Kaplan-Meier Log-rank Analysis Research Articles

Influence of preemptive analgesia with etoricoxib on three types of pain after extraction of impacted teeth

Objective: To evaluate the effect of preventive use of etocoxib-induced preemptive analgesia on three types of pain (wound pain, swallowing pain, mouth opening pain) after extraction of impacted teeth. Methods: In this study, 60 patients (60 teeth) with impacted mandibular third molars in Department of Jinyintan Outpatient, School of Stomatology, Wuhan University from May to October 2020 were enrolled. The patients were numbered by SPSS 21.0 and randomly divided into two groups. The odd number was included in the etocoxib group, and the even number was included in the control group, with 30 cases in each group. Patients in the two groups were given etocoxib 60 mg or placebo vitamin C 100 mg 30 min before operation. Pain at 2, 4, 6, 8, 10, 12, and 24 hours after tooth extraction was recorded with numeric rating scale (NRS) score. The total dose of ibuprofen rescue intake was recorded. Kaplan-Meier curves and Log-Rank analyses were used to evaluate the proportion of patients without rescue analgesic. Results: The NRS scores of wound pain, swallowing pain and mouth opening pain in the etoricoxib group were lower than those in the control group within 24 hours after tooth extraction (P<0.05). The total dose of emergency analgesics in the etoricoxib group [(0.7±0.7) dose] was lower than that in the control group [(1.4±0.9) dose] (P<0.01). The mean time between first application of analgesics was 11.5 hours in etoricoxib group and 3.5 hours in the placebo group, respectively (P<0.05). Conclusions: This study revealed that etoricoxib has a substantial preemptive analgesic effect, resulting in the reduced use of analgesics after third molar removal.

Determinants of Survival in Skull Base Osteosarcoma: A National Cancer Database Study

Skull base osteosarcoma is a rare and aggressive tumor that is most commonly treated with primary surgical resection and adjuvant chemoradiation. Using the National Cancer Database, we analyzed demographic and clinical prognosticators for overall survival (OS). The National Cancer Database was queried for cases of histologically confirmed skull base osteosarcoma treated between 2004 and 2015, excluding patients receiving palliation or having <1 month of follow-up. A total of 314 patients treated with surgery alone (n= 82), surgery with adjuvant radiotherapy (n= 35), surgery with chemotherapy (n= 114), or trimodality therapy (n= 56) were identified. The χ2 test for categorical variables, Cox proportional hazards models, and Kaplan-Meier log-rank analysis were used to test associations with treatment, OS, and survival time. None of the studied demographic characteristics (age, sex, race, overall health) and socioeconomic factors (income and average regional education) were associated with OS (none P < 0.05). Treatment modalities also did not show a significant association with OS (none P < 0.05). Certain tumor characteristics showed an association with OS, with fibroblastic and Paget histologic subtypes (each P= 0.003), poorly differentiated tumor grade (P= 0.03), and tumor size >5 cm (P= 0.045) associated with poorer OS. Tumor histologic subtype, advanced tumor grade, and greater tumor size are predictors of worse OS in skull base osteosarcoma. No significant differences in OS were identified based on treatment modality, which warrants further investigation.

Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients.

Simple SummaryGlioblastoma (GBM) is one of the most common and most aggressive brain tumors with higher prevalence among men than women. Loss of chromosome Y (LOY) in the peripheral blood cells has been associated with increased risk of developing cancer. However, there is a lack of data about LOY in GBM tumor tissue and the potential impact on patients’ prognosis. Through droplet digital PCR (ddPCR) analysis of 10 markers spread throughout chromosome Y in 105 male GBM patients, we were able to identify deletion of SRY gene as a factor strongly correlating with reduced overall survival. This finding was later corroborated by the analysis of GBM gene expression data collected in TCGA, showing correlation between decreased SRY expression and shortened overall survival.Background: Biological causes of sex disparity seen in the prevalence of cancer, including glioblastoma (GBM), remain poorly understood. One of the considered aspects is the involvement of the sex chromosomes, especially loss of chromosome Y (LOY). Methods: Tumors from 105 isocitrate dehydrogenase (IDH) wild type male GBM patients were tested with droplet digital PCR for copy number changes of ten genes on chromosome Y. Decreased gene expression, a proxy of gene loss, was then analyzed in 225 IDH wild type GBM derived from TCGA and overall survival in both cohorts was tested with Kaplan–Meier log-rank analysis and maximally selected rank statistics for cut-off determination. Results: LOY was associated with significantly shorter overall survival (7 vs. 14.6 months, p = 0.0016), and among investigated individual genes survival correlated most prominently with loss of the sex-determining region Y gene (SRY) (10.8 vs. 14.8 months, p = 0.0031). Gene set enrichment analysis revealed that epidermal growth factor receptor, platelet-derived growth factor receptor, and MYC proto-oncogene signaling pathways are associated with low SRY expression. Conclusion: Our data show that deletions and reduced gene expression of chromosome Y genes, especially SRY, are associated with reduced survival of male GBM patients and connected to major susceptibility pathways of gliomagenesis.

Determination of tumour dose response threshold and implication on survival in patients with HCC treated with Y90 radiation segmentectomy: a simple semi-quantitative analysis.

