. 5.5 months, P < 0.001) compared to those with absence of all three markers (poor group). There was no association between the NEO score and survival outcomes in patients who did not undergo rechallenge. ICI rechallenge showed a survival benefit, particularly in NSCLC patients with NLR < 3.8, good ECOG PS, and objective response.

Development and Validation of a Clinical Prediction Model for Paclitaxel Hypersensitivity Reaction on the Basis of Real-World Data: Pac-HSR Score.

Paclitaxel is effective chemotherapy against various cancers but can cause hypersensitivity reaction (HSR). This study aimed to identify predictors associated with paclitaxel HSR and develop a clinical prediction model to guide clinical decisions. Data were collected from the medical records database of Rajavithi Hospital. Patients with cancer treated with paclitaxel from 2015 to 2022 were included, and a multivariable logistic regression analysis identified predictors associated with paclitaxel HSR. The scoring system was transformed and calibrated on the basis of diagnostic parameters. Discrimination and calibration performances were assessed. Internal validation was conducted using bootstrap resampling with 1,000 replications. This study involved 3,708 patients with cancer, with an incidence of paclitaxel HSR of 10.11%. An 11-predictor-based Pac-HSR scoring system was developed, involving the following factors: younger age; poor Eastern Cooperative Oncology Group performance status; previous history of paclitaxel HSR; medication allergy history; chronic obstructive airway disease; lung and cervical cancers; high actual dose of paclitaxel; no diphenhydramine premedication; low hemoglobin level; high WBC count; and high absolute lymphocyte count. The C-statistics was 0.73 (95% CI, 0.70 to 0.76), indicating acceptable discrimination. The P value of the Hosmer-Lemeshow goodness-of-fit test was 0.751. The ratio of observed and expected values was 1.00, indicating good calibration. At a cutoff point of 8, specificity was 75.28% and sensitivity was 57.07%. Internal validation indicated good performance with minimal bias, and decision curve analysis demonstrated improved prediction with the use of this scoring system in clinical decision making. This study developed the 11-predictor-based Pac-HSR scoring system for predicting paclitaxel HSR in patients with cancer. High-risk patients identified by this score should be prioritized for close monitoring and early treatment prophylaxis.

Patient- and Areal-Level Risk Factors Associated With Lung Cancer Mortality in Victoria, Australia: A Bayesian Spatial Survival Analysis.

In Australia, lung cancer is the leading cause of cancer-related deaths. In Victoria, the mortality risk is assumed to vary across Local Government Areas (LGAs) due to variations in socioeconomic advantage, remoteness, and healthcare accessibility. Thus, we applied Bayesian spatial survival models to examine the geographic variation in lung cancer survival in Victoria. Data on lung cancer cases were extracted from the Victorian Lung Cancer Registry (VLCR). To account for spatial dependence and risk factors of survival in lung cancer patients, we employed a Bayesian spatial survival model. Conditional Autoregressive (CAR) prior was assigned to model the spatial dependence. Deviance Information Criterion (DIC), Watanabe Akaike Information Criterion (WAIC), and Log Pseudo Marginal Likelihood (LPML) were used for model comparison. In the final best-fitted model, the Adjusted Hazard Ratio (AHR) with the 95% Credible Interval (CrI) was reported. The outcome variable was the survival status of lung cancer patients, defined as whether they survived or died during the follow-up period (death was our interest). Our study revealed substantial variations in lung cancer mortality in Victoria. Poor Eastern Cooperative Oncology Group (ECOG) performance status, diagnosed at a regional hospital, Small Cell Lung Cancer (SCLC), advanced age, and advanced clinical stage were associated with a higher risk of mortality, whereas being female, presented at Multidisciplinary Team (MDT) meeting, and diagnosed at a metropolitan private hospital were significantly associated with a lower risk of mortality. Identifying geographical disparities in lung cancer survival may help shape healthcare policy to implement more targeted and effective lung cancer care services.

Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer Under-Represented by Clinical Trials.

Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there is a clear efficacy-effectiveness gap whereby patients in the 'real world' seem to have more modest clinical outcomes compared to those enrolled in landmark clinical trials. This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics. In this review, we summarize the data outlining the evidence of ICIs in patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), underlying autoimmune disease (AID), older age, active brain metastases (BMs), and molecular aberrations such as EGFR mutations, ALK fusions, BRAF mutations and ROS1 fusions.

Predicting septic shock in obstructive pyelonephritis associated with ureteral stones: A retrospective study.

