Cox Proportional Hazards Test Research Articles

Perioperative versus adjuvant therapy in resectable pancreas cancer.

703 Background: Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer death in the United States with a 5-year survival rate of 13%. Recurrence rates are high following resection and optimization of neoadjuvant and adjuvant therapy remains under investigation, with the hypothesis that neoadjuvant/perioperative therapy may convert borderline resectable tumors to resectable and prevent progression of micro-metastases in the postoperative setting. Our study evaluates patient outcomes and models predictive and prognostic markers to assist with clinical decision-making in consideration of neoadjuvant therapy for resectable and borderline resectable pancreatic cancers. Methods: We performed a single-institution retrospective analysis of patients who underwent pancreatic resection between January 1, 2016 and December 31, 2020 (n=532). We excluded patients with unresectable disease or a non-PDAC diagnosis. Analysis of the remaining patients (n=175) was performed using automated and manual chart review, basic statistical comparisons with T-tests or Chi-squared tests, Kaplan-Meier Survival analyses, and Cox Proportional Hazard Testing using intention to treat analysis. Results: There were no significant differences (p>0.05) the presenting demographics between the adjuvant (AJ, n=97) and neoadjuvant/perioperative (NP, n=76) groups. Patients were more likely to have a history of pancreatitis, a risk factor for PDAC development, in the NP group (p=0.0153). Patients in the AJ group included patients who ultimately did not receive the recommended adjuvant therapy for various reasons (n=25) and had overall worse performance status (p=0.004) and received less chemotherapy overall compared to the NP cohort (p=0.0003). Adjuvant therapy was more likely to be gemcitabine with capecitabine (n=37, p=0.0007) in the AJ group and gemcitabine with nab-paclitaxel (n=11, p=0.0018) in the NP group. In the neoadjuvant setting, 62% of patients received FOLFIRINOX and 28% received gemcitabine with nab-paclitaxel. Patients in the NP group were more likely to receive radiation (p=0016), including 6 patients who received neoadjuvant radiation. Median overall survival (33.9 [28.8-43.8] versus 38.2 [28.2-47.8] months) and progression free survival (21.1 [18.1-34.2] versus 16.6 [11.7-23.6] months) were not significantly different between the AJ and NP groups, respectively. Conclusions: These results demonstrate similar presenting characteristics between patients with resectable PDAC treated in a period when general practice shifted from adjuvant therapy to a neoadjuvant/perioperative approach. Although patients treated neoadjuvantly received more chemotherapy overall and the chemotherapy regimens differed between the groups, patients had similar outcomes in the two groups.

Cohort study on the Effect of various nicotine consumption modalities on Mohs surgery complications.

Knowledge on the effect of different nicotine consumption modalities on dermatologic surgical outcomes is limited, with conflicting conclusions. Cigarette smoking is known to adversely affect outcomes, but the impact of other nicotine consumption modalities like cigars, smokeless tobacco, and nicotine replacement therapy (NRT) is less understood. Our objective was to evaluate the impact of various nicotine consumption modalities on complication rates after Mohs micrographic surgery (MMS). We conducted a prospective cohort study of 404 MMS patients. Variables analyzed included patient age, sex, post-operative complications, and nicotine history via a questionnaire. We found that patients with any history of nicotine use had an 8.5% absolute risk of experiencing complications while the risk for patients without a history of nicotine use was 3.1%, representing a relative risk of 2.75. Cox proportional hazard testing found patient sex and past smoked tobacco use as statistically significant factors for complications. Patients who have smoked tobacco appear to be at a significantly increased risk of experiencing a complication following MMS compared to never-nicotine users. Larger studies are needed to clarify the surgical risks posed by smokeless nicotine products.

Changes in Blood Eosinophil Counts Predict the Death of Patients With Myocardial Infarction After Hospital Discharge.

