Difference In Median Survival Research Articles

Exploration of Language As a Barrier to the Assessment and Management of CAR T-Cell Therapy Associated Toxicities

Introduction: Chimeric antigen receptor T-cell therapy (CAR T) is a novel therapy associated with a unique toxicity profile, namely cytokine release syndrome (CRS) occurring in (37-93%) of patients (pts) and immune effector cell associated neurotoxicity (ICANS) occurring in 23-67% of pts [Zahid, 2020]. Grading and management of these toxicities varies amongst institutions and patient populations. Furthermore, assessment of ICANS utilizes the Immune Effector Cell-Associated Encephalopathy (ICE) scoring system which includes 5-components that are dependent on a patient's English- speaking proficiency [Lee 2019]. We previously reported a higher-grade of neurotoxicity assessed in non-English speaking pts in a cohort of 127 pts at our institution [Melody, 2023]. We sought to confirm our previous findings by analyzing the impact of language spoken on the incidence, severity, and management including resource utilization for CAR T associated toxicities, in a larger multi-institutional cohort. Methods: We compiled retrospective data from 13 academic institutions for pts with aggressive B-cell lymphoma treated with CD-19 directed CAR T between 2015 through 2022. Baseline characteristics, lymphoma treatment, along with incidence, severity and management patterns of CRS and ICANS were compared between non-native English-speaking (NNES) and native-English speaking (ES) pts with Pearson Chi-squared test. OS was estimated via Kaplan-Meier method. Results: In a cohort of 582 pts treated with CAR T, 555 pts were ES and 27 were NNES pts; 17= Spanish, 3= Cantonese, 7= other (including Arabic, Burmese, Polish, Igbo, Japanese, Korean, & Mandarin). Demographic and clinical data for NNES and ES cohorts are included in Table 1. There was no difference in baseline disease characteristics between the two pt populations with the exception of younger pts and a higher proportion of women in the NNES group (p =0.02). Translator services were utilized for 20 (74%) of NNES pts at any point during CAR T-cell treatment. Two-thirds (66.7%) of NNES pts developed CRS (4=grade 0, 6= grade 1, 9= grade 2, 1= grade 3, 2 =grade 4, 5=Missing data) vs 55.5% of ES pts developed CRS (63=grade 0, 131= grade 1, 134= grade 2, 56= grade 3, 1 =grade 4, 1=grade 5, missing= 169), p < 0.001. For CRS management, there was no difference in the use of tocilizumab (48.1% vs 46.0%, p= 0.85) or escalation to ICU care (13.3% vs 10.1%, p= 0.66) for NNES vs ES groups, respectively. Thirty-seven percent of NNES pts developed ICANS (6=grade 0, 4= grade 1, 2= grade 2, 3= grade 3, 1=grade 4, 11=missing) compared with 39.8% of ES pts who developed ICANS (120=grade 0, 75= grade 1, 60= grade 2, 75= grade 3, 8= grade 4, 3= grade 5, missing= 241), p= 0.92. ICE scoring for ICANS assessment was recorded in 48% and 51% of NNES and ES pts, respectively. For management of ICANS, there was no difference in the use of steroids (51.9% vs 43.4%, p= 0.43), lamotrigine (61.5% vs 46.0%, p=0.39), or anakinra (10% vs 11.7%, p= 1.0) between NNES vs ES pts. There was no difference in escalation to ICU care for management of ICANS between groups (15.4% vs 19.1%, p=1.0). Neurology consults were obtained more frequently for NNES vs ES but this difference was not statistically significant (61.5% vs 40.5% respectively, p=0.16). Similarly, neuroimaging was obtained more frequently in NNES vs ES pts though not statistically significant (69.2% vs 53.4% respectively, p= 0.39). There was no difference between re-admission rates within 90 days post CAR T for NNES and ES pts (34.6% vs 26%, p = 0.36). With median follow-up of 35.3 mo (1.4-82.9), there was also no statistical difference in median overall survival of 17.8 mo in NNES pts compared to 28.9 mo in ES pts (p= 0.50; Figure 1). Conclusions: Despite our previous observations of increased severity of CRS and ICANS in NNES pts at our own institution, expansion to a larger multi-institutional cohort did not identify differences in occurrence, assessment, or management of toxicities between NNES and ES pts. Analyses were limited by small sample size of NNES patients and missing data for our patient cohort as a whole. This may be explained by decreased access to tertiary care for CAR T in NNES pts and highlights the lack of standardization in assessment and management of CRS/ICANS more globally. None-the-less, the assessment of language as a barrier to care warrants further exploration as does validation of current ICANS assessment tools in NNES pts.