To identify the best combination of potential predictors of septic shock in patients with obstructive acute pyelonephritis associated with ureteral stones (OAPN-US) according to Sepsis-3 criteria. Patients who underwent percutaneous nephrostomy (PCN) with OAPN-US were retrospectively evaluated. Recursive feature elimination (RFE) was applied to patients with and without septic shock to identify factors associated with the prediction of progression to septic shock. We compared combinations of the selected features based on area under the receiver operating curve (AUROC) to determine which combination was most effective. This study included 81 patients who were treated with PCN due to OAPN-US. A comparison was made between 37 patients with septic shock (SS) and 44 patients without septic shock (NSS). SS group had a higher age, poorer Eastern Cooperative Oncology Group status, and significantly higher levels of positivity in urine cultures and blood cultures. There were also differences in laboratory tests between the 2 groups. Procalcitonin (PCT), international normalized ratio (INR), and absolute lymphocyte count (ALC) were selected based on RFE. We compared the predictive power for SS when each marker was used alone, when 2 markers were combined, and when all 3 markers were combined. Among these combinations, using all 3 variables together yielded the highest AUROC of 0.942. Of the 3 variables, PCT had the highest Gini importance score, indicating that it was the most influential factor. Clinical characteristics were different between the SS and the NSS groups. In patients with OAPN-US, the combination of PCT, ALC, and INR was an excellent predictor of septic shock.

Real-world efficacy of low dose osimertinib as second-line treatment in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer.

Response rates of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) to lower doses of osimertinib [20 mg once daily (OD) and 40 mg OD] are similar to those of the recommended dose of 80 mg OD, but there is a lack of real-world evidence on the effect of the lower doses of osimertinib on survival outcomes. We conducted this study to assess the efficacy and safety of lower osimertinib doses for patients with EGFR-mutated advanced NSCLC whose disease had progressed on earlier generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world clinical practice. This multicenter, retrospective study included patients with EGFR-mutated advanced NSCLC treated with low doses of osimertinib after failing first- or second-generation EGFR TKIs due to acquired T790M mutation. Data on demographics, staging, treatment history, best overall response rate (ORR) based on RECIST 1.1, and adverse events (AEs) were collected from the patients' case notes. Descriptive data were described in percentages and medians. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Of the 22 patients studied [males =8 and females =14; Eastern Cooperative Oncology Group (ECOG) 1 or 2 =7 and ECOG 3 or 4 =15], 45.5% were on 40 mg OD, 31.8% were on 80 mg every other day (EOD), and 22.7% on 40 mg EOD. First-line EGFR TKIs used included afatinib, erlotinib, and gefitinib. The ORR with lower doses of second-line osimertinib was 77.3%. Overall, the median PFS was 10.0 months [95% confidence interval (CI): 8.6-11.4] and median OS was 13.0 months (95% CI: 9.4-16.6). In patients with ECOG 1 or 2, the median PFS was 18.0 months (95% CI: 5.8-30.2) and the median OS was not reached at the time of analysis. In patients with poor ECOG performance status of 3 and 4, good survival outcomes were also seen with a median PFS of 7.0 months (95% CI: 4.7-9.3) and median OS of 10.0 months (95% CI: 7.5-12.5). All AEs except one case of paronychia were Grade 1. There were no Grade 3 or 4 AEs. Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment with first- or second-generation EGFR TKIs due to T790M mutation.

Pancreatic Cancer: A Retrospective Study From the Najran Region of Saudi Arabia.