To evaluate the relationship between Yttrium-90 (Y90) tumour dose and response rate in patients with hepatocellular carcinoma (HCC) who undergo Y90 radiation segmentectomy (Y90-RS) and to determine implication on overall survival (OS). Post Y90-RS Bremsstrahlung single-photon emission computed tomography/CT of 105 HCC patients with 110 treatments performed with glass microspheres was retrospectively analysed. The dose-volume histogram of the targeted tumour was determined with commercially available dosimetry software. Tumour response at 3 months was evaluated using modified Response Evaluation Criteria in Solid Tumours. Tumour dose thresholds associated with the objective response with 80% specificity were then used to evaluate implication on OS using Kaplan-Meier estimation and log-rank analysis. Tumour dose thresholds to predict objective response with 80% specificity were the following: maximum tumour dose (748 Gy), mean tumour dose (568 Gy), minimum tumour dose of 30% tumour volume (608 Gy), minimum tumour dose of 50% tumour volume (565 Gy), minimum tumour dose of 70% tumour volume (464 Gy) and minimum tumour dose of 100% tumour volume (213 Gy). These parameters all significantly predicted tumour response with areas under the ROC curve of >0.6. Mean tumour dose of ≥250 Gy predicted median OS of 43.67 vs. 17.87 months for others (P = 0.026). Minimum dose ≥180 Gy to 100% of tumour volume predicted median OS of 44.93 vs. 35.87 months for others (P = 0.043). In patients with HCC undergoing Y90-RS, mean tumour dose ≥250 Gy and minimum tumour dose of ≥180 Gy to 100% of tumour volume are both significantly correlated with higher objective tumour response and prolonged survival.

P76.75 Clinical Outcome and Toxicity Profiles of Patients with EGFR-mutation Positive Non-Small-Cell Lung Cancer

Activating mutations of EGFR in advanced lung adenocarcinoma and its inhibition with specific tyrosine kinase inhibitors has been shown to generate clinically significant tumor responses. Treatment outcomes of advanced EGFR mutant lung carcinoma in Pakistani population are not previously reported. We conducted a study using the Real World Data (RWD) in patients with EGFR mutant advanced lung cancer treated at our institution. We evaluated clinical features, toxicity profile and outcome of these patients and compared it with those who were unable to receive TKI due to resource limitations. We identified 27 patients with advanced lung cancer harboring EGFR mutations that were treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from January 2013 till April 2020. EGFR mutation detection was achieved by real time PCR. Data were collected through electronic medical record. Five patients were excluded from the analysis as they did not start treatment and were lost to follow-up. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves and log-rank analysis. Of the 22 patients analyzed, 54.5% were males and 45.5% were females. Twenty patients (90.9%) presented with de novo stage IV disease. Age ranged from 34-84 years. Frequency of Exon 19 deletion, Exon 21 L858R mutation, Exon18G7196 mutation and Exon 20 mutation was 50%, 32%, 9% and 4.5% respectively. One patient had compound Exon18G719X and Exon20S7681 mutation. 18.2% of patients had CNS metastasis at initial presentation. We identified 4 groups in our patient population. Group-1 consisted of patients who received first-generation TKI followed by third-generation TKI upon progression. Group-2 consisted of patients who received upfront first-generation TKI followed by chemotherapy upon progression. Group-3 consisted of patients who received upfront chemotherapy followed by a first-generation TKI upon progression and Group-4 consisted of patients who received upfront chemotherapy followed by second-line chemotherapy upon progression. These groups reflect the real world issues of TKI affordability in a Low Middle Income country (LMIC) such as Pakistan. Median PFS on first-line treatment (PFS1) was 10.7 months in the upfront chemotherapy group, versus 14.5 months in the upfront TKI group (p-value = 0.280). Median PFS on second-line treatment (PFS2) was 4.4 months in the chemotherapy group versus 23.7 months in the TKI group (p-value = 0.001). Median OS in Group 2, 3 and 4 was 20.0, 85.6 and 26.0 months respectively and not yet reached in Group 1 (p = 0.271). 27.8% patients developed grade I-II skin rash and diarrhea, 5.6% developed grade III-IV anemia, grade I-II neutropenia, and grade III-IV hyperbilirubinemia Within the constraints of a small sample size our real world data shows that the use of EGFR TKI in advanced EGFR mutant lung cancer is well tolerated in a Pakistani population. Use of EGFR TKI yields a superior PFS in both upfront and subsequent line of therapy which is consistent with the previously reported data. Preliminary overall survival favors superior outcome in the TKI group compared to chemotherapy alone or chemo-TKI combination groups.

Does the diagnostic modality for upper tract urothelial carcinoma prior to radical nephroureterectomy influence the risk of subsequent intravesical recurrence?

