Poor Eastern Cooperative Oncology Group Research Articles

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.

One-Year Survival and Prognosticators of Adults With Acute Leukemia at the Uganda Cancer Institute.

Acute leukemias are associated with substantial morbidity and mortality, particularly in the adult population. Despite an increasing burden of acute leukemia in developing countries, there are limited data on clinical outcomes and prognostic factors in this setting. In this study, we aimed to describe the clinical characteristics, survival, and prognostic factors of adults with acute leukemia at the Uganda Cancer Institute (UCI). A retrospective cohort study was conducted between January 2009 and December 2018, reviewing data of patients 18 years or older with a cytopathologic diagnosis of acute leukemia at UCI. Data were extracted on clinical and laboratory characteristics, response to treatment, and survival. Cox-proportional hazards regression and survival analysis were performed to determine survival rates and associated factors. P < .05 was considered statistically significant. In total, 233 participants were enrolled. Most (59.2%. n = 138) participants were male, with a median age of 32 years (IQR, 23-48 years), and 136 (58.4%) had AML. Overall, the 1-year survival was 16.5%, with a median survival time of 47 (IQR, 21-219) days. Predictors of mortality were being a female (adjusted hazard ratio [aHR], 2.8; 95% CI, 1.2 to 6.7; P = .022) and overweight (aHR, 4.2; 95% CI, 1.3 to 13.4; P = .015). Among the patients who had AML, the predictors were poor Eastern Cooperative Oncology Group (ECOG; aHR, 3.1; 95% CI, 1.6 to 6.2; P = .001) and HIV (aHR, 6.0; 95% CI, 1.7 to 20.5; P = .004). Among the patients who had ALL, the predictors were poor ECOG (aHR, 2.3; 95% CI, 1.3 to 4.1; P = .006). Patients with acute leukemia in Uganda have poor overall survival. Prospective studies are recommended to better understand causes of early mortality.

Clinical predictors and outcomes of non-expandable lung following percutaneous catheter drainage in lung cancer patients with malignant pleural effusion.

Non-expandable lung (NEL) often occurs during pleural fluid drainage in patients with malignant pleural effusion (MPE). However, data regarding the predictors and prognostic impact of NEL on primary lung cancer patients with MPE receiving pleural fluid drainage, compared to malignant pleural mesothelioma (MPM), are limited. This study was aimed to investigate the clinical characteristics of lung cancer patients with MPE developing NEL following ultrasonography (USG)-guided percutaneous catheter drainage (PCD) and compare the clinical outcomes between those with and without NEL. Clinical, laboratory, pleural fluid, and radiologic data and survival outcomes of lung cancer patients with MPE undergoing USG-guided PCD were retrospectively reviewed and compared between those with and without NEL. Among 121 primary lung cancer patients with MPE undergoing PCD, NEL occurred in 25 (21%). Higher pleural fluid lactate dehydrogenase (LDH) levels and presence of endobronchial lesions were associated with development of NEL. The median time to catheter removal was significantly extended in those with NEL compared to those without (P = .014). NEL was significantly associated with poor survival outcome in lung cancer patients with MPE undergoing PCD, along with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), the presence of distant metastasis, higher serum C-reactive protein (CRP) levels, and not receiving chemotherapy. NEL developed in one-fifth of lung cancer patients undergoing PCD for MPE and was associated with high pleural fluid LDH levels and the presence of endobronchial lesions. NEL may negatively affect overall survival in lung cancer patients with MPE receiving PCD.

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.

Survival with lung cancer in Finland has not improved during 2007–2019–a single center retrospective population-based real-world study

Objectives According to the CONCORD-3 study, the 5-year survival rate of lung cancer patients in Finland has not improved during the twenty-first century. In the present study, we evaluated the survival trends of lung cancer patients diagnosed and treated in one of the five university hospitals in Finland to determine possible explanatory factors behind the lack of improved survival. Material and methods This retrospective population-based study included all lung cancer patients diagnosed in Tampere University Hospital in 2007–2019 (N = 3041). The study population was divided into two subcohorts: the patients diagnosed in 2007–2012 and those diagnosed in 2013–2019. The two subcohorts were then compared to analyze the temporal changes in survival and the distribution of prognostic factors. Results A comparison of the patients diagnosed in 2007–2012 and 2013–2019 showed that the patients’ overall survival had remained unchanged. The median overall survival was 8.7 months in the earlier subcohort and 9.2 months in the later subcohort. The respective 5-year survival rates were 16.6% and 17.8%, and these differences were not statistically significant. The proportion of stage IV patients (approximately 59% in both subcohorts) and their risk of death were similar for the two subcohorts. According to the regression analysis, male gender, advanced stage, and poor Eastern Cooperative Oncology Group performance status were independent risk factors for death, while a never-smoking status and mutation-positive disease were associated with a decreased risk of death, but only in the later cohort. Conclusion Echoing the results of CONCORD-3, this study confirmed that the real-world survival of unselected lung cancer populations in Finland has not improved over the last 15 years, mainly because of the unchanged proportions of patients with late-stage lung cancer. This calls for earlier recognition of lung cancer, achieved by screening and increasing awareness of the disease.