Study on the comparison of postoperative liver injury caused by hepatic arterial perfusion chemotherapy combined with targeted immunotherapy with hepatic arterial chemoembolization combined with targeted immunotherapy for intermediate-and advanced-stage liver cancer

Objective: To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs). Methods: Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ(2) test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results: This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ(2)=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ(2)=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ(2)=20.298, P < 0.001, 54.9% vs. 85.7%, χ(2)=17.917, P < 0.001;40.2% vs. 55.8%, χ(2)=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ(2)=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion: The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.

Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care. We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to 581 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features. We discovered that the serum white blood cell (WBC) count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of WBC count. By utilizing an objective PD-L1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PD-L1 expression in glioblastoma patients with high serum WBC counts. These findings suggest that in a subset of glioblastoma patients the incorporation of WBC count and PD-L1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, machine learning models allow the distillation of complex clinical data sets to uncover novel and meaningful clinical relationships.

Combined hepatic resection and ablation for high burden of colorectal liver metastases demonstrates safety and durable survival

BackgroundHepatic resection (HR) and thermal ablation of Colorectal Liver Metastases (CRLM) have each individually demonstrated safety and survival benefit. We sought to provide our experience with the combination of HR + ablation within one operation for patients with multiple CRLM. MethodsReview of a single institution database of patients who underwent HR + ablation between 2010 and 2019. Results161 patients were identified who underwent HR + ablation for isolated CRLM (mean age: 59, male 63.4%). 125 (77.6%) patients had bilobar disease and 92 (57.1%) patients had ≥5 tumors. 28 (17.4%) patients experienced minor (grade 1 or 2) complications while 20 (12.4%) had grade 3–5 complications. Patients who underwent simultaneous colon resection with HR + ablation had a higher complication rate (22 of 47, 46.8%) than those undergoing HR + ablation only (26 of 114, 22.8%, p = 0.002). Median and 5-year OS for all patients undergoing HR + ablation was 38.2 months and 33.2%, respectively. 5-year hepatic recurrence free survival was 23.5%. Patients with 5 or more tumors demonstrated no difference in median survival compared to those with fewer than 5 tumors (37.0 months vs 38.4 months, p = 0.326). ConclusionsIn this population of CRLM patients with a relatively high burden of disease, HR + ablation demonstrated an acceptable safety profile as well as durable long-term survival.

Outcomes of Patients Receiving Intensive Therapy for Acute Myeloid Leukemia Relapsed after/Refractory to Frontline Less-Intensive Therapy