Preclinical studies demonstrate a cardioprotective role of eosinophils in acute myocardial infarction. Yet clinical studies show conflicting correlations between blood eosinophil counts and acute myocardial infarction risk and mortality. This study evaluates blood eosinophil counts of patients with acute myocardial infarction at hospital admission (EOSbaseline) and discharge (EOSpost) on all-cause and cardiac mortalities. Of 2681 consecutive patients with a median follow-up of 2.55 years, 45 patients died within 30 days, 28 died within 30 to 150 days, and 92 died within 150 days or later postdischarge. Cardiac death occurred in 108 patients. According to the receiver operating characteristic analyses, the best cutoffs of EOSbaseline and EOSpost were 0.02×109/L and 0.03×109/L, respectively, to predict 30-day all-cause death (area under the curve [AUC]baseline, 0.60; AUCpost, 0.67). The optimal cutoffs of EOSbaseline and EOSpost were 0.20×109/L and 0.14×109/L to predict long-term all-cause mortality (1-year AUCbaseline, 0.59; 1-year AUCpost, 0.61). Multivariate logistic analysis showed that low EOSbaseline (<0.02×109/L) or low EOSpost (<0.03×109/L) predicted the 30-day all-cause (odds ratio [OR]baseline, 2.56; P=0.005; ORpost, 8.14; P<0.001) and cardiac (ORbaseline, 2.16; P=0.025; ORpost, 7.89; P<0.001) mortalities. Patients with combined low EOSbaseline (<0.02×109/L) and low EOSpost (<0.03×109/L) displayed synergistic risk of 30-day all-cause (OR, 13.93; P<0.001) and cardiac (OR, 11.38; P<0.001) deaths. In contrast, adjusted Cox proportional hazard test indicated that high EOSpost (≥0.14×109/L) was an independent risk for long-term all-cause mortality (hazard ratio, 1.84; P=0.010). High and low blood eosinophil counts both predict the risk of all-cause and cardiac deaths in patients with acute myocardial infarction depending on the time of data collection. Dynamic changes of blood eosinophil counts offer a more accurate prediction of post-myocardial infarction deaths than a single time point data analysis.

Utilization of special services among children and youth with special healthcare needs: A time-to-event analysis of the national survey of children's health data, 2016–2022

BackgroundSpecial services including physical, occupational, speech, or behavioral therapies are associated with enhanced long-term functioning and well-being of children and youth with special healthcare needs (CYSHCN). Yet, there is a lack of recent evidence on the utilization of these services, and the age at which CYSHCN first receive them. ObjectiveThis study assessed the distribution, timing, and determinants of special services utilization across different types of special healthcare needs. MethodsData from 63,734 caregivers of CYSHCN aged 0–17 years from the 2016–2022 National Survey of Children's Health were analyzed using Rao-Scott Chi-Square, Log-rank, and Cox proportional hazard tests. ResultsOverall, 41.9 % of CYSHCN ever received special services, including 91.4 %, 90.3 %, 88.0, and 34.1 % of children and youth with Down syndrome, cerebral palsy, autism, and other special healthcare needs (OSHCN), respectively. Children with Down syndrome and cerebral palsy received special services earlier than those with autism or OSHCN. Utilization of special services was higher among male children and youth (aHR 1.41; 95 % CI: 1.33–1.49), aged 0–5 years (aHR: 4.70; 95 % CI: 4.32–5.11), second or later born children (aHR: 1.18; 95 % CI: 1.10–1.26), from families with low-income (aHR: 1.14; 95 % CI: 1.04–1.24), living with married parents (aHR: 1.11; 95 % CI: 1.04–1.19), consistently insured (aHR: 1.24; 95 % CI: 1.08–1.42), and with a more complex health condition (aHR: 3.40; 95 % CI: 3.13–3.70) compared to their counterparts. ConclusionsThese findings highlight the necessity of adopting tailored approaches for children with different special healthcare needs to optimize and sustain the utilization of special services.