Long-Term Results with Thiotepa-Containing Conditioning Regimens for Autologous Stem Cell Transplantation

Autologous stem cell transplantation (ASCT) remains a cornerstone in the treatment of both Hodgkin lymphoma (HL) and various non-Hodgkin lymphoma (NHL) subtypes. BEAM (carmustine, etoposide, cytarabine, and melphalan) is the most frequently used conditioning regimen; however, owing due to limited availability and toxicity of carmustine, thiotepa-containing regimens have been suggested. We previously reported encouraging results in ASCT with a TECAM (thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan) conditioning regimen from 2000 to 2013. We aimed to update our experience with the TECAM regimen by adding our experience from 2013 to 2020 to the previously reported cohort. Moreover, we aimed to use the detailed data for the 2 transplant cohorts to identify improvements in ASCT outcomes in the recent era. We retrospectively analyzed all lymphoma patients who underwent ASCT at our center between January 2000 and December 2020. A total of 353 lymphoma patients were included (142 in the newer cohort added to 211 previously reported patients), all of whom were treated with our standard TECAM conditioning regimen. The cohort included 127 patients with HL, 107 with DLBCL, and 119 with other NHL subtypes. The newer cohort was characterized by significantly poorer Eastern Cooperative Oncology Group Performance Status (ECOG-PS) prior to ASCT (45.7% versus 19.3% with ECOG-PS ≥1; P < .01), whereas a higher proportion of patients entered transplantation in complete response (CR) (71.9% versus 47.8%; P < .01). The median follow-up after ASCT was 136.4 months (95% confidence interval [CI], 91.4 to 181.4 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates post-ASCT for the entire cohort were 59.8% and 79.3%, respectively. Evaluating the 303 of 353 patients (86.4%) who entered ASCT with a responsive disease-a population that represents today's approach to the selection of patients for ASCT-the 3-year PFS and OS rates were 61.5% and 81.9%, respectively. In this population, the 3-year PFS rate was 62.2% for HL, 62.6% for DLBCL, 64.3% for primary central nervous system lymphoma (PCNSL), and the 3-year OS rate were 90.1%, 75.2%, and 78.6%, respectively. OS was significantly better in the newer cohort (P < .01), but not when evaluating only patients who entered ASCT with responsive disease. Dose reductions, poor disease status, and poor ECOG-PS at ASCT entry were associated with worse outcomes across all lymphoma subtypes. In accordance with our previous report, patients entering transplantation for DLBCL with a partial response achieved similar outcomes as those with a CR. Eighteen patients died within the first 100 days, 8 due to disease progression and 10 due to transplantation-related complications (2.8%). There were no cases of interstitial pneumonitis syndrome. Twenty-two cases (6.2%) of secondary malignancies were documented. Our results confirm that TECAM is an effective and safe conditioning regimen for ASCT in patients with HL and various NHLs, including favorable results in PCNSL. Despite a higher proportion of frail patients, the newer cohort's outcomes were favorable, driven by better lymphoma control pretransplantation. In the DLBCL cohort, ECOG-PS had more prognostic value than achieving a CR pre-ASCT, a finding relevant to the optimal allocation of patients to different treatment options in the era of chimeric antigen receptor T cell availability.

Real-world clinical outcomes of nivolumab and taxane as a second- or later-line therapy for recurrent or unresectable advanced esophageal squamous cell carcinoma.

Nivolumab is approved in Japan as a second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC) resistant to fluoropyrimidine and platinum-based drugs. It is also used in adjuvant and primary postoperative therapies. This study aimed to report real-world data on nivolumab use for esophageal cancer treatment. In total, 171 patients with recurrent or unresectable advanced ESCC who received nivolumab (n = 61) or taxane (n = 110) were included. We collected real-world data of patients treated with nivolumab as a second- or later-line therapy and evaluated treatment outcomes and safety. Median overall survival was longer and progression-free survival (PFS) was significantly longer (p = 0.0172) in patients who received nivolumab than in patients who received taxane as a second- or later-line therapy. Furthermore, subgroup analysis for second-line treatment only showed the superiority of nivolumab in increasing the PFS rate (p = 0.0056). No serious adverse events were observed. In real-world practice, nivolumab was safer and more effective than taxane in patients with ESCC with diverse clinical profiles who did not meet trial eligibility criteria, including those with poor Eastern Cooperative Oncology Group performance status, comorbidities, and receiving multiple treatments.

