Difference In Median Survival Research Articles

The pluripotency factor NANOG contributes to mesenchymal plasticity and is predictive for outcome in esophageal adenocarcinoma

BackgroundDespite the advent of neoadjuvant chemoradiotherapy (CRT), overall survival rates of esophageal adenocarcinoma (EAC) remain low. A readily induced mesenchymal transition of EAC cells contributes to resistance to CRT.MethodsIn this study, we aimed to chart the heterogeneity in cell state transition after CRT and to identify its underpinnings. A panel of 12 esophageal cultures were treated with CRT and ranked by their relative epithelial-mesenchymal plasticity. RNA-sequencing was performed on 100 pre-treatment biopsies. After RNA-sequencing, Ridge regression analysis was applied to correlate gene expression to ranked plasticity, and models were developed to predict mesenchymal transitions in patients. Plasticity score predictions of the three highest significant predictive models were projected on the pre-treatment biopsies and related to clinical outcome data. Motif enrichment analysis of the genes associated with all three models was performed.ResultsThis study reveals NANOG as the key associated transcription factor predicting mesenchymal plasticity in EAC. Expression of NANOG in pre-treatment biopsies is highly associated with poor response to neoadjuvant chemoradiation, the occurrence of recurrences, and median overall survival difference in EAC patients (>48 months). Perturbation of NANOG reduces plasticity and resensitizes cell lines, organoid cultures, and patient-derived in vivo grafts.ConclusionsIn conclusion, NANOG is a key transcription factor in mesenchymal plasticity in EAC and a promising predictive marker for outcome.

Time from diagnosis to treatment has no impact on survival in newly diagnosed acute myeloid leukemia treated with venetoclax-based regimens.

In newly diagnosed acute myeloid leukemia, immediate initiation of treatment is standard of care. However, deferral of antileukemic therapy may be indicated to assess comorbidities or pre-therapeutic risk factors. We explored the impact of time from diagnosis to treatment on outcomes in newly diagnosed acute myeloid leukemia undergoing venetoclax-based therapy in two distinct cohorts. By querying the Study Alliance Leukemia database and the global health network TriNetX, we identified 138 and 717 patients respectively with an average age of 76 and 72 years who received venetoclax-based firstline therapy. When comparing patients who started treatment earlier or later than 10 days after initial diagnosis, no significant difference in median overall survival was observed - neither in the SAL cohort (7.7 vs. 9.6 months, p=.42) nor in the TriNetX cohort (7.5 vs. 7.2 months, p=.41). Similarly, severe infections, bleeding, and thromboembolic events were equally observed between early and later treatments, both in the overall patient groups and specific subgroups (age ≥75 years or leukocytes ≥20x109/L). This retrospective analysis indicates that delaying the start of venetoclax-based therapy in newly diagnosed acute myeloid leukemia might be a safe option for selected patients, provided that close clinical monitoring is performed.

Escalating Surgical Treatment for Left Ventricular Assist Device Infection and Expected Mortality: Clinical Risk Prediction Score.

Left ventricular assist devices (LVAD) improve survival for patients with cardiac failure, but LVAD specific infections (VSI) remain a challenge with poorly understood predictive risk factors. Furthermore, the indications and utility of escalating medical treatment to surgical debridement and potential flap reconstruction are not well-characterized. A retrospective review of consecutive patients undergoing primary LVAD implantation at a tertiary academic center was performed. The primary outcomes measures were 90-day and overall mortality after VSI. Cox proportional hazards regression was used to generate a risk-prediction score for mortality. Of the 760 patients undergoing primary LVAD implantation, 255 (34%) developed VSI; of these 91 (36%) were managed medically, 134 (52%) with surgical debridement, and 30 (12%) with surgical debridement and flap reconstruction. One-year survival after infection was 85% with median survival of 2.40 years. Factors independently associated with increased mortality were diabetes (hazard ratio (HR) 1.44, p=0.04), methicillin-resistant Staphylococcus aureus infection (HR 1.64, p=0.03), deep space (pump pocket/outflow cannula) involvement (HR 2.26, p<0.001) and extra-corporeal membrane oxygenation after LVAD (HR 2.52, p<0.01. Factors independently associated with decreased mortality were flap reconstruction (HR 0.49, p=0.02) and methicillin-sensitive Staphylococcus aureus infection (HR 0.63, p=0.03). A clinical risk prediction score was developed using these factors and showed significant differences in median survival, which was 5.67 years for low-risk (score 0-1), 3.62 years for intermediate-risk (score 2), and 1.48 years for high-risk (score >3) (p<0.001) patients. We developed a clinical risk prediction score to stratify VSI patients. In selected cases, escalating surgical treatment was associated with increased survival. Future work is needed to determine if early surgical debridement and flap reconstruction can alter outcomes in select cases of VSI.