Background: Hypomethylating agent (HMA) and venetoclax (Ven) frontline therapy for acute myeloid leukemia (AML) is astandard of care for patients (pts) deemed to be poor candidates for intensive induction due to age or fitness. However, given its attractive risk-benefit ratio, there is an increasing interest to extend the preference for HMA + Ven to other pts, including those who are fit for intensive therapy but with adverse risk disease. Unfortunately, most pts treated in this fashion will require future therapies for relapsed/refractory (R/R) disease and intensive therapy is given consideration mostly for pts with a path to allogeneic hematopoietic stem cell transplantation (alloHCT). Little is known about the outcomes of pts who receive intensive induction therapy after use of a frontline less-intensive regimen in the modern era. In this multi-center study, we seek to describe the experience with such a patient population and identify predictors of differential clinical outcomes. Methods: We conducted a multi-center, retrospective study of pts with AML treated with frontline less-intensive chemotherapy, followed by intensive induction chemotherapy for R/R disease. We first described the baseline characteristics of this cohort. Nominal variables were summarized with frequency and percentage while continuous variables were summarized with median and interquartile range (IQR). Overall response rate (ORR) was defined as complete remission (CR), complete remission with incomplete count recovery, or morphologic leukemia free state. Differences in ORR were analyzed with Fisher's exact test for nominal variables and Wilcoxon rank-sum test was used for continuous variables. Kaplan-Meier analysis was used to determine median overall survival (OS) after induction chemotherapy. Log-rank testing and Cox proportional hazard models were used to determine survival differences for nominal and continuous variables, respectively. Statistical significance was determined as p-value &amp;lt;0.05. Results: A total of 23 pts were included in this study. Median age at diagnosis was 64 years (IQR: 62-71). The majority of pts were male (n=12, 52%), white (n=20, 87%), and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 (n=18, 82%). The majority of pts (61%) at time of frontline therapy had AML arising out of MDS. As expected, the majority of pts had adverse risk ELN cytogenetics (n=16, 70%) with an enrichment for disease harboring TP53 mutation (n=6, 27%) and complex karyotype (n=9, 39%). Fifteen pts (65%) had frontline therapy with azacitidine backbone, 6 pts (26%) with decitabine; some pts received both before intensive therapy. The median number of cycles of frontline therapy was 2 (IQR: 2-5). Median WBC at time of R/R therapy was 1.9 x 10 9/L (IQR: 0.8-6.45), while hemoglobin was 8.4 g/dL (IQR: 7.5-9.45), platelets were 41 x 10 9/L (IQR: 19.5-116.5), and marrow blasts were 25% (IQR: 16.5-30%). The plurality of pts received CPX-351 as intensive R/R therapy (n=9, 39%). Other regimens included 7+3 (n=2, 9%), FLAG-Ida + Ven (n=2, 9%), HiDAC + Mitoxantrone +/- Ven (n=4, 17%) ( Table 1). ORR after intensive R/R therapy was 27% (n=6), with 23% achieving CR. CPX-351 after HMA + Ven was specifically associated with an ORR of 33% (CR rate 22%). Median OS after initiation was 5.8 months. Thirty- and 60-day mortality was 17% and 26%, respectively. Five patients (23%) proceeded to alloHCT ( Table 1). Univariate differences in response rate and median survival were analyzed for each of the aforementioned variables as illustrated in Table 1. While none of the covariates reached statistical significance for impacting ORR or OS, ECOG PS trended towards significantly impacting OS ( p=0.074) and the median OS among patients proceeding to alloHCT was numerically doubled (8.0 vs. 4.0 months, p=0.11) ( Figure 1). Conclusions: Intensive therapy for R/R AML after prior frontline less-intensive therapy was associated with an ORR rate of 27% and median OS of 5.8 months in our cohort. This approach may be an appropriate strategy for a subset of pts, particularly those eligible for alloHCT. The relatively small and heterogeneous nature of this cohort limits strong conclusions regarding efficacy. As the use of frontline HMA + Ven continues to expand, further studies with larger sample size are needed to determine which pts would and would not benefit from intensive induction therapy in the R/R setting.

Impact of Initial Timing of Metastatic Disease on Survival in Patients With Newly Diagnosed Metastatic Castration-Resistant Prostate Cancer Treated With Androgen Receptor Pathway Inhibitors.

Patients with synchronous (de novo) metastatic castration-sensitive prostate cancer appear to have worse survival outcomes and shorter time to develop castration resistance than patients with metachronous disease. However, the impact of synchronous metastasis on outcomes in metastatic castration-resistant prostate cancer (mCRPC) setting is unknown in patients without prior exposure to androgen receptor pathway inhibitors (ARPIs). In this study, we assessed the impact of initial timing of metastasis (synchronous vs metachronous) on survival outcomes of patients with new-onset mCRPC in a real-world population treated with first-line abiraterone or enzalutamide. Data were collected retrospectively from 323 patients with a confirmed diagnosis of mCRPC who received ARPIs as first-line therapy and had no prior exposure to ARPIs. The study endpoints were progression-free survival and overall survival. The results showed that median overall survival was significantly shorter in patients with synchronous disease than those with metachronous disease (26 vs 38.7 months, HR 1.42, 95% CI 1.09-1.86, P = .011). However, there was no difference in median progression-free survival. The initial presentation with synchronous metastasis remained an independent factor associated with shorter OS in the multivariable analysis. These hypothesis-generating data, after external validation, may have implications in patient counseling, prognostication, and design of future clinical trials in the new-onset mCRPC setting.

Re-Evaluating Chemotherapy Dosing Strategies for Ovarian Cancer: Impact of Sarcopenia.

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.

Disparities in Pancreatic Cancer Outcomes in the Disaggregated Asian American Population.