Factors associated with the receipt of palliative care in Native American patients with hepatocellular carcinoma: A retrospective analysis.

e16202 Background: Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related deaths in the United States. This primary liver malignancy often has a poor prognosis and commonly metastasizes to the lungs, lymph nodes, bones, and adrenal glands. HCC has a high burden of disease with many patients suffering from discomfort and pain related to the disease and its treatment. Palliative care is a unique form of specialized care that provides relief, increasing comfort, and quality of life to patients suffering from illness. Many studies note its effectiveness in helping patients at any point in their illness. Furthermore, recent studies have shown that Native Americans face barriers to receiving palliative and end of life care. Thus, this study aims to examine the factors associated with receipt of palliative care within Native American HCC patients. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 28 and statistical significance was set at α = 0.05. Results: Out of 1536 Native American patients with HCC, 92 (5.9%) received palliative care. Patients who received palliative care experienced shorter mean survival than those who did not receive palliative care (15 vs 42 months; p &lt; 0.001). After controlling for age, year of diagnosis, surgical status and adjuvant therapies, not receiving palliative care was associated with an independent decrease in hazard (HR = 0.625, p &lt; 0.05). Palliative care patients were more likely to present with stage III and IV HCC, experience a longer delay in receiving treatment (69 vs 48 days) and have bone and lung metastasis when compared to those who did not receive palliative care (p &lt; 0.05). Patients who did not receive palliative care were more likely to have Medicare or Medicaid for insurance (p &lt; 0.05). There were no significant differences in the age, income bracket, facility type, tumor size or time to surgery between the patients who received palliative care and those who did not. Conclusions: This study found that patients with HCC are more likely to utilize palliative care if they have severe disease that metastasized to other organ systems. There is a higher mortality among patients who receive palliative care most likely because they had more severe disease. This research demonstrates the common trend of HCC patients underutilizing palliative care in the early stages of disease. Exploring the impacts early palliative care can have on HCC patients’ survival and quality of life would be valuable future areas of research.

Longitudinal survival and complete tumor resection rates in Native American patients with hepatocellular carcinoma treated at academic institutions.

e16281 Background: Hepatocellular carcinoma (HCC) is the prevailing type of primary liver cancer, exhibited at a higher frequency in individuals afflicted by chronic liver conditions, notably cirrhosis induced by hepatitis B or hepatitis C infection. Past literature has demonstrated the impact certain socioeconomic factors (eg. race, occupation, place of residence) have on the prognosis of HCC, however the analysis of facility types where treatment was received in relation to HCC has yet to be further examined. Historically, Native American patients have exhibited a higher incidence of advanced-stage cancers at the time of diagnosis compared to white counterparts and experience the lowest cancer survival rates among all racial and ethnic groups. Using the NCDB, this study analyzed the relationship between the facility type where care was received and survival in Native American patients with HCC. Methods: The National Cancer Database (NCDB) was used to identify Native American patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: Of 1186 Native American patients included in the sample, 697 (45%) received treatment at an academic facility. Native American patients treated at academic facilities experienced greater survival as compared to those who were treated at nonacademic facilities (52 months vs 30 months, p &lt; 0.05). When controlling for age, year of diagnosis, surgical status, income bracket and surgical margins, receiving care at an academic facility was associated with an independent decrease in hazard (HR = 0.403; p &lt; 0.05). Native American patients who went to an academic facility were more likely present with Stage I and II tumors, receive surgery, have no residual tumor after surgery and have private insurance (p &lt; 0.05). Nonacademic facility patients, on the other hand, were more likely to present with Stage III and IV tumors, poorly differentiated and undifferentiated tumors, and have bone, brain, liver and lung metastases (p &lt; 0.05). No differences were seen in Charlson-Deyo score, adjuvant therapy type, or same hospital readmission within thirty days of hospital discharge. Conclusions: This study found that Native American patients with HCC who received treatment at academic facilities experienced improved overall survival. These results follow previous trends, wherein academic institutions may offer more specialized care or a greater spectrum of services that yield improved patient outcomes. Further research can explore other treatment differences that Native American HCC patients face and elucidate the cause of the disparity described here.