The Real-Life Impact of Primary Tumor Resection of Synchronous Metastatic Colorectal Cancer-From a Clinical Oncologic Point of View.

The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for and against it. We aimed to define its effect and find its best place in our therapeutic methodology. We performed retrospective data analysis to investigate the clinical course of 449 smCRC patients, considering treatment modalities and the location of the primary tumor and comparing the clinical results of the patients with or without PTR between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs. A total of 63.5% of the 449 smCRC patients had PTR. Comparing their data to those whose primary tumor remained intact (IPT), we observed significant differences in median progression-free survival with first-line chemotherapy (mPFS1) (301 vs. 259 days; p < 0.0001; 1 y PFS 39.2% vs. 26.6%; OR 0.56 (95% CI 0.36-0.87)) and median overall survival (mOS) (760 vs. 495 days; p < 0.0001; 2 y OS 52.4 vs. 26.9%; OR 0.33 (95% CI 0.33-0.53)), respectively. However, in the PTR group, the average ECOG performance status was significantly better (0.98 vs. 1.1; p = 0.0456), and the use of molecularly targeted agents (MTA) (45.3 vs. 28.7%; p = 0.0005) and rate of metastasis ablation (MA) (21.8 vs. 1.2%; p < 0.0001) were also higher, which might explain the difference partially. Excluding the patients receiving MTA and MA from the comparison, the effect of PTR remained evident, as the mOS differences in the reduced PTR subgroup compared to the reduced IPT subgroup were still strongly significant (675 vs. 459 days; p = 0.0009; 2 y OS 45.9 vs. 24.1%; OR 0.37 (95% CI 0.18-0.79). Further subgroup analysis revealed that the site of the primary tumor also had a major impact on the outcome considering only the IPT patients; shorter mOS was observed in the extrapelvic IPT subgroup in contrast with the intrapelvic IPT group (422 vs. 584 days; p = 0.0026; 2 y OS 18.2 vs. 35.9%; OR 0.39 (95% CI 0.18-0.89)). Finally, as a remarkable finding, it should be emphasized that there were no differences in OS between the smCRC PTR subgroup and metachronous mCRC patients (mOS 760 vs. 710 days, p = 0.7504, 2 y OS OR 0.85 (95% CI 0.58-1.26)). The role of PTR in smCRC is still not professionally justified. Our survey found that most patients had benefited from PTR. Nevertheless, further prospective trials are needed to clarify the optimal treatment sequence of smCRC patients and understand this cancer disease's inherent biology.

Immediate Versus Deferred Systemic Therapy in Patients With Mesothelioma

BackgroundThe 2018 ASCO pleural mesothelioma (PM) treatment guideline states that “a trial of expectant observation may be offered” in patients with asymptomatic inoperable epithelioid mesothelioma with low disease burden. The aim of our analysis was to evaluate clinical characteristics and outcomes in PM-patients managed with initial observation and deferred treatment initiation. MethodsWe retrospectively collected clinicodemograhic and outcome data of patients with inoperable PM. Patients were assigned to 2 treatment decision groups: decision to start immediate systemic treatment (Immediate Treatment Group) versus observation and deferring treatment (Deferred Treatment group). ResultsOf 222 patients with advanced PM, systemic treatment was started immediately in the majority of patients (189, 85%; immediate group); treatment was deferred in 33 (15%) patients (deferred group); systemic therapy was chemotherapy-based in 91% and 79% respectively. Patients in the deferred group were older (70 vs 67 years, p = .05), less likely to have stage IV disease (28% vs. 51%, p = .08) and more often had epithelioid histology (90% vs. 70%, p = .03). Nineteen patients (58%) in the deferred group eventually received treatment.With a median follow-up time of 10.9 months median overall survival (OS) in the entire cohort was 12.4 months and was significantly longer in the deferred group (20.6 months vs. 11.5 months, p = .02). No difference in median progression-free survival (PFS) in first-line treatment between groups was seen (5.4 and 5.3 months). ConclusionThis real-world analysis suggests that deferral of systemic therapy and close observation may not impact OS or physician-assessed PFS in selected PM-patients.