Despite advances in treatment, pancreatic cancer frequently has a low survival rate due to its advanced-stage diagnosis. Treatment focuses on prolonging survival and maintaining quality of life. This study investigates the characteristics associated with survival in advanced pancreatic cancer patients treated at a single academic cancer center in Najran, Saudi Arabia. A retrospective chart review study covering the period January 1, 2015, and December 31, 2023, involved 80 adult patients with pathologically confirmed pancreatic cancer (ductal adenocarcinoma) at King Khalid Hospital in Najran, Saudi Arabia. Clinicopathological characteristics, therapy, response, and survival outcomes were all gathered and analyzed. The chi-squared test, Kaplan-Meier, and Cox proportional hazards method with hazard ratios (HR) and 95% confidence intervals (CI) were used for statistical analysis. The mean age was 65.7±14.1 years and 54 (67.5%) cases were male. The main symptom was abdominal pain (n=54, 67.5%), while jaundice was presented in 17 (21.2%) of cases. The baseline serum carbohydrate antigen 19-9 (CA 19-9) level varied among cases, with 35 (43.8%) having normal levels. The majority of cases (n=59, 73.8%) had distant metastases at the initial presentation, while 12 cases (15%) had localized disease (resectable), and 22 (27.5%) were locally advanced at the first presentation. The most commonly reported pathologic grade was poorly differentiated ductal adenocarcinoma in 39 (48.8%). FOLFIRINOX was used as first-line chemotherapy in 54 (67.5%) cases, while gemcitabine alone was used in 15 (18.8%) cases. First-line chemotherapy resulted in progressive disease in 30 (37.5%), stable disease in 30 (37.5%), and partial response in 14 (17.5%). With a mean follow-up time of 14.8±8.6 months, 57 (71.2%) were dead, where the main cause of death was disease progression (n=51, 89.5%). The median overall survival was 13.5 months, with a 12-month survival rate of 56% and a 36-month survival rate of 17%. The median cancer-specific survival was 16 months (95% CI: 13-22 months). The 12-month median cancer-specific survival was 61% (95% CI: 51-73%), and the 36-month median cancer-specific survival was 19% (95% CI: 10-34%). In univariate analysis, initial metastasis presentation (HR: 35.46; 95% CI: 4.90-256.83, p<0.001), poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (3-4) (HR: 2.34; 95% CI:1.34-4.09, p=0.003), and presence of multiple metastases (HR: 1.33; 95% CI: 1.09-1.62, p=0.004) were associated with worsened survival. Patients who received the first chemotherapy were associated with better survival (HR: 0.53; 95% CI: 0.29-0.98, p=0.043). Furthermore, the response rate in patients who received FOLFIRINOX was better than that of those who received gemcitabine alone, which was statistically significant (p=0.002). Our study showed that initial metastatic presentation, poor ECOG-PS, and the occurrence of numerous metastases were all linked with poor survival of patients with pancreatic adenocarcinoma. Additionally, FOLFIRINOX as a first-line treatment showed better survival rates than gemcitabine alone. Raising awareness among healthcare providers on the alarming signs of pancreatic cancer and the introduction of personalized oncology might improve the outcome of this fatal malignancy.

Risk factors for early mortality from lung cancer: evolution over the last 20 years in the French nationwide KBP cohorts

The impact of the most recent advances, including targeted therapies and immune checkpoint inhibitors, on early (3-month) mortality in lung cancer is unknown. The aims of this study were to evaluate the real-world rate of and risk factors for early mortality, as well as trends in early mortality over the last 20 years. The KBP prospective observational multicenter studies have been conducted every 10 years since 2000. These studies collect data on all newly diagnosed patients with lung cancer (all stages and histologies) over 1 year in non-academic public hospital pulmonology or oncology units in France. In this study, we analyzed data on patient and tumor characteristics from participants in the KBP-2020 cohort and compared the characteristics of patients who died within 3 months of diagnosis with those of all other patients within the cohort. We also carried out a comparative analysis with the KBP-2000 and KBP-2010 cohorts. Overall, 8999 patients from 82 centers were included in the KBP-2020 cohort. Three-month survival data were available for 8827 patients, of whom 1792 (20.3%) had died. Risk factors for early mortality were: male sex, age >70 years, symptomatic disease at diagnosis, ever smoker, weight loss >10 kg, poor Eastern Cooperative Oncology Group performance status (≥1), large-cell carcinoma or not otherwise specified, and stage ≥IIIC disease. The overall 3-month mortality rate was found to have decreased significantly over the last 20 years, from 24.7% in KBP-2000 to 23.4% in KBP-2010 and 20.3% in KBP-2020 (P < 0.0001). Early mortality among patients with lung cancer has significantly decreased over the last 20 years which may reflect recent improvements in treatments. However, early mortality remained extremely high in 2020, particularly when viewed in light of improvements in longer-term survival. Delays in lung cancer diagnosis and management could contribute to this finding.

Factors Associated With Prescription of Systemic Therapy in Real-world Patients With Metastatic Renal Cell Cancer Managed in a Rural Region.