405 Background: The diagnosis of upper tract urothelial carcinoma (UTUC) is frequently obtained via diagnostic ureteroscopy (URS) with biopsy. In a recent meta-analysis of five retrospective series comparing UTUC RNU patients with and without prior diagnostic URS, prior URS was associated with intravesical recurrence of urothelial carcinoma. However, there remains an incomplete understanding of the risks of URS on intravesical recurrence after RNU, and existing studies have not examined the risks of URS without endoscopic biopsy or percutaneous biopsy alone. Here, we query our institutional RNU registry to determine if UTUC diagnostic modality influences post-RNU intravesical recurrence risk. Methods: Years 1995 to 2019 of our institutions RNU registry were queried. Patients with UTUC were divided into four groups: 1) URS with endoscopic biopsy; 2) URS without endoscopic biopsy (visual confirmation alone); 3) percutaneous biopsy without any URS; 4) no URS and no percutaneous biopsy. Exclusion criteria included pure non-urothelial histology, RNU for benign indications, and prior/concomitant cystectomy. The primary outcome was intravesical recurrence of urothelial carcinoma compared across the four groups using Kaplan-Meier log-rank analyses and Cox-proportional hazard modeling (hazard ratio = HR). Results: In a cohort of 878 patients (mean post-RNU follow-up 43 months), 461 (53%) had URS with biopsy, 130 (15%) had URS without biopsy, 229 (26%) had no URS or percutaneous biopsy, and 58 (7%) had percutaneous biopsy alone. The 3-year intravesical recurrence rate was 27%, 22%, 18%, 12% for groups 1-4, respectively. Covariates associated with intravesical recurrence on univariable analysis included age (HR 1.03, p &lt; 0.01), female gender (HR 0.76, p = 0.06), history of bladder cancer (HR 1.39, p = 0.01), current smoker (HR 1.49, p = 0.04), and multifocality (HR 1.34, p = 0.03). After adjusting for these covariates, multivariable analysis found that group 1 (URS with biopsy) was associated with increased intravesical recurrence (HR 1.41, p = 0.03) relative to group 3 (no URS or percutaneous biopsy). Compared to group 1, the hazard ratio for intravesical recurrence was not significantly different for group 2 (HR 1.18, p = 0.45) or group 4 (HR 1.11, p = 0.79). Conclusions: Patients undergoing ureteroscopic biopsy to diagnose UTUC prior to RNU had a higher risk of intravesical recurrence after RNU compared to patients who did not undergo any URS or percutaneous biopsy. This agrees with prior literature and suggests that aggressive ureteroscopic manipulation of UTUC tumors via biopsy may promote shedding of urothelial carcinoma cells capable of seeding the bladder. Our study does support the initiation of a randomized trial to determine if intravesical chemotherapy after ureteroscopic biopsy can reduce intravesical urothelial carcinoma recurrences.

Fifteen-MiRNA-Based Signature Is a Reliable Prognosis-Predicting Tool for Prostate Cancer Patients.

Recurrence is a major problem for prostate cancer patients, thus, identifying prognosis-related markers to evaluate clinical outcomes is essential. Here, we established a fifteen-miRNA-based recurrence-free survival (RFS) predicting signature based on the miRNA expression profile extracted from The Cancer Genome Atlas (TCGA) database by the LASSO Cox regression analysis. The median risk score generated by the signature in both the TCGA training and the external Memorial Sloan-Kettering Cancer Center (MSKCC) validation cohorts was employed and the patients were subclassified into low- and high-risk subgroups. The Kaplan-Meier plot and log-rank analyses showed significant survival differences between low- and high-risk subgroups of patients (TCGA, log-rank P < 0.001 & MSKCC, log-rank P = 0.045). In addition, the receiver operating characteristic curves of both the training and external validation cohorts indicated the good performance of our model. After predicting the downstream genes of these miRNAs, the miRNA-mRNA network was visualized by Cytoscape software. In addition, pathway analyses found that the differences between two groups were mainly enriched on tumor progression and drug resistance-related pathways. Multivariate analyses revealed that the miRNA signature is an independent indicator of RFS prognosis for prostate cancer patients with or without clinicopathological features. In summary, our novel fifteen-miRNA-based prediction signature is a reliable method to evaluate the prognosis of prostate cancer patients.

Treatment Analysis and Overall Survival Outcomes of Patients With Bilateral Vestibular Schwannoma.

To investigate the clinical presentation, treatment breakdown, and overall survival (OS) outcomes of patients with neurofibromatosis type 2 (NF2)-associated bilateral vestibular schwannoma (NVS). The 2004 to 2016 National Cancer Database was queried for patients with a diagnosis of VS. The "Laterality" code was used to stratify patients into sporadic unilateral vestibular schwannoma (UVS) and NVS. Of the 33,839 patients with VS, 155 (0.46%) were coded for NVS with an average age and tumor size of 37.4 ± 20.5 years and 23.5 ± 18.2 mm. Patients underwent observation (45.3%), surgery (29.3%), and radiotherapy (20.0%), and had a 5.8% 5-year mortality rate. Compared with UVS, NVS was negatively associated with receiving surgery (40.2% versus 29.3%, p = 0.02) while watchful observation was more prevalent (30.1% versus 45.3%, p = 0.001). In NVS, undergoing surgery was associated with larger tumor size (34.5 ± 21.2 versus 17.8 ± 13.3 mm, p = 0.001) and shorter diagnosis-to-treatment time (49.1 ± 60.6 versus 87.0 ± 78.5 d, p = 0.02), radiotherapy was associated with older age (44.4 ± 18.9 versus 35.2 ± 20.6 yr, p = 0.02) and longer diagnosis-to-treatment time (85.9 ± 77.9 versus 53.9 ± 65.5 d, p = 0.04), and observation was associated with smaller tumor size (17.8 ± 15.9 versus 28.0 ± 19.2 mm, p = 0.01). Kaplan-Meier log-rank analysis demonstrated similar 10-year OS between NVS and UVS patients (p = 0.58) without factoring the earlier age of presentation. Furthermore, there were no temporal changes in presentation/management of NVS, and OS was not dependent on the received treatment (p = 0.30). With younger age, larger tumors, and more conservative management, NVS's OS was not treatment-dependent and was similar to sporadic UVS, though the latter should not be interpreted as similar life expectancies due to the much earlier presentation.