Impact of race and social determinants of health on outcomes in patients with aggressive B-cell NHL treated with CAR-T therapy

AbstractChimeric antigen receptor (CAR) T-cell (CAR-T) immunotherapy is an effective therapy for relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). However, data are limited on the impact of the convergence of race and social determinants of health on outcomes for patients treated with CAR-T therapy. We examined the impact of interactions between race and insurance type on health care use and outcomes in patients treated with CAR-T therapy for aggressive B-NHL. Adult patients with r/r B-NHL treated with CD19 CAR-Ts were identified between 2015 and 2021 across 13 US academic centers. Insurance type, demographic, and clinical data were collected and analyzed. In total, 466 adult patients were included in our analysis. Median follow-up after CAR-T therapy was 12.7 months. Median progression-free survival (mPFS) was longer for Caucasians (11.5 months) than for African Americans (3.5 months; hazard ratio [HR], 1.56 [1.03-2.4]; P = .04) or Asians (2.7 months; HR, 1.7 [1.02-2.67]; P = .04). Differences in median overall survival (mOS) were not significant. For Medicare (n = 206) vs Medicaid (n = 33) vs private insurance (n = 219) vs self-pay (n = 7): mPFS was 15.9 vs 4.2 vs 6.0 vs 0.9 months (P < .001), respectively; and mOS was 31.2 vs 12.8 vs 21.5 vs 3.2 months (P < .001), respectively. Our multicenter retrospective analysis showed that race and insurance status can affect outcomes for patients treated with CAR-T therapy.

Therapy-related chronic myelomonocytic leukemia does not have the high-risk features of a therapy-related neoplasm

AbstractTherapy-related myeloid neoplasms (t-MNs) arise after exposure to cytotoxic therapies and are associated with high-risk genetic features and poor outcomes. We analyzed a cohort of patients with therapy-related chronic myelomonocytic leukemia (tCMML; n = 71) and compared its features to that of de novo CMML (dnCMML; n = 461). Median time from cytotoxic therapy to tCMML diagnosis was 6.5 years. Compared with dnCMML, chromosome-7 abnormalities (4% vs 13%; P = .005) but not complex karyotype (3% vs 7%; P = .15), were more frequent in tCMML. tCMML was characterized by higher TP53 mutation frequency (4% vs 12%; P = .04) and lower NRAS (6% vs 22%, P = .007) and CBL (4% vs 12%, P = .04) mutation frequency. Prior therapy with antimetabolites (odd ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.42; P = .01) and mitotic inhibitors (OR, 1.24; 95% CI, 1.06-1.44; P = .009) was associated with NF1 and SETBP1 mutations whereas prior mitotic inhibitor therapy was associated with lower TET2 mutation frequency (OR, 0.71; 95% CI, 0.55-0.92; P = .01). Although no differences in median overall survival (OS) were observed among tCMML and dnCMML (34.7 months vs 35.9 months, P = .26), multivariate analysis for OS revealed that prior chemotherapy was associated with increased risk of death (hazard ratio, 1.76; 95% CI, 1.07-2.89; P = .026). Compared with a cohort of therapy-related myelodysplastic syndrome, tCMML had lower TP53 mutation frequency (12% vs 44.4%, P < .001) and less unfavorable outcomes. In summary, tCMML does not exhibit the high-risk features and poor outcomes of t-MNs.