Numerous new treatment options have been approved for metastatic renal cell carcinoma (mRCC) in the last decade. Nevertheless, not all patients receive systemic therapy. Certain patients present with very advanced disease, poor Eastern Cooperative Oncology Group performance status (ECOG PS), or severe comorbidity, i.e. factors that lead oncologists to prefer best supportive care (BSC) instead of systemic therapy. The aim of this quality-of-care study was to identify baseline factors (disparities) associated with receipt of systemic therapy rather than BSC. This retrospective analysis included 140 consecutive patients managed in a rural region of Norway (2007-2022). Two differently managed groups were compared in univariate tests followed by multi-nominal regression. The majority of patients (n=95, 68%) had received systemic therapy. Typical patients were males in their 60s or 70s, with clear cell histology, prior nephrectomy, and intermediate prognostic features. Patients who received systemic therapy lived significantly longer than those who did not (median 30.4 versus 5.0 months, p<0.001). Survival benefit of systemic treatment was observed even in patients with ECOG PS3 or age ≥80 years. In addition to younger age (p<0.001) and better ECOG PS (p<0.001), metachronous presentation was associated with higher rates of systemic therapy utilization (p=0.03). Assignment to systemic therapy for mRCC was individualized in the present patient population. In all age and ECOG PS subgroups, systemic therapy was associated with better survival (doubling at least). Optimum utilization rates are difficult to determine. However, in light of the survival outcomes, a rate of 12% in patients aged 80 years or older appears rather low.

Evaluating the Prognostic Variables for Overall Survival in Patients with Metastatic Renal Cell Carcinoma: A Meta-Analysis Of 29,366 Patients

Background: Scoring systems are a method of risk assessment used to stratify patients with metastatic renal cell carcinoma (mRCC) and guide systemic therapy. The variables are weighed equally when calculating total score. However, the difference of even 1 positive predictor can change one's risk category and therapy. Objective: To compare the relative strength of association between predictive variables and overall survival (OS) in mRCC. Methods: A search of Medical Literature Analysis and Retrieval System Online (MEDLINE) and Embase was conducted. Clinical studies, retrospective and prospective, were included if the association of at least 1 predictor and OS in patients with mRCC receiving first-line systemic therapy was evaluated. Meta-analysis was performed to generate pooled hazard ratios (HRs) and 95% CIs for OS for predictors with ≥ 5 included studies. Sensitivity analysis identified outlier heterogeneity and publication bias. Results: Sixty-six studies containing 29,366 patients were included. Meta-analysis indicated lung metastases, bone metastases, thrombocytosis, time to systemic therapy &lt; 1 year, liver metastases, hypercalcemia, anemia, elevated neutrophil-lymphocyte ratio, multiple metastatic sites, neutrophilia, poor Eastern Cooperative Oncology Group (ECOG) status, no previous nephrectomy, elevated lactate dehydrogenase, Fuhrman grade 3 or 4, central nervous system metastases, elevated C-reactive protein, and Karnofsky Performance Status &lt; 80% were associated with significantly worse OS. The HRs varied from 1.34 to 2.76, representing heterogeneity in predictive strength. The effects of study heterogeneity and publication bias were minimal to moderate across all predictors. Conclusions: Based on the differences in pooled HRs, prognostic strength between the variables is likely not equivalent. Restructuring scoring models, through inclusion of other variables and usage of relative weighting, should be considered to improve accuracy of risk stratification.

Efficacy of immune checkpoint inhibitors in advanced large cell neuroendocrine carcinoma of the lung: A single‑institution experience.

Large cell neuroendocrine carcinoma (LCNEC) is a rare and highly invasive lung cancer subtype with an overall poor prognosis. Due to its low incidence rate and unusual pathological features, the clinical management of LCNEC remains controversial. The present study aimed to assess the effect of immune checkpoint inhibitors (ICIs) on treatment response and survival outcomes in patients with advanced LCNEC. The clinical data from 148 patients with LCNEC treated with ICIs at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between January 2019 and September 2021 were retrospectively analyzed. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate associations between clinicopathological variables and patient outcomes. Patients treated with ICIs demonstrated extended median overall survival (mOS) times [23.5 months; 95% confidence interval (CI), 18.524-28.476] compared with patients who did not receive ICIs (11.2 months; 95% CI, 4.530-18.930) (P<0.001). Univariate analysis revealed that histological subtype (P=0.043), lymph node metastases (P=0.032) and number of metastatic organs (P=0.009) were associated with a poor prognosis. The heterogeneity of pathological components was associated with prognosis, and the mOS time was shorter for mixed LCNEC than that for pure LCNEC (P=0.043). The median progression-free survival (mPFS) (9.78 vs. 9.37 months; P=0.82) and mOS (20.70 vs. 25.79 months; P=0.181) times showed no significant association with regard to different regimens of immuno-based combination therapy (chemotherapy combined with ICIs vs. anti-angiogenic agents combined with ICIs). Poor Eastern Cooperative Oncology Group performance status score (P=0.04), multiple organ metastases (P=0.02) and high cancer antigen 125 levels (P=0.01) were independent risk factors of a poor prognosis. The present findings offer valuable insights into potential prognostic markers and highlight the favorable impact of ICIs on OS in advanced LCNEC. Prospective clinical studies are required to validate the therapeutic value of ICIs in LCNEC.