Prognostic Factors and Long-Term Survival in Locally Advanced NSCLC with Pathological Complete Response after Surgical Resection Following Neoadjuvant Therapy.

Simple SummaryHigher response may be achieved with induction therapy (IT) and better survival results could be expected after complete surgical resection for non-small-cell lung cancer (NSCLC) patients. Thus, locally advanced (LA)-NSCLC patients with pathological complete response (pCR) are optimal candidates to undergo surgery after IT, achieving good to very good long-term survival. Herein, we performed a retrospective analysis on a large cohort of locally advanced NSCLC patients who achieved pCR after IT and surgery, exploring long-term survival and factors affecting prognosis. We observed a rewarding 5-year overall survival (56%) with baseline N2 single-station disease and adjuvant therapy after surgery associated with better prognosis. These findings may be useful to better define the strategy of care in this highly selected subset of NSCLC patients.Background: Outcomes for locally advanced NSCLC with pathological complete response (pCR), i.e., pT0N0 after induction chemoradiotherapy (IT), have been seldom investigated. Herein, long-term results, in this highly selected group of patients, have been evaluated with the aim to identify prognostic predictive factors. Methods: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent IT, possibly following surgery, from January 1992 to December 2019, were considered for this retrospective analysis. Survival rates and prognostic factors have been studied with Kaplan-Meier analysis, log-rank and Cox regression analysis. Results: Three-hundred and forty-three consecutive patients underwent IT in the considered period. Out of them, 279 were addressed to surgery; among them, pCR has been observed in 62 patients (18% of the total and 22% of the operated patients). In the pCR-group, clinical staging was IIb in 3 (5%) patients, IIIa in 28 (45%) patients and IIIb in 31 (50%). Surgery consisted of (bi)lobectomy in the majority of cases (80.7%), followed by pneumonectomy (19.3%). Adjuvant therapy was administered in 33 (53.2%) patients. Five-year overall survival and disease-free survival have been respectively 56.18% and 48.84%. The relative risk of death, observed with the Cox regression analysis, was 4.4 times higher (95% confidence interval (CI): 1.632–11.695, p = 0.03) for patients with N2 multi-station disease, 2.6 times higher (95% CI: 1.066–6.407, p = 0.036) for patients treated with pneumonectomy and 3 times higher (95% CI: 1.302–6.809, p = 0.01) for patients who did not receive adjuvant therapy. Conclusions: Rewarding long-term results could be expected in locally advanced NSCLC patients with pCR after IT followed by surgery. Baseline N2 single-station disease and adjuvant therapy after surgery seem to be associated with better prognosis, while pneumonectomy is associated with poorer outcomes.

MDS-372: TP53 Mutated del(5q) Myelodysplastic Syndromes (MDS) Patients Have Survivals Comparable to Those with TP53 Wild-Type

Background: TP53 mutations confer dismal prognosis in many hematologic malignancies, including MDS in general. It is frequently found in higher-risk/therapy-related MDS. However, 15-20% can occur in patients with del(5q), a subgroup that is known to have a more favorable risk. A prior study suggests TP53 mutations are associated with worse outcomes in del(5q) MDS. Objective: To assess the prognostic impact of TP53 mutations in del(5q) MDS patients and to report response to lenalidomide. Methods: This is a retrospective study of del(5q) MDS patients who were treated at the Moffitt Cancer Center from 2001 to 2019. Out of 132 patients identified, 63 had molecular data available and represent the cohort of present study. Univariate (log-rank), multivariate (Cox regression), and Kaplan-Meier (log-rank) analyses were performed. Results: Of the 63 patients (26M/37F), 23.8% were found to have TP53 mutation. Majority had isolated del(5q) (85%) with the remaining del(5q) plus other aberration(s) but not meeting criteria as complex. A total of 43 patients (68.3%) received lenalidomide (73.3% TP53 MT and 66.7% TP53 WT, p=NS) with 37.2%, 55.8%, and 7% achieving HI, NR, and DP/death, respectively. AML transformation occurred in 14.3% (20% TP53 MT and 12.5% TP53 WT, p=NS). Other common mutations include TET2 (19%), DNMT3A (17%), and SF3B1 (10%). The median OS was 76.6 months (median follow-up: 71.3 months). There was no significant difference in OS regardless of TP53 mutational status (p=0.72). Among patients who received lenalidomide, mOS for HI, NR, and DP/death were 142.2, 66, and 25.6 months, respectively (p ≤ 0.001). Univariate analysis showed lenalidomide response significantly impacted OS (HI:HR 0.02, 95% CI: 0.00-0.11, p ≤ 0.001; NR:HR 0.08, 95% CI: 0.02-0.43, p=0.003). Multivariate regression using covariates including TP53 status confirmed lenalidomide response to be independently associated with outcomes. Conclusions: There was no significant difference in OS in patients with TP53 MT vs. TP53 WT. A substantial portion of del(5q) MDS patients benefited from lenalidomide. Despite the known overall adverse association between TP53 and MDS, our data suggests the del(5q) subset behaves differently, which adds to the heterogeneity of the disease. Further studies are needed to clarify the impact of treatments and somatic mutations on outcomes.