The Asian American, Native Hawaiian, and Pacific Islander (AANHPI) population is among the fastest-growing population in the USA. However, this is not reflected in scientific research, in which ethnic groups are often combined. We identified trends in treatment and outcomes for pancreatic cancer in a disaggregated AANHPI population. We hypothesize that patients from different AANHPI groups have differences in survival. A retrospective analysis of the National Cancer Database between 2010 and 2019 identified patients treated for pancreatic cancer. We identified demographic factors for patients of Caucasian, African American, and disaggregated Asian subpopulations. Survival curves were generated and multivariate analysis was performed to help determine which factors impacted overall survival. A total of 296,448 patients met the inclusion criteria. Of those, 8568 (3%) patients were Asian. Median survival of AANHPI patients was 11.3 months, as compared with Caucasians (8.9 months) and African Americans (8.1 months) (p<0.0001). Asian Indians had the highest median survival (14.3 months), whereas the Japanese subpopulation had the lowest (7.6 months) (p<0.0001). There were significant differences in median survival between the different AANHPI subpopulations irrespective of stage. Multivariate analysis demonstrated that belonging to an AANHPI racial/ethnic group, excluding Japanese and Filipino, was associated with decreased risk of overall mortality. Significant differences were identified in the overall median survival for patients with pancreatic cancer between AANHPI subpopulations. Disparities in socioeconomic factors may have played a role in overall survival. This study highlights the need to include disaggregated data in future studies to subdue disparities in cancer care for patients.

Effect of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma: a real-world retrospective study

BackgroundGenitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC).MethodsWe performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed.ResultsForty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84–21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08–0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism.ConclusionsAmong patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

Evaluation of Efficacy and Prognosis Analysis of Stage III-IV SMARCA4-deficient Non-small Cell Lung Cancer Treated by PD-1 Immune Checkpoint Inhibitors plus Chemotherapy and Chemotherapy

The SMARCA4 mutation has been shown to account for at least 10% of non-small cell lung cancer (NSCLC). In the present, conventional radiotherapy and targeted therapy are difficult to improve outcomes due to the highly aggressive and refractory nature of SMARCA4-deficient NSCLC (SMARCA4-DNSCLC) and the absence of sensitive site mutations for targeted drug therapy, and chemotherapy combined with or without immunotherapy is the main treatment. Effective SMARCA4-DNSCLC therapeutic options, however, are still debatable. Our study aimed to investigate the efficacy and prognosis of programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy in patients with stage III-IV SMARCA4-DNSCLC. 46 patients with stage III-IV SMARCA4-DNSCLC were divided into two groups based on their treatment regimen: the chemotherapy group and the PD-1 ICIs plus chemotherapy group, and their clinical data were retrospectively analyzed. Efficacy assessment and survival analysis were performed in both groups, and the influencing factors for prognosis were explored for patients with SMARCA4-DNSCLC. Male smokers are more likely to develop SMARCA4-DNSCLC. There was no significant difference in the objective response rate (76.5% vs 69.0%, P=0.836) between chemotherapy and the PD-1 ICIs plus chemotherapy or the disease control rate (100.0% vs 89.7%, P=0.286). The one-year overall survival rate in the group with PD-1 ICIs plus chemotherapy was 62.7%, and that of the chemotherapy group was 46.0%. The difference in median progression-free survival (PFS) between the PD-1 ICIs plus chemotherapy group and the chemotherapy group was statistically significant (9.3 mon vs 6.1 mon, P=0.048). The results of Cox regression analysis showed that treatment regimen and smoking history were independent influencing factors of PFS in patients with stage III-IV SMARCA4-DNSCLC, and family history was an individual influencing factor of overall survival in patients with stage III-IV SMARCA4-DNSCLC. Treatment regimen may be a prognostic factor for patients with SMARCA4-DNSCLC, and patients with PD-1 ICIs plus chemotherapy may have a better prognosis.

Laparoscopic minor liver resection for hepatocellular carcinoma.

Previous studies have suggested that laparoscopic liver resection for hepatocellular carcinoma is associated with lower postoperative complications compared with open liver resection. We conducted a retrospective analysis of 109 hepatocellular carcinoma patients who underwent minor liver resection at a Japanese tertiary care hospital from November 2010 to December 2022. The laparoscopic liver resection group experienced significantly lower median intraoperative blood loss compared with the open liver resection group (P=0.0001). Furthermore, the laparoscopic liver resection group had a significantly shorter median hospital stay compared with the open liver resection group (P=0.0002). However, there was no significant difference in median postoperative survival between the laparoscopic liver resection group and the open liver resection group (P=0.717). Laparoscopic minor liver resection for hepatocellular carcinoma resulted in reduced blood loss and hospital stay without compromising long-term survival outcomes.