Assessing the clinical benefit of systemic anti-cancer treatments in the Netherlands: The impact of different thresholds for effectiveness

BackgroundIn the Netherlands, the clinical benefit of systemic anti-cancer treatments (SACTs) is assessed by the Committee for the Evaluation of Oncological Agents (cieBOM). For non-curative SACTs, the assessment is based on the hazard ratio (HR) for progression-free survival and/or overall survival (OS), and the difference in median survival. We evaluated the impact of different thresholds for effectiveness by reassessing the clinical benefit of SACTs. MethodsWe reassessed SACTs that were initially assessed by cieBOM between 2015 and 2017. Four scenarios were formulated: replacing an “OR” approach (initial assessment) by an “AND” approach (used in all scenarios), changing the HR threshold from < 0.70 (initial assessment) to < 0.60, changing the threshold for the difference in median survival from > 12 weeks (initial assessment) to > 16 weeks, and including thresholds for OS rates. The outcomes of these scenarios were compared to the outcomes of the initial assessment. ResultsReassessments were conducted for 41 treatments. Replacing the “OR” approach by an “AND” approach substantially decreased the number of positive assessments (from 33 to 22), predominantly affecting immunotherapies. This number further decreased (to 21 and 19, respectively) in case more restrictive thresholds for the HR and difference in median survival were used. Including thresholds for OS rates slightly mitigated the impact of applying an “AND” approach. ConclusionsThe scenario-specific thresholds had a substantial impact; the number of negative assessments more than doubled. Since this was not limited to treatments with marginal survival benefits, understanding the potential challenges that may arise from applying more restrictive thresholds is essential.

A292 IMPACT OF SIROLIMUS PROTEINURIA FOLLOWING LIVER TRANSPLANTATION

Abstract Background Sirolimus (Sr) is a potent immunosuppressant used in liver transplant recipients to prevent rejection in settings of calcineurin inhibitor toxicity and in transplanted hepatocellular carcinoma (HCC) patients. Sr can cause proteinuria, which can lead to poor renal function and survival. The significance of proteinuria is poorly understood, with a lack of studies assessing its risk factors and their impact on clinical outcomes. Aims We evaluated the incidence of proteinuria and its impact on clinical outcomes among liver transplant (LT) recipients who were Sr users compared with non-sirolimus (nonSr) users. Methods We analyzed patients with their first LT between 2001 and 2020. Data were gathered from Organ Transplant Tracking records and chart reviews. Sr users received Sr for at least 6 consecutive months in the first year post-LT. We studied demographics, pre-LT comorbidities, and immunosuppression use. We evaluated the development of proteinuria, renal dysfunction, and new comorbidities including features of metabolic syndrome and cardiovascular disease. Data on post-LT infections, graft rejection, and patient survival were collected. Results We analyzed 359 Sr and 762 non-Sr users (73.5% vs. 65% male). The average ages of Sr and non-Sr users were 54.9±9 and 51.7±11.6 years, respectively (pampersand:003C0.001). Of Sr users, 40.4% had HCC (pampersand:003C0.001). Among non-Sr users, 95% were on tacrolimus and 67.8% were on mycophenolate. Higher frequency of pre-LT hypertension (HTN) was observed in Sr users (27.2% vs. 18.2%; pampersand:003C0.001). There were no differences in pre-LT chronic kidney disease (CKD), cardiovascular disease (CVD), dyslipidemia (DLD), diabetes mellitus (DM) prevalence, creatinine levels, or proteinuria. Sr users had a higher incidence of proteinuria (13.1% vs. 7.9%, p=0.006). Protein-creatinine ratios and albumin-creatinine ratios 12 months post-LT were not significantly different in Sr and non-Sr users ([40.1±105.6 vs. 57.5±169.9 mg/g, p=0.39], and [56.2±101.4 vs. 54.6±166.8 mg/g, p=0.268], respectively). Pre-LT creatinine (OR1.5; pampersand:003C 0.001) and DM (OR2.7; pampersand:003C 0.001) were associated with an increased risk of proteinuria. Sr users had higher (pampersand:003C0.001) incidence of post-LT CVD (24% vs. 14.8%), DM (20.4% vs. 12.6%), HTN (41.5% vs. 30.3%), and DLD (41.3% vs. 20.3%). There was no difference in post-LT CKD between Sr vs non-Sr (41% vs. 47%; p =0.119). Sr users had a lower frequency of post-LT infection (43.1% vs. 53%, p=0.007). Higher incidence of graft rejection was seen in Sr users (43.5% vs 27.8%, pampersand:003C0.001). There was no difference in median graft (15.2 ± 0.40 vs. 14.4±0.30 years; p = 0.681) or patient survival (12.5±0.44 vs. 12.5±0.33 years; p = 0.536). Conclusions Although Sr users were less likely to develop CKD post-LT, they had significantly higher rates of proteinuria, CVD, HTN, and DLD. However, no significant difference was observed in graft or patient survival rates. Funding Agencies None