Values of long noncoding RNA SAMMSON in the clinicopathologic features and the prognostic implications of human gastric cancer.

The aim of this study was to explore the clinical significance of lncRNA-survival associated mitochondrial melanoma-specific oncogenic non-coding RNA (lncRNA-SAMMSON) in the development and clinicopathological parameters of gastric cancer (GC). Tissue specimens were collected from GC patients who received treatment in our hospital. Real-time quantitative polymerase chain reaction (QRT-PCR) was used to determine lncRNA-SAMMSON expression. Small interfering RNA (siRNA) was transfected to suppress the expression of lncRNA-SAMMSON in vitro. Pearson's χ2-test was used to investigate the interaction of lncRNA-SAMMSON with clinicopathological parameters of GC patients. Kaplan-Meier method and Log rank analysis were used to analyze the progression-free survival time and overall time of GC patients. Furthermore, transwell assay and wound healing assay were conducted to determine the invasion and migration abilities of GC cells, respectively. QRT-PCR results showed that lncRNA-SAMMSON was abnormally overexpressed in GC tissues and cells (p<0.05). Pearson's χ2-test illustrated that clinical stage, distant metastasis and lymph node metastasis were closely related to lncRNA-SAMMSON expression in GC patients (p<0.05). Kaplan-Meier survival analysis represented that GC patients with high lncRNA-SAMMSON expression had significantly shorter progression-free survival time and overall survival time (p<0.05). Transwell assay and wound healing assay proved that inhibition of lncRNA-SAMMSON in GC cells dramatically reduced the invasion and migration abilities of GC cells, respectively (p<0.05). LncRNA-SAMMSON played an important role in the development of GC, which might be regarded as a new target for the diagnosis and treatment of GC.

Elevated CISD2 expression predicts poor diagnosis and promotes invasion and migration of prostate cancer cells.

To explore roles of CDGSH iron-sulfur domain-containing protein 2 (CISD2) in the progression of prostate cancer (PCa) cells, and relationships between CISD2 expression and the prognosis and clinical pathological parameters in PCa patients. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis and Western blot analysis were used to detect the CISD2 expression in PCa tissues and cells. CISD2 siRNA was used to inhibit the CISD2 expression. Kaplan-Meier method and Log rank analysis were performed to determine survival analysis while Chi-square test was performed to analyze the association between CISD2 and clinicopathological parameters of PCa patients. Transwell assay and wound healing assay was conducted to examine the invasion and migration ability of PCa cells, respectively. CISD2 was up-regulated in PCa tissues and cells, and showed positive association with the poor prognosis, T stage, lymphatic invasion, prostate-specific antigen (PSA) level, and distant metastasis of PCa patients. Besides, we found that inhibition of CISD2 significantly impaired the migration and invasion ability of PCa cells. The paper demonstrated that CISD2 could act as a new target for the diagnosis and treatment of PCa patients.

A Contemporary Analysis of the Safety and Efficacy of Cardiac Transplantation from Donors with Blood Infections

Consideration of cardiac allografts from donors with blood infections (DBI) varies widely across institutions and providers. While often discarded due to concern for infectious complications in immunocompromised recipients, these organs may represent a possible source for addressing prolonged waitlist times. Existing evidence in the literature is from prior decades; consequently, we sought to analyze the outcomes of recipients of DBI hearts using contemporary data. We identified first-time, adult recipients of cardiac transplants from 2010 to 2018 using the OPTN/UNOS Standard Transplant Analysis and Research Files. Patients were classified by receipt of an organ from DBI versus those from a donor with no documented blood infection (control cohort). Information about culprit pathogen and antimicrobial therapy was not available in this dataset. Overall survival was compared using Kaplan-Meier log-rank analysis. Predictors of mortality were assessed using a Cox proportional-hazards model. From 2010 to 2018, 22,834 heart transplants met inclusion criteria, of which 1,982 (8.7%) involved a donor with a blood infection. Recipients were comparable in terms of age, sex, race, diagnosis, history of diabetes, serum creatinine, and proportion with mechanical circulatory support devices. Donors with blood infections were significantly older (29 vs. 28, p=0.01) and more likely to have diabetes (4% vs. 3%, p=0.02). DBI and control cohorts experienced equivalent length of index stay (16 vs. 56.5 days, p=0.051) and rates of rejection requiring treatment over their first year (p=0.40). Overall survival was equivalent (p=0.69) between DBI and control groups. Of note, Cox regression analysis revealed that blood infection was not predictive of mortality (HR 1.00, p=0.98). Predictors of mortality included age over 60 (HR 1.3, p<0.001), black race (HR 1.2, p<0.001), BMI > 30 (HR 1.2, p<0.001), history of diabetes (HR 1.3, p<0.001), ECMO at time of transplant (HR 2.4, p<0.001), donor age (HR 1.1, p<0.001), and graft ischemia time (HR 1.1, p<0.001). Adults who received first-time heart transplants from donors with blood infections from 2010 to 2018 experienced survival equivalent to controls. Although clinical judgement remains paramount, our findings discourage disqualification of an allograft due to blood infection alone.