Clinicopathological Features and Prognosis of Resected Pancreatic Ductal Adenocarcinoma Patients with Claudin-18 Overexpression.

Claudin-18.2 (CLDN18.2) is specifically expressed in pancreatic precancerous lesions and pancreatic ductal adenocarcinoma (PDAC). We assessed the clinical characteristics of patients with CLDN18.2-overexpressing pancreatic cancer to identify patients who might benefit from CLDN18-targeted treatment. A total of 130 patients with surgically resected PDAC were investigated for the immunohistochemical expression of claudin-18 (CLDN18). The CLDN18 staining intensities (0-3+) and relative proportion of positive tumor cells were analyzed by two independent raters. Tumors positive for CLDN18 expression were defined as ≥80% of tumor cells with 2+ or 3+ staining intensity in a CLDN18 immunohistochemical assay. Positive CLDN18 expression was present in 41/130 (31.5%) surgically resected PDACs and the relative proportion of positive tumor cells and the staining intensity were directly correlated (p < 0.001). Positive CLDN18 expression was significantly associated with well-differentiated tumors (p < 0.001) and less regional node involvement (p = 0.045). The positive CLDN18-expressing group showed no statistical difference in median overall survival (17.4 months vs. 20.6 months, p = 0.770) compared to the negative CLDN18-expressing group. Distant nodal metastasis was more frequent in the positive CLDN18-expressing group (p = 0.011). CLDN18 is frequently expressed in PDAC, and high CLDN18-expressing PDACs showed some different clinicopathologic characteristics. High CLDN18 expression was not associated with prognosis in patients with surgically resected PDAC.

Repetitive nerve stimulation on survival in amyotrophic lateral sclerosis.

No previous studies investigated the association between decrement of low-frequency repetitive nerve stimulation (LF-RNS) and amyotrophic lateral sclerosis (ALS) survival. We aim to study the relationship between decrement and survival in ALS. Sporadic ALS patients diagnosed at the Department of Neurology, the First Medical Center, Chinese PLA General Hospital from January 2018 to December 2019 were enrolled in this study. Experienced neurologists followed up the participants regularly every 6 months until January 2022. A decremental response of 10% or greater at least in one muscle was considered positive. According to the decrement, the participants were divided into LF-RNS (+) and LF-RNS (-) groups. One hundred and eighty-one sporadic ALS patients were recruited in our study, including 100 males and 81 females. Among them, 10 cases (5.5%) were lost to follow-up, 99 cases (54.7%) died, and 72 patients (39.8%) were still alive at the last follow-up. The median survival time of all ALS patients in this study was 42.0 months. There was no significant difference of median survival in LF-RNS(+) group and LF-RNS(-) group (p = 0.159, Kaplan-Meier method). In multivariate Cox regression analysis, age of onset, diagnostic delay, and ALS Functional Rating Scale-Revised (ALSFRS-R) score were associated with ALS survival, but the decrement was not correlated with ALS survival (p = 0.238). The decrement in accessory and ulnar nerves was not associated with the survival of ALS. The decrement of LF-RNS could not be an electrophysiological marker to predict ALS survival.

Long-Term Survival among Octogenarians Undergoing Aortic Valve Replacement with or without Simultaneous Coronary Artery Bypass Grafting: A 22-Year Tertiary Single-Center Experience.