Machine learning based on blood test biomarkers predicts fast progression in advanced NSCLC patients treated with immunotherapy

ObjectiveFast progression (FP) represents a desperate situation for advanced non-small cell lung cancer (NSCLC) patients undergoing immune checkpoint inhibitor therapy. We aimed to develop a predictive framework based on machine learning (ML) methods to identify FP in advanced NSCLC patients using blood test biomarkers.Methods and analysisWe extracted data of 1546 atezolizumab-treated patients from four multicentre clinical trials. In this study, patients from the OAK trial were taken for model training, whereas patients from the other trials were used for independent validations. The FP prediction model was developed using 21 pretreatment blood test variables in seven ML approaches. Prediction performance was evaluated by the receiver operating characteristic (ROC) curve.ResultsThe prevalence of FP was 7.6% (118 of 1546) in all atezolizumab-treated patients. The most important variables for the prediction model were: C reactive protein, neutrophil count, lactate dehydrogenase and alanine transaminase. The Support Vector Machine (SVM) algorithm applied to these four blood test parameters demonstrated good performance: the area under the ROC curve obtained from the training cohort (OAK), validation cohort 1 (BIRCH) and cohort 2 (merged POPLAR and FIR) were 0.908, 0.666 and 0.776, respectively. In addition, the absolute difference in median survival between the SVM-predicted FP and non-FP groups was significant in both progression-free survival and overall survival (p&lt;0.001).ConclusionSVM trained using a 4-biomarker panel has good performance in predicting the occurrence of FP regardless of programmed cell death ligand 1 expression, hence providing evidence for decision-making in single-agent atezolizumab immunotherapy for patients with advanced NSCLC.

Surgical site infections after glioblastoma surgery: boon or bane?

BackgroundSurgical site infections (SSIs) are among the most common postoperative complications. Glioblastoma multiforme is the most frequent malignant brain tumor with a dismal prognosis despite combined treatment. The effect of SSIs on the course of glioblastoma patients has not been fully clarified since available data are limited and partially contradictory. The aim of this study is to investigate the impact of SSIs on the course of patients with glioblastoma.MethodsThe medical records of all patients undergoing surgery for glioblastoma between 2010 and 2020 in our institution were scanned and those with surgical site infections after glioblastoma resection were identified and compared to an age-matched control group. Overall survival and progression-free survival were the primary endpoints followed by the number of hospitalizations and the length of stay in hospital.ResultsOut of 305 patients undergoing surgery for glioblastoma, 38 patients with postoperative surgical site infection after resection were identified and 15 (5 men and 10 women aged between 9 and 72) were included in this study. 23 patients were excluded. The control group consisted of 30 age-matched patients without SSI (18 men and 12 women). There were no significant differences in median overall survival. Progression-free survival was higher in the SSI group. The number of hospitalizations and the length of stay were significantly higher in the SSI group.ConclusionOur data suggest that SSIs might reduce early recurrences without affecting overall survival. Furthermore, they might decrease health-related quality of life by doubling the total length of hospital stay.

Non-responders to neoadjuvant chemotherapy in pancreatic adenocarcinoma: Characteristics and outcomes.