Using ESTIMATE algorithm to establish an 8-mRNA signature prognosis prediction system and identify immunocyte infiltration-related genes in Pancreatic adenocarcinoma.

Objective: The tumour microenvironment is one of the significant factors driving the carcinogenesis of Pancreatic adenocarcinoma (PAAD). However, the underlying mechanism of how the tumour microenvironment impacts the prognosis of PAAD is not completely clear.Results: The transcriptome and clinical data of 182 PAAD program cases were downloaded from the TCGA database. Three hundred thirty-three differentially expressed genes (DEGs) between high and low stromal groups and 314 DEGs between high and low immune score groups were identified using ESTIMATE score. Based on the 203 genes differentially expressed simultaneously in two score-related comparisons, we established an 8-mRNA signature to evaluate the prognosis of PAAD patients. Kaplan-Meier curves showed significantly worse survival for patients with high-risk scores in both the training and validation groups. The risk score was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. By searching the TCGA database, we showed that CA9, CXCL9, and GIMAP7 from the 8-mRNA signature were associated with the infiltration levels of immunocytes by regulating FOXO1 expression in PAAD.Conclusions: Unlike traditional methods of screening for differential genes in cancer and healthy tissues, we constructed a novel 8-mRNA signature to predict the prognosis of PAAD patients by applying ESTIMATE scoring to RNA-seq-based transcriptome data. Most importantly, we identified CA9, CXCL9, and GIMAP7 from the above eight genes as regulators of immunocyte infiltration by adjusting the expression of FOXO1 in PAAD. Thus, CA9, CXCL9, and GIMAP7 might be the ideal targets of immune therapy of PAAD.Methods: ESTIMATE scoring was used to determine the stromal and immune scores of transcriptome datasets downloaded from the TCGA database. An mRNA-based prognostic signature was built for the training cohort via the LASSO Cox regression model. The signature was verified using a validation cohort. Kaplan-Meier curves and log-rank analysis were used to identify survival differences. Western blot analysis and RT-qPCR analysis were carried out to analyze the expression of specific proteins and mRNAs. IHC was performed to assess the protein levels of Forkhead box-O 1 (FOXO1), Carbonic anhydrase 9 (CA9), C-X-C motif chemokine ligand 9 (CXCL9), and GTPase, IMAP family member 7 (GIMAP7) in the tissue microarray of PAAD.

Abstract B49: The association between IKKα, immunologic markers, and clinical outcomes in patients with ER-positive tamoxifen-treated breast cancer

Abstract Background: Endocrine therapy is the standard of care for patients with estrogen receptor (ER)-positive breast cancer. However, endocrine therapy resistance is still a significant challenge for clinical practice. Nuclear factor Kappa B (NF-KB) is one of the most extensively studied pathways that has been demonstrated as a critical component in the endocrine resistance mechanism. In addition, NF-KB is a crucial factor that induces PD-L1 stabilization, resulting in enhancement of tumor immune evasion and potentially leading to endocrine therapy resistance. Studies that investigate correlations between NF-KB pathway and immunologic markers are limited. Therefore, the present study aims to examine the association between IKKα, a critical kinase in the NF-KB pathway, PD-1/PD-L1, and clinical outcomes in patient with ER-positive tamoxifen-treated breast cancer. Methods: Immunohistochemistry was performed to examine IKKα, IKKα phosphorylated at threonine 23 (p-IKKαT23) or serine 176 (p-IKKαS176), PD-L1, and PD-1 on a tissue microarray of the patients with early-stage ER-positive breast cancer. The median value was used as the cut-off point to determine low or high expression. Kaplan-Meier curves and log-rank analysis were used to analyze an association between these markers and clinical outcomes in terms of cancer-specific survival (CSS), recurrence-free survival (RFS), and recurrence on tamoxifen (RoT). Result: A total of 392 patients were included. High cytoplasmic IKKα was significantly associated with decreased CSS (p=0.012), RFS (p=0.005), and RoT (p=0.010). High nuclear p-IKKα S176 was significantly associated with decrease RoT (p=0.010). High nuclear p-IKKαT23 was significantly associated with decreased CSS (p=0.023), RFS (p=0.036), and RoT (p=0.015). High PD-L1 on tumor cells was significantly associated with decreased CSS (p&amp;lt;0.001), RFS (p=0.001), and RoT (p&amp;lt;0.001). Interestingly, high expression of PD-1 on TIL significantly associated with improved CSS (p=0.001), RFS (p=0.003), and RoT (p = 0.005). Assessing combined expression of high cytoplasmic IKKα and PD-L1 showed associations with decreased CSS (p&amp;lt;0.001), decreased RFS (p&amp;lt;0.001), and decreased RoT (p&amp;lt;0.001). Combined high expression of nuclear p-IKKαT23 and PD-L1 was association with decreasde CSS (both low vs. both high, HR 4.632[1.744-12.303], p=0.001). Conclusion: Increased expression of cytoplasmic and phosphorylated IKKα, as well as PD-L1 was significantly associated with poor clinical outcomes. However, increased PD-1 was associated with improved outcomes. In addition, combined high expression of cytoplasmic IKKα or nuclear p-IKKαT23 and PD-L1 was also significantly associated with poor clinical outcomes, indicating that in the tumor cell, activation of NF-kB pathway together with activation of PD-L1 provide additional prognosis that associates with decreased clinical outcomes and therefore could be employed as a prognostic marker. Citation Format: Phungern Khongthong, Linsay Bennett, Jean Quinn, Elizabeth Mallon, Antonia Roseweir, Joanne Edwards. The association between IKKα, immunologic markers, and clinical outcomes in patients with ER-positive tamoxifen-treated breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B49.