The impact of concomitant coronary artery bypass grafting (CABG) on aortic valve replacement (AVR) in octogenarians is still debated. We analyzed the characteristics and long-term survival of octogenarians undergoing isolated AVR and AVR + CABG. All octogenarians who consecutively underwent AVR with or without concomitant CABG at our tertiary cardiac center between 2000 and 2022 were included. Patients with redo, emergent, or any other concomitant procedures were excluded. The primary endpoints were 30-day and long-term survival. The secondary endpoints were early postoperative outcomes and determinants of long-term survival. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of 30-day mortality, and Cox regression analysis was performed for predictors of adverse long-term survival. A total of 1011 patients who underwent AVR (83.0 [81.0-85.0] years, 42.0% males) and 1055 with AVR + CABG (83.0 [81.2-85.4] years, 66.1% males) were included in our study. Survival at 30 days and at 1, 3, and 5 years in the AVR group was 97.9%, 91.5%, 80.5%, and 66.2%, respectively, while in the AVR + CABG group it was 96.2%, 89.6%, 77.7%, and 64.7%, respectively. There was no significant difference in median postoperative survival between the AVR and AVR + CABG groups (7.1 years [IQR: 6.7-7.5] vs. 6.6 years [IQR: 6.3-7.2], respectively, p = 0.21). Significant predictors of adverse long-term survival in the AVR group included age (hazard ratio (HR): 1.09; 95% CI: 1.06-1.12, p < 0.001), previous MI (HR: 2.08; 95% CI: 1.32-3.28, p = 0.002), and chronic kidney disease (HR 2.07; 95% CI: 1.33-3.23, p = 0.001), while in the AVR + CABG group they included age (HR: 1.06; 95% CI: 1.04-1.10, p < 0.001) and diabetes mellitus (HR: 1.48; 95% CI: 1.15-1.89, p = 0.002). Concomitant CABG was not an independent risk factor for adverse long-term survival (HR: 0.89; 95% CI: 0.77-1.02, p = 0.09). The long-term survival of octogenarians who underwent AVR or AVR + CABG was similar and was not affected by adding concomitant CABG. However, octogenarians who underwent concomitant CABG with AVR had significantly higher in-hospital mortality. Each decision should be discussed within the heart team.

Intratumoral heterogeneity as a predictive biomarker in immunotherapy for advanced esophageal cancer.

e16059 Background: Previous studies have shown that the acquired resistance to anti-cancer therapy is largely due to intratumoral heterogeneity (ITH), thus leading to unfavourable prognosis. As known, there is no comprehensive research using ITH as a biomarker to predict the efficacy of immunotherapy in advanced esophageal cancer (ESCA) patients. Methods: Bioconductor R package Maftools was used to analyze somatic variants of advanced ESCA from MSK-IMPACT-1611 study cohort (PMID: 30643254) with data from 39 patients. We then used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH score and analyzed the difference in the genetic profile between the ITH score high (ITH-H) and ITH score low (ITH-L) groups, the association with tumor mutational burden (TMB), and the effect of ITH on the prognosis of immunotherapy. Results: There were significant differences in gene mutation spectrum between ITH-H and ITH-L groups. The genes with the highest mutation frequency in ITH-H group were TP53 (93.75%), CDKN2A (37.5%), PREX2 (31.25%), PTPRD (25%), ALK (18.75%), ERBB4 (18.75%), and KMT2D (18.75%), while the genes with the highest mutation frequency in ITH-L group were TP53 (69.57%), CDKN2A (21.74%), PIK3CA (21.74%), APC (17.39%), ARID1A (17.39%), LATS1 (17.39%), and RNF43 (17.39%).There was significant difference in median overall survival (mOS) between ITH-L and ITH-H groups (not reach versus 5 months, hazard ratio (HR) = 3.96, 95%CI 1.02−15.39, P = 0.034). There was no significant difference in median TMB levels between ITH-L and ITH-H groups (7 Muts/Mb versus 8 Muts/Mb, P = 0.09). The TMB high (TMB-H) patients had no significantly better mOS than the TMB low (TMB-L) group (HR = 0.27, 95%CI 0.06−1.26, P = 0.072). A pooled analysis of ITH and TMB show that mOS in the ITH-L+ TMB-H group was significantly better than that in the ITH-L+TMB-L, ITH-H+TMB-H, and ITH-H+TMB-L group (HR = 2.03, 95%CI 0.06−7.69, P = 0.002). Conclusions: The results suggest ITH is a predictor of ESCA immunotherapy efficacy independent of TMB.

Effects of Traditional Chinese Medicine on the survival of patients with stage I gastric cancer and high-risk factors: a real-world retrospective study.