662 Background: For patients with localized pancreatic adenocarcinoma, resection and systemic therapy remain the mainstays of curative-intent treatment. Neoadjuvant chemotherapy has been frequently employed with the goals of addressing systemic disease early and improving patient selection for surgery. Those who do not respond to neoadjuvant therapy present a challenge with a lack of randomized data to aid in decision making. Here we sought to define the characteristics and outcomes of those patients to guide clinical practice. Methods: This was a single-institution retrospective cohort study using a prospectively maintained database of those diagnosed with pancreatic adenocarcinoma. Patients included in the study were those who received neoadjuvant chemotherapy. Non-responders were defined as those with both no radiographic and no biochemical response at the first re-assessment after initiation of therapy. Results: A total of 176 patients were identified who were treated with neoadjuvant chemotherapy with curative intent. Of those, 42 (23.8%) patients had no evidence of either radiographic or biochemical response. Of those patients, 14 were upfront resectable (33.3%) and 20 were borderline resectable (47.6%). An additional 8 (19%) were locally advanced. Most patients received FOLFIRINOX as a first line chemotherapy agent (n = 25, 59.5%). A total of 12 (28.6%) patients underwent neoadjuvant radiation therapy. A total of 19 (45.2%) proceeded to surgery and two of those were found to be unresectable at exploration, resulting in 17 (40.5%) who ultimately received curative-intent resection. Exactly half (n = 21) of the patients had their chemotherapy switched (CS). Of those who had CS, 11 (52.4%) had evidence of local tumor progression on their initial restaging scan compared to just 3 (14.3%) of those who did not (p = 0.02). Additionally, patients who had CS had higher incidence of vascular involvement on their initial scan (90.5% vs 52.3%, p = 0.051). A total of 6 (28.6%) who underwent CS had subsequent biochemical response compared 4 (19.0%) of those who did not. Ultimately, 6 (28.6%) of those who had CS ultimately proceeded to surgery compared to 13 (61.9%) of those who did not (p = 0.062). Interestingly, there was no significant difference in median overall survival between those who had CS (18.6 months) and those who did not (19.9 months, p = 0.525). Conclusions: Non-responders to frontline neoadjuvant systemic therapy present a clinical challenge and have poor rates of curative-intent resection. Chemotherapy switch was employed mostly in cases with worse prognostic factors and thus infrequently lead to resection. Despite this, patients who underwent CS had similar overall survival to those who did not. These data suggest there may be a role for chemotherapy switch in those who do not respond to front line chemotherapy.

Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution

BackgroundEsthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, and poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine-learning algorithm on ENB transcriptomic profiles. MethodsThe authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine-learning pipeline on RNAseq data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB. ResultsNo differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (p>0.05). No difference in median overall survival was also appreciated (52.0±13.1 vs. 50.0±43.2 months, p=0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B-cells (13%) and CD4 memory resting T cells (12%). No gross differences on CD20, CD4, or CD8 cells/mm2 were apparent on gross histology (p>0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB but did suggest immunoprofile differences. ConclusionBasal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.

Postoperative results, learning curve, and outcomes of pancreatectomy with arterial resection: a single-center retrospective cohort study on 236 procedures

Background: Newer chemotherapy regimens are reviving the role of pancreatectomy with arterial resection (PAR) in locally advanced pancreatic cancer. However, concerns about the early outcomes and learning curve of PAR remain. This study aimed to define the postoperative results and learning curve of PAR and provide preliminary data on oncologic outcomes. Materials and methods: A single center’s experiences (1993–2023) were retrospectively analyzed to define the postoperative outcomes and learning curve of PAR. Oncologic results were also reported. Results: During the study period 236 patients underwent PAR. Eighty PAR (33.9%) were performed until 2012, and 156 were performed thereafter (66.1%). Pancreatic cancer was diagnosed histologically in 183 patients (77.5%). Induction therapy was delivered to 18 of these patients (31.0%) in the early experience and to 101 patients (80.8%) in the last decade (P&lt;0.0001). The superior mesenteric artery (PAR-SMA), celiac trunk/hepatic artery (PAR-CT/HA), superior mesenteric/portal vein, and inferior vena cava were resected in 95 (40.7%), 138 (59.2%), 189 (80.1%), and 9 (3.8%) patients, respectively. Total gastrectomy was performed in 35 (18.5%) patients. The thirty-day mortality rate was 7.2% and ninety-day mortality rate was 9.7%. The learning curve for mortality was 106 PAR (16.0% vs. 4.6%; odds ratio, OR=0.25 [0.10–0.67], P=0.0055). Comparison between the PAR-SMA and PAR-CT/HA groups showed no differences in severe postoperative complications (25.3% vs. 20.6%), 90-day mortality (12.6% vs. 7.8%), and median overall survival. Vascular invasion was confirmed in 123 patients (67.2%). The median number (interquartile range) of examined lymph nodes was 60.5 (41.3–83) and rate of R0 resection was 66.1% (121/183). Median overall survival for PAR was 20.9 (12.5–42.8) months, for PAR-SMA was 20.2 (14.4–44) months, and for PAR-CT/HA was 20.2 (11.4–42.7). Long-term prognosis improved by study decade (1993–2002: 12.0 [5.4–25.9] months, 2003–2012: 15.1 [9.8–23.4] months, and 2013–present: 26.2 [14.3-51.5] months; P&lt;0.0001). Conclusions: In recent times, PAR is associated with improved outcomes despite a steep learning curve. Pancreatic surgeons should be prepared to face the technical challenge posed by PAR.