Prognostic factors that affect survival outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223.

225 Background: Radium-223 (Ra-223) improved overall survival (OS) in men with mCRPC with predominantly bone metastases. We analyzed their survival outcomes to identify factors associated with prognosis for men treated with Ra-223. Methods: This was a retrospective study of men with mCRPC at Princess Margaret Cancer Centre treated with Ra-223. Demographics, disease characteristics, number of bone metastasis [ &lt; 6, 6-20, &gt; 20], laboratory results, number of Ra-223 doses, systemic treatment lines after radium-223, use of bone protecting agents (BPA) and survival outcomes were collected. OS and progression-free survival (PFS) were estimated by Kaplan-Meier (log-rank) analysis. Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) were used to evaluate patient and disease characteristics, number of Ra-223 doses and overall survival. Results: 114 men received Ra-223 between May 2015 and May 2018 with median age 75 years (range 53-93). Median radium doses was 5 (68 [59.6%] received &gt; 4 doses, 46 [40.4%] received ≤4 doses). Median baseline ALP 113.5 U/L (31-1121), median baseline Hb 118 g/L (69-153), median baseline PSA 70.2 ug/L (0.15-5275), median LDH 242 UL (82-1426). 58% had 6-20 bone metastases and 28% had &gt; 20 bone metastases. The median OS and PFS for men who received ≤4 doses vs &gt; 4 doses was 4.56 vs 19.8 months (HR = 8.4; 95%CI: 4.861-14.62; p≤ 0.0001) and 2.9 vs 7.45 months (HR = 4.6; 95%CI: 2.837 to 7.537; p≤ 0.0001) respectively. The baseline median ALP was (154 vs 98; p = 0.03) for men who received ≤4 doses vs &gt; 4 doses Ra-223. On UVA, ECOG 0-1 (HR = 0.33; p = 0.0003), baseline PSA &lt; 70 ug/L (HR = 0.51; p = 0.0023), LDH &lt; 250 U/L (HR 0.55; p = 0.0082), Hb &gt; 120 g/L(HR 0.46; p = 0.0004), ALP &lt; 150 U/l(HR 0.38; p ≤ 0.0001) and receipt of subsequent treatment after Ra-223 (HR = 0.33; p &lt; 0.0001) were associated with improved OS. On MVA, receipt of subsequent treatment, administration &gt; 4 cycles of Ra-223 and baseline ALP &lt; 150 U/L were associated with improved OS. Conclusions: Men who receive &gt; 4 cycles of Ra-223 have significantly better OS than those who receive ≤4 doses. Baseline ALP was independently associated with better OS and could be used to identify patients most likely to benefit from Ra-223.

P650 Outcomes of endoscopic balloon dilation for luminal strictures in Crohn’s disease

Abstract Background Luminal strictures are common complications of Crohn’s disease (CD). Endoscopic balloon dilation (EBD) is an alternative to surgery for CD strictures. (1–3). The aim of this study was to evaluate the EBD success rate and identify predictive factors in CD patients. Methods 27 consecutive patients with CD in whom EBD was performed at the outpatient clinic of Bern University Hospital were retrospectively included in this study. Clinical, laboratory and endoscopic data were collected from the patient files. Stricture characteristics, short-term procedure success, procedure-related complications, occurrence of surgery and long-term clinical endpoints were documented. Short-term procedure success was defined by the ability to pass an 11.5-mm-wide endoscope through the stricture after dilatation and the absence of any documented complications during a 1-week follow-up. Results The study population consisted of 27 patients with Crohn’s disease. A total of 41 dilations were performed. 61.5% of the patients were on biologic therapy. The short-term dilatation success rate was 60%. 48.1% of the patients required stricture related surgery during the follow-up. There were two procedure-related complications 0.08% (bleeding; asymptomatic perforation discovered during surgery). 33.3% were anastomotic strictures. The median increase in dilatation diameter during a single session was 6 mm (range, 3–12mm). 53.8% of the patients required multiple dilatations during the same endoscopic procedure. In the Kaplan–Meier log-rank analysis, anastomotic strictures (secondary) did show a trend toward a longer surgery-free survival after EBD (p = 0.057) (Figure1) Conclusion EBD is successful and safe in treating luminal strictures and in prevention of immediate surgery in a high proportion of CD patients, in particular for anastomotic stricture. References