Clinical outcomes of ROS1-positive non-small cell lung cancer with limited access to ROS1-tyrosine kinase inhibitors (TKIs): experience from an Indian tertiary referral centre.

ROS1 as a driver mutation is observed in approximately 1%-2% of all non-small cell lung cancer (NSCLC). Given its rarity, we share our experience regarding ROS1-positive NSCLC including the access to ROS1 tyrosine kinase inhibitors (TKIs) in a low-middle income country like India. It is a retrospective analysis of ROS1-positive NSCLC patients registered between January 2015 to December 2021 for demographics, treatment patterns and outcomes i.e., overall survival (OS) and progression free survival (PFS). Baseline characteristics were available for 70 patients of 78 patients positive for ROS1 by fluorescent in situ hybridisation. Median age at presentation was 52 years, 39 (55.7%) were males, most (51, 72.86%) were non-smokers and ten patients (14.3%) had poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) i.e., PS >2 at presentation. A total of 67 patients receiving cancer directed therapy were analysed for survival. The first line (1L) therapies included - ROS1 TKIs in 38, chemotherapy in 20, epidermal growth factor receptor TKI in eight and chemotherapy-bevacizumab in one only. ROS1 TKI was provided to 20 patients as part of an assistance programme. The median OS for patients who received ROS1 TKI was not attained (95% CI 37.85-NA), while it was 8.11 (95% CI 6.31-NA) months for those who did not (HR-0.1673). The median PFS for the 1L ROS1 TKI compared to the no-TKI group was 27.07 (95% CI 24.28-NA) months versus 5.78 (95% CI 3.42-12) months (HR: 0.2047). Poor ECOG PS at presentation was the only independent prognosticator for survival. Using ROS1 TKI improves clinical outcomes in all-comers though statistically not significant. To further improve outcomes, future trials should pay special attention to patients with poor PS and find a way to increase the current limited access to TKI.

Prognostic significance of pan-immune-inflammation value (PIV) in nasopharyngeal carcinoma patients

BackgroundBlood-based immune-inflammation indexes have been widely used to predict survival in a variety of cancers. In this research, we seeked to evaluate a novel immune-inflammation marker, named the pan-immune-inflammation value (PIV), in patients with nasopharyngeal carcinoma (NPC) undergoing definitive radiotherapy. MethodsA group of 377 patients with NPC was retrospectived analyzed. Clinical data and laboratory data were collected. Receiver operating characteristic (ROC) curve analysis was performed in order to determine the optimal PIV cut-off value. Survival curves were estimated by Kaplan-Meier method, and prognostic variables were identified using a Cox regression model. Additionally, we developed a nomogram and assessed its acuracy using the concordance index (C-index) and a calibration curve. ResultsThe optimal PIV cut-off value was 146.24 according to ROC analysis. High PIV was related to poorer Eastern Cooperative Oncology Group Performance Status (ECOG PS) score (p = 0.017), more advanced T (p＜0.001) and clinical stages (p = 0.024). In univariate analysis, older Age, poorer ECOG PS, higher Epstein–Barr virus DNA (EBV-DNA), advanced T, N and clinical stage, and higher PIV levels were related to patients' poorer overall survival (OS). Poorer ECOG PS, higher EBV-DNA, later T stage, later clinical stage, and higher PIV were associated with patients' poorer progression free survival (PFS). Male sex and later T stage were associated with patients' poorer locoregional recurrence free survival (LRRFS). Poorer ECOG PS, higher EBV-DNA, later T stage, later clinical stage, and higher PIV were associated with patients’ poorer distant metastasis free survival (DMFS). Multivariate analysis demonstrated that PIV was an independent prognostic index for OS (HR 2.231, 95 % CI 1.241–4.011, P = 0.007), PFS (HR 1.664, 95 % CI 1.003–2.760, P = 0.049), and DMFS(HR 2.081, 95 % CI 1.071–4.044, P = 0.031). Nomogram C-indexes for the nomogram of OS were 0.684, and PFS were 0.62, respectively. Survival predictions and actual survival were consistent according to the calibration curve. ConclusionsPre-treatment PIV is a promising biomarker for predicting survival in patients with NPC.