Genetic Alterations and Risk Factors for Recurrence in Patients with Non-Small Cell Lung Cancer Who Underwent Complete Surgical Resection

A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458–4.993; p = 0.002), stage II (HR: 2.614; 95% CI: 1.29–5.295; p = 0.008) or III disease (HR: 9.537; 95% CI: 4.825–18.852; p &lt; 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405–4.803; p = 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type (p = 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached; p = 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary.

Antithymocyte Globulin in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia: Evaluating Outcomes According to Cytogenetic Risk

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an essential therapeutic approach for the management of acute myeloid leukemia (AML). Nevertheless, graft-versus-host disease (GVHD) remains a significant complication, significantly affecting the recipients' quality of life and overall survival. Antithymocyte globulin (ATG) has demonstrated promise in preventing GVHD during allo-HSCT. However, concerns persist regarding its potential impact on disease relapse. This retrospective single-center study aims to evaluate the prognostic implications of ATG based on cytogenetic risk stratification in AML patients undergoing transplantation from an HLA-matched sibling. A total of 124 AML patients who underwent allo-HSCT from an HLA-matched sibling in their first complete remission state between 2003 and 2022 were eligible for the study. Among them, fifty patients received rabbit ATG at a dose of 2.5mg/kg/day for days -2 to -1, while 74 patients did not receive ATG. All patients received cyclosporine and methotrexate in addition to their respective conditioning regimens (ATG or no ATG). The ATG group consisted of 38 patients classified as having a non-high cytogenetic risk, and 12 patients classified as having a high cytogenetic risk. Conversely, the non-ATG group included 68 patients with a non-high cytogenetic risk and 6 patients with a high cytogenetic risk. After a median follow-up of 48 months, there were no significant differences in median overall survival between the ATG and Non-ATG groups, regardless of cytogenetic risk status (non-high cytogenetic risk; 12.4 months vs. NA, p = 0.578; high cytogenetic risk; 13.2 months vs. 14.2 months, p = 0.729, Figure A-1,B-1). The ATG group in the non-high cytogenetic risk group demonstrated a significant decrease in the 1-year cumulative incidence (CI) of chronic GVHD compared to the non-ATG group (21.7% vs. 54.4%, p = 0.001, Figure A-2; and in those with moderate to severe cGVHD, it was 21.6% vs. 51.5%, p = 0.003, respectively). Additionally, the 1-year Chronic GVHD-free and relapse-free survival (cGRFS) was higher in the ATG group of the non-high cytogenetic risk group (45.8vs. 26.5%; p = 0.048, Figure A-3). Moreover, there were no significant differences in 1-year CI of relapse and 1-year non-relapse mortality (NRM) within the non-high cytogenetic risk group (ATG vs. non-ATG; 29.7% vs. 20.6%, p = 0.225; 8.4% vs. 4.4%, p = 0.635, Figure A-4,5). In the subgroup analysis of patients with high cytogenetic risk, although there was no statistical significance, the ATG group showed a trend towards decreased 1-year CI of chronic GVHD and higher cGRFS compared to the non-ATG group (10.4% vs. 40.0%, p = 0.342; 31.2% vs. 16.7%, p = 0.929, Figure B-2,3). However, the ATG group exhibited a significantly higher 1-year CI of relapse compared to the non-ATG group (60.0% vs. 16.7%, p = 0.019, Figure B-4). In conclusion, our study findings indicate that ATG was effective in preventing chronic GVHD and demonstrated higher cGRFS in AML patients undergoing matched sibling donor HSCT. However, AML patients with high cytogenetic risk should carefully consider the use of ATG due to the associated higher risk of relapse. Further investigations are warranted to validate these findings and determine the appropriate dosage of ATG for high cytogenetic risk AML patients.