Prognostic significance of combined Lymphocyte-monocyte Ratio and Tumor-associated Macrophages in Gastric Cancer Patients after Radical Resection

Background: Immune function is recognized as an important prognostic indicator in gastric cancer (GC). The relationship between the lymphocyte-monocyte ratio (LMR) and tumor-associated macrophage (TAM) has received far less attention.Methods: A total of 401 patients from a prospective trial (NCT02327481) were enrolled in this study. The relationships between the LMR, TAM, and clinicopathologic variables were analyzed using a Kaplan-Meier log-rank survival analysis, and multivariate Cox regression models were used to identify associations with recurrence-free survival (RFS) and overall survival (OS). The discriminatory power of the prognostic models for both RFS and OS were compared. The decision curve analysis was performed to compare the clinical utility of the prognostic models.Results: High LMR was observed in 81.5% of the 401 GC patients, and high TAM infiltration was observed in 45.9% of the patients. In a multivariate Cox analysis of all patients, LMR and TAM were both independent prognostic factors for RFS and OS. Patients with high TAM expression had similar mean LMR levels than patients with low TAM expression. Moreover, LMR appeared to lose its prognostic significance in patients with high TAM expression levels. Finally, the model that included the TAM had better predictive capability and clinical utility for both RFS and OS.Conclusions: Although LMR and TAM are both independent predictors of RFS and OS in resectable GC patients, LMR seem to attenuate its prognostic significance in patients with high TAM expression. This information may be helpful in the clinical management of patients with GC. Further external studies are warranted to confirm this hypothesis.

Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab.

BackgroundThe optimal treatment sequence for patients with advanced BRAF V600 mutant melanoma is unknown. BRAF/MEK inhibition (BRAF/MEKi), single agent anti‐PD‐1 (aPD‐1) antibodies and combination immune checkpoint inhibition with nivolumab and ipilimumab (niv/ipi) are all approved; however, they have not been prospectively compared. Therefore, we sought to compare overall survival of patients with advanced BRAF mutant melanoma treated with either front‐line BRAF/MEKi, aPD‐1, or niv/ipi.MethodsPatients with advanced BRAF mutant melanoma who had received BRAF/MEKi, niv/ipi, or aPD‐1 in the front‐line setting were identified from a nationwide database comprising de‐identified patient‐level structured and unstructured data derived from electronic health records. Survival was compared using Kaplan‐Meier curves and log‐rank analysis. Univariate and multivariate Cox regression models were used to measure the effect of front‐line treatment, age (>64 or not), LDH (elevated or not), and Eastern Cooperative Oncology Group (ECOG) performance status (>1 or not) on survival.ResultsFive hundred and sixty seven patients with advanced disease and treated with front‐line aPD‐1 (n = 162), BRAF/MEKi (n = 297) or niv/ipi (n = 108) were identified. With a median follow‐up of 22.4 months, median overall survival (OS) for patients treated with front‐line niv/ipi was not reached (NR) while median OS for patients treated with aPD‐1 or BRAF/MEKi was 39.5 months and 13.2 months, respectively. Front‐line treatment with PD‐1 and niv/ipi were associated with statistically longer survival than BRAF/MEKi in multivariate analyses.ConclusionsIn our real‐world retrospective analysis, patients with advanced BRAF mutant melanoma treated with front‐line niv/ipi or aPD‐1 had longer survival compared to those treated with front‐line BRAF/MEKi.

Comparison of Low Pre-Emptive Oral Doses of Celecoxib Versus Acetaminophen for Postoperative Pain Management After Third Molar Surgery: A Randomized Controlled Study

This study aimed to compare the pre-emptive analgesia of oral celecoxib with oral acetaminophen after surgical removal of the mandibular third molars. A randomized, double-blinded, placebo-controlled clinical trial was conducted to examine patients presenting with a mandibular third molar for extraction under local anesthesia. The participants were randomized to receive a preoperative oral dose of celecoxib or acetaminophen as the predictor variable. The primary outcome variable was postoperative pain measured on a visual analog scale at different time points. The secondary outcome variable was the amount of postoperative analgesic medication taken in both groups. Statistical analyses included descriptive statistics, the t test, and the Pearson χ2 test. Significance was set at P<.05. The overall survival (interval to the first intake of ibuprofen) of the patients in each group was evaluated using Kaplan-Meier curves and log-rank analyses. Sixty participants were randomly divided into either the celecoxib group or acetaminophen group. The postoperative pain scores in the celecoxib group were significantly lower than those in the acetaminophen group at 4, 6, 8, and 12hours (P=.008, P=.001, P=.021, and P=.011, respectively). The number of patients who did not require analgesics in the celecoxib group was less than that in the acetaminophen group (P=.018). The average amount of rescue analgesic medication in the celecoxib group (0.6±0.8 dose) was significantly lower than that in the acetaminophen group (1.3±1.0 doses) (P=.002). The Kaplan-Meier curve indicated that celecoxib resulted in long-term survival of the patients who did not receive rescue analgesic medication (P=.0055). Celecoxib exhibits a significant pre-emptive analgesic effect, thereby reducing the use of postoperative analgesics after removal of the third molar.