Factors associated with surgical intervention in Native American patients with hepatocellular carcinoma.

e16279 Background: Hepatocellular carcinoma (HCC) is the prevailing type of primary liver cancer, exhibited at a higher frequency in individuals afflicted by chronic liver conditions. Past literature has demonstrated the impact certain socioeconomic factors have on the prognosis of HCC. Native American patients often face late-stage cancer diagnoses and have the lowest survival rates among racial and ethnic groups. While surgery offers potential for cure, factors related to surgical interventions in liver cancer for Native American patients remain largely unexplored. Through the NCDB, this study analyzed factors associated with surgical intervention and survival trends in Native American patients with HCC. Methods: The National Cancer Database (NCDB) was used to identify Native American patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27, and statistical significance was set at α = 0.05. Results: Of 1193 Native American patients included in this sample, 172 (14.4%) patients received surgical treatment for HCC, while 1021 (85.6%) patients did not receive surgical treatment for HCC. Native American patients who received surgery for HCC experienced a greater mean overall survival (90 months) when compared to the mean overall survival (24 months) in HCC Native American patients who did not receive surgical treatments (p &lt; 0.001). When controlling for age, year of diagnosis, stage, grade, facility type and income status, receiving surgery showed an independent decrease in hazard (HR = 0.245; p &lt; 0.05). HCC Native American patients who received surgery were more likely to be treated an at academic facility, have stage I disease, and have less aggressive tumors (grade) (p &lt; 0.05). Native American patients who did not receive surgery were more likely to be older (62 vs 60 years old), have larger tumors, and have brain, bone, lung, and liver metastases (p &lt; 0.05). No associations of surgical versus non-surgical treatment were seen in Charlson-Deyo score, urban or rural residence, and primary payor at diagnosis. Conclusions: Native American patients with HCC who received surgical intervention experienced improved overall survival compared to non-surgical treatment groups. Native American patients undergoing surgical intervention more often received care at academic or private institutions and had lower stages of HCC. These results follow previous trends, where cancer patients receiving adequate surgical intervention generally survive longer. Further research is needed to examine other treatment differences among Native American patients and how these findings compare across other disadvantaged groups.

Discovery and Validation of a 15-Gene Prognostic Signature for Clear Cell Renal Cell Carcinoma.

Develop and validate gene expression-based biomarker associated with recurrent disease to facilitate risk stratification of clear cell renal cell carcinoma (ccRCC). We retrospectively identified 110 patients who underwent radical nephrectomy for ccRCC (discovery cohort). Patients who recurred were matched on the basis of grade/stage to patients without recurrence. Capture whole-transcriptome sequencing was performed on RNA isolated from archival tissue using the Illumina platform. We developed a gene-expression signature to predict recurrence-free survival/disease-free survival (DFS) using a 15-fold lasso and elastic-net regularized linear Cox model. We derived the 31-gene cell cycle progression (mxCCP) score using RNA-seq data for each patient. Kaplan-Meier (KM) curves and multivariable Cox proportional hazard testing were used to validate the independent prognostic impact of the gene-expression signature on DFS, disease-specific survival (DSS), and overall survival (OS) in two validation data sets (combined n = 761). After quality control, the discovery cohort comprised 50 patients with recurrence and 41 patients without, with a median follow-up of 26 and 36 months, respectively. We developed a 15-gene (15G) signature, which was independently associated with worse DFS and DSS (DFS: hazard ratio [HR], 11.08 [95% CI, 4.9 to 25.1]; DSS: HR, 9.67 [95% CI, 3.4 to 27.7]) in a multivariable model adjusting for clinicopathologic parameters (including stage, size, grade, and necrosis [SSIGN] score and Memorial Sloan Kettering Cancer Center nomogram) and mxCCP score. The 15G signature was also independently associated with worse DFS and DSS in both validation data sets (Validation A [n = 382], DFS: HR, 2.6 [95% CI, 1.6 to 4.3]; DSS: HR, 3 [95% CI, 1.4 to 6.1] and Validation B (n = 379), DFS: HR, 2.1 [95% CI, 1.2 to 3.6]; OS: HR, 3 [95% CI, 1.6 to 5.7]) adjusting for clinicopathologic variables and mxCCP score. We developed and validated a novel 15G prognostic signature to improve risk stratification of patients with ccRCC. Pending further validation, this signature has the potential to facilitate optimal treatment allocation.