Safety and Efficacy of Neoadjuvant Chemotherapy for Advanced Gastric Cancer in Elderly Patients.

Elderly patients with pathological stage II/III gastric cancer struggle to complete adjuvant chemotherapy. Neoadjuvant chemotherapy (NAC) for treating locally advanced gastric cancer (LAGC) has drawn attention; however, its indication for elderly patients who are vulnerable to chemotherapy is unclear. This study aimed to investigate the feasibility and efficacy of NAC for elderly patients with gastric cancer. In this study, patients aged ≥75 years who underwent curative gastrectomy for LAGC or adenocarcinoma of the esophagogastric junction between April 2013 and November 2021 were included. Vulnerable patients, with poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2-3 were also included. The patients were classified into NAC+ (n=20) and NAC - (n=45) groups. The clinicopathological data of the patients were retrospectively investigated. The NAC+ group showed a higher R0 resection rate than the NAC- group (100% vs. 89.1%, p=0.3) and pathological downstaging was achieved in 12 (60%) cases, including five (25%) pathological complete responses. The incidence of adverse events during postoperative chemotherapy was 35%, and the rate of postoperative complications greater than Clavien-Dindo Grade II was comparable between the two groups (35% vs. 46.7%, p=0.43). The NAC+ group showed a higher three-year overall survival rate (75% vs. 36%, p=0.015). NAC was feasible and effective for elderly patients including vulnerable patients with LAGC or adenocarcinoma of the esophagogastric junction. It can be considered as treatment option, with a high down staging rate and better survival.

Evaluation of ECOG Performance Status at Diagnosis and Relapse in Patients with Acute Myeloid Leukemia

Background: Eastern Cooperative Oncology Group (ECOG) performance status (PS) is often utilized in treatment decision-making for patients with acute myeloid leukemia (AML). Patients with relapsed or refractory (R/R) disease have a particularly poor prognosis and require complex treatment decisions that utilize patient preference, genetic profile and PS. Currently, limited data exist on the trend of PS between initial diagnosis and R/R AML, and we aimed to characterize PS in R/R AML and its association with short and long term survival. Methods: We utilized an institutional database from the University of Washington/ Fred Hutchinson Cancer Center to retrospectively identify a subset of patients with AML or other high-grade myeloid neoplasms (≥10% blasts in blood or marrow at diagnosis) who received both induction and salvage chemotherapy for first relapse between January 1, 2008 and December 1, 2021. Salvage treatment was divided into high intensity (cytarabine greater than 1g/m 2/dose), intermediate intensity (7+3 or similar), reduced intensity (i.e., hypomethylating agents) or other (investigational agents not fitting into prior categories or supportive care alone). The McNemar test was used for matched-pair analysis of PS at two timepoints. The Kaplan-Meier method was used for analysis of overall survival (OS). Multivariable regression was used to evaluate associations with 4 week survival. Multivariable Cox regression was used for analysis of overall survival. All statistical analyses were performed using R 4.2.1 (2022). Results: We identified 160 patients with R/R disease. Patients with missing PS data (n=33) or otherwise not meeting inclusion criteria (n=20) were excluded (baseline characteristics of 107 patients in Table 1). No significant change was identified in PS at initial diagnosis versus R/R (PS≤1 71% vs 63%, p=0.19). More patients had the same PS at R/R disease (51.4%) as compared to initial diagnosis, though some had worse PS (27.1%), and others had better PS (25.2%). At initial diagnosis, patients with poor PS had similar induction chemotherapy intensity to those with good PS (PS≤1 treatment intensity: high: 42.1%, intermediate: 34.2%, reduced: 23.7%, other: 0%; PS≥2 treatment intensity: high: 38.7%, intermediate: 32.2%, reduced: 25.8%, other: 3.2% (p=0.55). At R/R disease, patients with poor PS were more likely to receive less intensive therapy (PS≤1 treatment intensity: high: 52.2%, intermediate:14.9%, reduced: 14.9%, other: 17.9%; PS≥2 treatment intensity: high: 27.5%, intermediate:7.5%, reduced:32.5%, other: 32.5% (p=0.001)). There was no correlation between PS at R/R disease and rate of complete remission without measurable residual disease (PS≤1 = 26.8%, PS≥2 =20%, p=0.49) or treatment failure (PS≤1 = 38.8%, PS≥2 =35%, p=0.84). The 4-week unadjusted mortality rate at R/R was 10.4% for patients with PS≤1, and 25.6% for patients with PS ≥2 (p=0.04). OS was longer in patients with good PS (PS≤1) at R/R disease (8.9 months vs 3.0 months). In multivariate analysis, poor ECOG (HR 2.13, 95% CI 1.09-4.17) was correlated with worse OS, while favorable ELN score (HR 0.43, 95% CI 0.19-0.99) and transplant (HR 0.29, 95% CI 0.17-0.49) were associated with improved OS. We did not find a significant association between age, gender, secondary status, or change in PS and OS in our preliminary analysis. Conclusions: We did not identify a significant change in PS in R/R disease. Our preliminary results suggest that poor PS at R/R was correlated with an increased 4-week mortality rate and worse OS. Interestingly, we did not find a significant difference in treatment intensity for patients with poor PS at initial presentation. In addition, at R/R disease, patients with good and poor PS had similar rates of treatment failure despite patients with good PS being treated with more intensive regimens. A limitation of our work is possible selection bias, as patients with significant functional decline may not have returned for evaluation at R/R disease. Further work is needed to identify if there is a meaningful association between change in PS and outcomes at R/R disease.