To investigate the benefits of Traditional Chinese Medicine (TCM) therapy for improving the survival of patients with stage I gastric cancer (GC) and high-risk factors in a real-world setting. The clinical data of patients who were diagnosed with stage I GC from March 1, 2012 to October 31, 2020 were collected. Prognostic analysis was performed to explore the high-risk factors that affected the survival of the patients. A Cox multivariate regression model was used to compare the hazard ratios for the mortality risk of patients, especially those with high-risk factors. Kaplan-Meier survival curve and log-rank test were utilized to assess the survival time. Prognostic analysis demonstrated that female sex, tumor invasion into blood vessels, and Ib stage were independent risk factors. The 1-, 3-, and 5-year survival rates of the TCM group those of the non-TCM group were 100.0% 91.0%, 97.6% 64.5%, and 81.4% 55.5%, respectively. A significant difference in median overall survival (mOS) was found between the two groups (χ = 7.670, = 0.006). Subgroup analysis showed that the mOS of female patients and stage Ib patients in the TCM group were longer than those in the non-TCM group ( ≤ 0.001 and 0.001, respectively). TCM treatment can improve the survival of patients with stage I GC and high-risk factors.

Influence of levothyroxine concomitant treatment on treatment responses and outcomes in patients with metastatic colorectal adenocarcinoma.

e15593 Background: Hypothyroidism is the most common thyroid disorder and levothyroxine is the mainstay treatment. Levothyroxine is mainly used to restore the euthyroid clinical and biochemical status in the gland. Recent literature has correlated chronic hormonal treatment with adverse effects on bone and heart function, as well as correlated with an increased risk of tumor onset. Data available in the literature are controversial, therefore the aim of our study was to evaluate the correlation between chronic levothyroxine intake and outcomes and response to first line treatments in patients affected by metastatic colorectal cancer. Methods: We retrospectively collected the data from 139 patients with metastatic colorectal adenocarcinoma, belonging to the Medical Oncology Department of the University Hospital of Cagliari from 2016 to 2019. All patients enrolled in the study had received metastatic first-line treatment with doublet or triplet chemotherapy associated with anti-VEGF or anti-EGR monoclonal antibody. Patients with ECOG PS ≤1 with no more than two relevant comorbidities were included in the study. The primary objective of the study was median overall survival (mOS) and secondary objectives were: median progression free progression (PFS), median overall survival (mOS) differences between RAS wild type and mutant tumour. BRAF mutant tumors were excluded from the evaluation. Results: Median age was 65 years (±10), 51% were male and 49% were female. 63% patients had an ECOG-PS 0, while 37% had an ECOG-PS 1. 67% developed from the left colon; 33% from the right colon and the transverse colon. All patients had synchronous metastases. 18% patients took levothyroxine and 82% patients did not take it. Among the patients receiving levothyroxine therapy, 64% had a RAS wild type and 36% a RAS mutated. Levothyroxine treated patients showed a significantly lower median OS than not treated patients (15 months versus not reached, p = 0,0001). Levothyroxine treated patients also showed a significantly lower median PFS than non treated patients (6 versus 8 months, p = 0,035). Within levothyroxine treated pts, no statistically significant differences were found in mOS and mPFS between RAS wt and RAS mut (mOS 15 versus 14 months, respectively, p = 0.9; mPFS 8 versus 7 months, respectively, p = 0,7). Conclusions: The results show a possible correlation between levothyroxine therapy and outcomes in mCRC. This would deserve further study to understand further biological-molecular aspects, to date partially explained by preclinical studies, in order to clarify some of the possible underlying mechanisms.

The Effect of COVID-19 Restrictions on General and HIV Positive Inpatient Admissions and Treatment Outcomes: An Uncontrolled Before-and-after Study at a Ugandan Tertiary Hospital.

Measures to contain the Corona Virus Disease 2019 (COVID-19) pandemic curtailed access to prevention and treatment services for endemic infectious diseases like HIV. We used an uncontrolled before-and-after study design to compare general and HIV positive (HIV+) inpatient outcomes at a tertiary hospital in Uganda, using electronic records of medical inpatients. Data was downloaded, cleaned in Microsoft Excel, and exported to STATA for analysis. We determined the difference in number of admissions and median length of hospital stay using Mann-Whitney U test; and difference in median survival and incidence rates of mortality using Kaplan - Meier statistics, between the pre- and peri-COVID-19 groups. Of 7506 patients admitted to Kiruddu NRH, 50.8% (3812) were female and 18.7% (1,401) were aged 31-40 years, and 18.8% (1,411) were HIV+. Overall, 24.6% (1849) died. Total admissions were lower (2192 vs. 5314 patients), overall mortality rate higher (41.8% vs. 17.6%, p < 0.01), median length of hospital stay longer (6 vs. 4 days, p < 0.01) and median survival shorter (11 vs. 20 days, Chi-square = 252.05, p < 0.01) in the peri- than in pre-COVID-19 period. The adjusted hazard ratio (aHR) of death was 2.08 (95% CI: 1.85-2.23, p < 0.01) in the peri- compared to the pre-COVID-19 period. These differences were more pronounced in HIV + patients. Compared to pre-COVID-19, the peri-COVID-19 period registered lower inpatient admissions but poorer treatment outcomes for general and HIV + inpatients. Emerging epidemic responses should minimize disruption to inpatient care, especially for HIV + individuals.