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 Premedication Prior to Platelet Transfusion on Platelet Increment Among Hemato-Oncological Patients

Introduction: Platelet transfusions have reduced the incidence of major hemorrhagic complications among hemato-oncological patients, however they are associated with potential complications, including transfusion reactions. The efficacy of premedication with steroids and/or antihistamines prior to platelet transfusion in preventing transfusion reactions has been studied. However, to the best of our knowledge, the effect of premedication on platelet increment has not been previously addressed. We aimed to assess the impact of premedication on platelet increment after platelet transfusion. Methods: We conducted a prospective study among adult patients admitted to the hemato-oncology and bone marrow transplantation (BMT) units in a tertiary medical center. Enrolled patients, who received a platelet transfusion during their admission, had a complete blood count taken 1-hour post platelet transfusion completion. The decision whether to administer premedication and the specific medications were left to the discretion of the attending physician. Single donor platelets or 5 pooled random donor platelets were provided by the blood bank interchangeably according to inventory level. The primary outcome was platelet recovery, defined as the difference between the 1-hour post- and pre- transfusion platelet counts. Adequate platelet recovery was considered &amp;gt;10,000/µL. Secondary outcome was platelet survival, defined as the difference between platelet count 18- to 24-hours post- and pre- transfusion. Rates of post-transfusion reactions and premedication complications were recorded. Association of other clinical variables with outcomes of interest was evaluated and variables significantly associated with adequate platelet recovery response (p&amp;lt;0.05) were entered into a multivariable analysis. Results: Overall, 68 patients were enrolled, with a median age of 58 years (interquartile range [IQR] 45-67) and 43 (63%) were males. The most common diagnoses were AML (n=24, 35%) and multiple myeloma (n=23, 34%). Most patients (72%) were admitted for a BMT (autologous 47%, allogeneic 25%). Outcomes were recorded in response to 217 platelet transfusions, with a median number of platelet transfusion per patient of 4 (IQR 3-5). Premedication was given prior to 64 transfusions (29%), consisting of steroids in 17 (27%), antihistamines in 4 (6%), or both in 43 (67%) platelet transfusions. In 153 (71%) platelet transfusions, no premedication was given. Patients who received premedication were younger, more often had a diagnosis of acute leukemia and were mostly admitted for non-transplant admissions. ( Table 1). Median platelet recovery and survival for all platelet transfusions were 15,000/µL (IQR 10,0000-22,500/µL) and 8,000/µL (IQR 4000-14,000/µL), respectively. There was no significant difference in median platelet recovery and survival between patients who received premedication and those who did not (15,000/µL in both cohorts, p=0.36 and 6,500 vs. 9,000/µL, p=0.69, respectively). The number of platelet transfusions leading to adequate platelet recovery was 150/213 (70.4%) overall, with no significant difference between patients who received premedication and those who did not [45/64 (70.3%) vs.105/153 (70.5%), p=1.0]. Female gender was associated with a higher rate of adequate platelet response in univariate analysis (81.7% vs. 63.4%, p=0.006), while splenomegaly was associated with a trend towards lower rates of adequate platelet recovery (55.2% vs. 71.4%, p=0.086). None of these variables was associated with adequate platelet recovery in multivariate analysis. Febrile non-hemolytic transfusion reaction (FNHTR) was significantly more common after platelet transfusions without premedication compared to platelet transfusions with premedication (7.8% vs. 0%, respectively, p=0.02). Among patients who received premedication, only one patient developed grade 2 asymptomatic hyperglycemia. Conclusions: To the best of our knowledge, this is the first prospective study to assess the impact of premedication prior to platelet transfusion on platelet recovery and survival. We did not observe an effect of premedication on various parameters of platelet increment, while use of premedication did reduce FNHTR. Our results suggest that premedication with steroids and/or antihistamines can be given prior to platelet transfusion without compromising platelet increment.

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, &amp; 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 &amp;lt; 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.