Brain Metastases, Large Cell Neuroendocrine Carcinomas and Prognosis

Objective: Pulmonary large cell neuroendocrine carcinomas (LNECs) are not common but brain metastases are common in LNEC patients. Because of their rarity, there are no randomized controlled trials on optimal treatment. Generally available data are based on case reports and retrospective studies. For this reason, we retrospectively analyzed patients with LNEC that we followed up for brain metastases to contribute to the literature.&#x0D; Methods: Between 2009 and 2020, 38 patients with brain metastases diagnosed with LNEC in our center were reviewed retrospectively.&#x0D; Results: 38 patients were evaluated. The mean survival time was 5.17 months (95% confidence interval (CI) : 3.17-7.13). In multivariate analysis showed us that; shorter overal survival is associated with age (p=0.001), uncontrol of primary cancer (p=0.014), presence of metachronous metastases (p=0.003), poor Eastern Cooperative Oncology Group (ECOG) performance score (p=0.025), and high uric acid level (p=0.001) and high lactate dehydrogenase (LDH) levels (p=0.009).&#x0D; Conclusion: LNECs are rare but aggressive cancers. LNECs often metastasize to the brain. According to our study, high LDH, high uric acid, poor ECOG performance score, ≥65 years, metachronous metastasis, uncontrolled primary tumor are associated poor prognosis. LDH, uric acid, age, presence of metachron metastasis, controbility of primary tumor can be used as easy and inexpensive biomarkers to determine the prognosis and in the follow-up and treatment of patients with LNECs with brain metastases as metastases seen of other cancers.

Population-based Long-term Outcomes for Squamous Cell Carcinoma of the Nasal Cavity.

This study evaluates population-based outcomes of patients with squamous cell carcinoma (SCC) of the nasal cavity treated in British Columbia. A retrospective review of nasal cavity SCC treated from 1984 to 2014 was performed (n = 159). Locoregional recurrence (LRR) and overall survival (OS) were evaluated. The 3-year OS was 74.2% for radiation alone, 75.8% for surgery alone, and 78.4% for surgery and radiation ( P = 0.16). The 3-year LRR was 28.4% for radiation alone, 28.2% for surgery alone, and 22.6% for surgery and radiation ( P = 0.21). On multivariable analysis, surgery and postoperative radiation relative to surgery alone was associated with a lower risk of LRR (hazard ratio: 0.36, P = 0.03). Poor Eastern Cooperative Oncology Group status, node-positive, orbital invasion, smoking, and advanced age were associated with worse OS (all P <0.05). In this population-based analysis, multimodality treatment with surgery and adjuvant radiation were associated with improved locoregional control for SCC of the nasal cavity.

First-line Chemotherapy Response Is Associated With Clinical Outcome During Immune Checkpoint Inhibitor Treatment in Advanced Urothelial Carcinoma: A Real World Retrospective Study.

Immune checkpoint inhibitors (ICI) have become important tools for the treatment of advanced urothelial carcinoma (aUC). However, the clinical strategy using ICIs and chemotherapy is still controversial. The aim of this study was to evaluate the association of clinical parameters in aUC patients with ICI treatment. We retrospectively analyzed aUC patients who received atezolizumab and pembrolizumab between January 2015 and October 2020. The associations between baseline demographics and clinical outcomes were evaluated. Of the 74 included patients, the median age was 67 years. Among them, 53 patients received atezolizumab and 21 received pembrolizumab. There were 50 patients receiving first line ICIs therapy and 24 receiving second line monotherapy. Fifty-two (83.87%, 52/62) received cisplatin among all chemotherapy patients. The median progression free survival was 10.94 months, and the overall survival was 28.44 months. Poor chemotherapy response or no chemotherapy, liver metastases, Eastern Cooperative Oncology Group (ECOG) status and higher neutrophil/lymphocyte ratio (NLR) were associated with higher risk of disease progression (HR=5.70, 95% CI=2.04-15.90, p=0.001; HR=6.08, 95% CI=1.79-20.57, p=0.004; HR=5.40, 95% CI=1.76-16.57, p=0.003; HR=6.08, 95% CI=2.56-14.44, p<0.001 and HR=1.02, 95% CI=1.01-1.03, p=0.002, respectively). Liver metastases and WBC before ICI were associated with increased risk of death (HR=11.95, 95% CI=3.22-44.34, p<0.001; HR=1.0001, 95%=CI=1.00001-1.00002, p=0.036 respectively) while ICI response was associated with decreased death (HR=0.22, 95%CI=0.08-0.62, p=0.004). Chemotherapy response was associated with better ICI treatment response (OR=6.52, 95% CI=1.45-29.24, p=0.014) while lymph node metastases and poor ECOG status were associated with poor ICI response (OR=0.31, 95% CI=0.10-0.94, p=0.038; OR=0.32, 95% CI=0.11-0.95, p=0.040). Our real-world data show a predictive role of first-line chemotherapy response to ICI treatment efficacy in aUC patients as well as other prognostic factors, such as ECOG status, serum WBC or NLR and liver metastases.