Treatment paradigm and prognostic factor analyses of rectal squamous cell carcinoma.

Rectal squamous cell carcinoma (rSCC) is a rare pathological subtype of rectal cancer. There is no consensus on the treatment paradigm for patients with rSCC. This study aimed to provide a paradigm for clinical treatment and develop a prognostic nomogram. Patients diagnosed with rSCC between 2010 and 2019 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. According to the TNM staging system, Kaplan-Meier (K-M) survival analysis was used to identify the survival benefits of different treatments in patients with rSCC. The Cox regression method was used to identify independent prognostic risk factors. Nomograms were evaluated by Harrell's concordance index (C-index), calibration curves, decision curve analysis (DCA) and K-M curves. Data for 463 patients with rSCC were extracted from the SEER database. Survival analysis showed that there was no significant difference in median cancer-specific survival (CSS) among patients with TNM stage 1 rSCC treated with radiotherapy (RT), chemoradiotherapy (CRT) or surgery (P = 0.285). In TNM stage 2 patients, there was a significant difference in median CSS among those treated with surgery (49.5 months), RT (24 months), and CRT (63 months) (P = 0.003). In TNM stage 3 patients, there was a significant difference in median CSS among those treated with CRT (58 months), CRT plus surgery (56 months) and no treatment (9.5 months) (P < 0.001). In TNM stage 4 patients, there was no significant difference in median CSS among those treated with CRT, chemotherapy (CT), CRT plus surgery and no treatment (P = 0.122). Cox regression analysis showed that age, marital status, T stage, N stage, M stage, PNI, tumor size, RT, CT, and surgery were independent risk factors for CSS. The 1-, 3-, and 5-year C-indexes were 0.877, 0.781, and 0.767, respectively. The calibration curve showed that the model had excellent calibration. The DCA curve showed that the model had excellent clinical application value. RT or surgery is recommended for patients with stage 1 rSCC, and CRT is recommended for patients with stage 2, and stage 3 rSCC. Age, marital status, T stage, N stage, M stage, PNI, tumor size, RT, CT, and surgery are independent risk factors for CSS in patients with rSCC. The model based on the above independent risk factors has excellent prediction efficiency.

Docetaxel plus S-1 versus docetaxel plus capecitabine as first-line treatment for advanced breast cancer patients: a prospective randomized phase II study

BackgroundThis study was conducted to evaluate the efficacy and safety of docetaxel/S-1 (TS) compared with docetaxel/capecitabine (TX) as a first-line treatment for advanced breast cancer. MethodsPatients with advanced metastatic breast cancer were randomly divided into the TS group (n = 54) and the TX group (n = 57) for first-line chemotherapy from August 2015 to April 2019 (ClinicalTrials.org registration no. NCT02947061). Following the completion of combination therapy, patients without progression received S-1 or capecitabine maintenance treatment. The primary end point was progression-free survival (PFS). ResultsAmong 111 enrolled patients, the median PFS did not differ significantly between the TS group and the TX group (TS vs. TX, 9.0 vs. 7.4 months, P = 0.365, 95% confidence interval [CI]: 0.50–1.11, hazard ratio [HR]: 0.75). There was also no statistically significant difference in median overall survival (OS) between the two groups (TS vs. TX, 40.2 vs. 41.3 months, P = 0.976). In addition, visceral metastasis and metastasis sites, such as the liver or lung, did not lead to a significant effect on PFS and OS. The two regimens showed no significant difference in adverse events, except hand-foot syndrome, which predominated in the TX group (38.6% vs. 7.4%, P = 0.001), and diarrhea (24.1% vs. 3.6%, P = 0.003) and elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels (14.8% vs. 3.5%, P = 0.049), which were more frequent in the TS group. ConclusionsThe TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast cancer. The TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen, representing an effective alternative option to the TX regimen. Further studies are warranted to define the efficacy and safety of this strategy in real-world settings.