Baseline characteristics may impact treatment duration of cabazitaxel in patients with mCRPC: a subanalysis of data from a post-marketing surveillance.

Cabazitaxel has demonstrated improvements in overall survival among patients with metastatic castration-resistant prostate cancer (mCRPC) in the pivotal comparison clinical trials TROPIC, PROSELICA and CARD. However, these trials include mCRPC patients with similar characteristics, and there are limited data on how baseline characteristics affect treatment discontinuation in the patient population. To assess individual factors that may impact the discontinuation rate of cabazitaxel treatment, we conducted a post hoc analysis of data from a nationwide all-case, post-marketing surveillance of cabazitaxel in Japan. Patients were grouped according to the number of cabazitaxel treatment cycles received (1-2 and≥3cycles). Predictive factors were identified through multivariate logistic regression analysis. Across 660 patients with metastatic castration-resistant prostate cancer, 70.2% received ≥3cycles of cabazitaxel treatment. Those receiving 1-2cycles of cabazitaxel had a greater proportion of patients with poorer Eastern Cooperative Oncology Group Performance Status, presence of lung and liver metastases, higher prostate-specific antigen level and prior radiation therapy at baseline. Regardless of the number of cabazitaxel cycles received, the primary reason for discontinuation was progression of disease rather than adverse events. Compared with those receiving 1-2cycles, a lower proportion of patients receiving 3-10 and≥11cycles of cabazitaxel treatment experienced adverse events. Multivariate analysis showed a significant association between early discontinuation and presence of liver lesions, poorer Eastern Cooperative Oncology Group Performance Status and higher prostate-specific antigen level at baseline. Post-marketing surveillance data suggest physicians should individualize cabazitaxel treatment based on certain patient characteristics at baseline.

Real-world analysis of ruxolitinib in myelofibrosis: interim results focusing on patients who were naïve to JAK inhibitor therapy treated within the JAKoMo non-interventional, phase IV trial

Ruxolitinib (RUX) is a Janus kinase 1/2 inhibitor (JAKi) approved in the EU for treating disease‑related splenomegaly or symptoms in adults patients with myelofibrosis (MF). This is an interim analysis of JAKoMo, a prospective, non‑interventional, phase IV study in MF. Between 2012–2019 (cutoff March 2021), 928 patients (JAKi-naïve and -pretreated) enrolled from 122 German centers. This analysis focuses on JAKi-naïve patients. RUX was administered according to the Summary of Product Characteristics. Compared to the COMFORT-I, -II, and JUMP trials, patients in JAKoMo were older (median 73 years), had poorer Eastern Cooperative Oncology Group (ECOG) performance statuses (16.5% had ECOG ≥ 2), and were more transfusion dependent (48.5%). JAKoMo represents the more challenging patients with MF encountered outside of interventional studies. However, patients with low-risk International Prognostic Scoring System (IPSS) scores or without palpable splenomegaly were also included. Following RUX treatment, 82.5% of patients experienced rapid (≤ 1 month), significant decreases in palpable spleen size, which remained durable for 24 months (60% patients). Symptom assessment scores improved significantly in Month 1 (median –5.2) up to Month 12 (–6.2). Common adverse events (AEs) were anemia (31.2%) and thrombocytopenia (28.6%). At cutoff, 54.3% of patients had terminated the study due to, death, AEs, or deterioration of health. No new safety signals were observed. Interim analysis of the JAKoMo study confirms RUX safety and efficacy in a representative cohort of real-world, elderly, JAKi-naïve patients with MF. Risk scores were used in less than half of the patients to initiate RUX treatment.Trial registration: NCT05044026; September 14, 2021.

Anemia Profiles in Cancer Patients: Prevalence, Contributing Factors, and Insights From a Retrospective Study at a Single Cancer Center in Saudi Arabia.

Anemia, a common complication of cancer and its treatments, significantly affects cancer patients' survival and quality of life. Nevertheless, there is limited research conducted in the southern region of Saudi Arabia regarding its effects. This study aims to assess the prevalence of anemia, as well as its associated factors, among cancer patients undergoing active chemotherapy treatment. This retrospective study analyzed adult cancer patients who underwent chemotherapy at King Khaled Hospital's oncology department in Najran, Saudi Arabia, between 2017 and 2022. We aimed to determine the prevalence and contributing factors of anemia through comprehensive demographic and clinical assessment. Univariate analysis was performed to assess factors necessitating blood transfusion. A total of 95 cancer patients received chemotherapy, with a mean age of 52.2 ± 16.5 years. The majority were females (65.3%) aged between 18 and 64 years (74.7%). Gastrointestinal (42.1%) and breast (17.9%) cancers were the most prevalent malignancies. Most patients (56.8%) were in locally advanced stages. Anemia was present at admission in 48 (50.5%) patients with a higher prevalence among colorectal and genitourinary tract cancer patients. The mean hemoglobin (Hb) drop during treatment was 9.1 ± 2.1 g/dL. Anemia severity was stratified as follows: life-threatening (7.4%), severe (33%), moderate (31%), and lower limited (29%). Blood transfusions were required in 79% of cases. Advanced age, increased chemotherapy cycles, and anemia of chronic disease (ACD) were significantly associated with increased anemia severity (p<0.05). Increasing chemotherapy cycles also correlated with an increased need for blood transfusion (p<0.001). Older patients (≥65 years) had higher anemia at admission, poor Eastern Cooperative Oncology Group (ECOG) performance status, more Hb decrease during treatment, and increased need for blood transfusions (p<0.05) compared to younger patients (<65 years). The study noted a high prevalence of anemia (50.5%) in patients receiving active cancer treatment, specifically in the context of genitourinary and gastrointestinal tract cancers. Advanced age, frequent chemotherapy cycles, and ACD were associated with increased severity of anemia. Furthermore, older patients displayed a higher frequency of anemia, poorer performance status, and an increased requirement for transfusions with an escalating number of chemotherapy cycles.

Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis.

Recently, many studies have explored the relationship between the expression of programmed death ligand 1 (PD-L1) and prognosis in gastric cancer, but there is still controversy. Additionally, few studies have specifically investigated the expression of PD-L1 in patients with peritoneal metastasis. Immunohistochemistry was used to analyze the expression of PD-L1 in gastric cancer patients with peritoneal metastasis. The combined positive score (CPS) was calculated to evaluate the expression of PD-L1, and the clinicopathological data were analyzed to explore prognostic significance. In total, 147 gastric cancer patients with peritoneal metastasis were enrolled. The negative PD-L1 expression was defined as a CPS < 1, and high PD-L1 expression was defined as a CPS ≥ 10. PD-L1 expression with CPS ≥ 1 and CPS-negative was detected in 67 (45.58%) and 80 (54.42%) patients, respectively. High PD-L1 expression at PD-L1 CPS ≥ 10 was detected in 21(14.29%) patients. The median overall survival (OS) was 18.53 months in the CPS < 10 group and 27.00 months in the CPS ≥ 10 group; the OS difference between the two groups was significant (p = 0.015). Multivariate analysis demonstrated that a poor Eastern Cooperative Oncology Group performance score (ECOG PS) (p = 0.002) and severe peritoneal metastasis (p = 0.033) were significantly associated with poor survival, while palliative chemotherapy (p = 0.002) and high PD-L1 expression (p = 0.008) were independent and significantly favorable prognostic factors. Our study demonstrated that PD-L1 expression was widely presented in gastric cancer patients with peritoneal metastasis, while a CPS no less than 10 predicted better prognosis.