Will coronal alignment postoperatively be deteriorating in adult spinal deformity after long-fusion surgery?

BackgroundTo investigate whether the coronal alignment (CA) will deteriorate, and identify the risk factors for coronal malalignment (CM) developing in adult spinal deformity (ASD) after long-fusion surgery.MethodsA multi-center retrospective study was performed, which included a total of 161 ASD patients who had undergone the surgical procedure of long-fusion (≥ 5 vertebras) with instrumentations in three medical centers. All of the participants were retrospectively reviewed, and subsequently assigned into the consistency group (C7 plumb line (C7PL) shifting towards the convex side of the main curve), and the opposition group (C7PL shifting towards the concave side). CM was considered if the coronal balance distance (CBD) being over 30 mm. A Kaplan–Meier curve and log-rank test were used to analyze the differences in CM-free survival during follow-up. Multivariate analysis via a Cox proportional hazards test was used to analyze the risk factors.ResultsPatients showing CM equaled 35 (21.7%) at the pre-operation, and that increased significantly up to 51 (31.7%) at the final follow-up (P = 0.04). In the consistency group, the incidence of CM at the final follow-up was much higher than that preoperatively (35:16, P = 0.002). CM-free survival time decreased significantly in patients with larger CBD correction, pelvic fixation and more instrumented segments, respectively, during follow-up (P < 0.05, log-rank test). Age ≥ 60 years, the consistency CA, pelvic fixation, CBD-correction ≥ 30 mm and fixed-vertebra ≥ 8 were risk factors for CM happening after surgery using multivariate regression analysis (P < 0.05).ConclusionsThe coronal alignments in ASD patients underwent long-fusion surgeries may deteriorate during follow-up, for which the risk factors include the consistency CA, age ≥ 60, fixed-vertebra ≥ 8, CBD-correction ≥ 30 mm and pelvic fixation.

Association between the ZJU index and risk of new-onset non-alcoholic fatty liver disease in non-obese participants: a Chinese longitudinal prospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) is increasingly observed in non-obese individuals. The ZJU (Zhejiang University) index has been established as a new and efficient tool for detecting NAFLD, but the relationship between the ZJU index and NAFLD within non-obese individuals still remains unclear. A post-hoc evaluation was undertaken using data from a health assessment database by the Wenzhou Medical Center. The participants were divided into four groups based on the quartile of the ZJU Index. Cox proportional hazards regression, Kaplan-Meier analysis and tests for linear trends were used to evaluate the relationship between the ZJU index and NAFLD incidence. Subgroup analysis was conducted to test the consistency of the correlation between ZJU and NAFLD in subsgroups. Receiver operative characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the ZJU index, compared with the Atherogenic index of plasma (AIP) and Remnant lipoprotein cholesterol (RLP-C) index. A total of 12,127 were included in this study, and 2,147 participants (17.7%) developed NAFLD in 5 years follow-up. Participants in higher ZJU quartiles tended to be female and have higher liver enzymes (including ALP, GGT, ALT, AST), GLU, TC, TG, LDL and higher NAFLD risk. Hazard Ratios (HR) and 95% confidence intervals (CI) for new-onset NAFLD in Q2, Q3, and Q4 were 3.67(2.43 to 5.55), 9.82(6.67 to 14.45), and 21.67(14.82 to 31.69) respectively in the fully adjusted model 3. With increased ZJU index, the cumulative new-onset NAFLD gradually increased. Significant linear associations were observed between the ZJU index and new-onset NAFLD (p for trend all<0.001). In the subgroup analysis, we noted a significant interaction in sex, with HRs of 3.27 (2.81, 3.80) in female and 2.41 (2.21, 2.63) in male (P for interaction<0.01). The ZJU index outperformed other indices with an area under the curve (AUC) of 0.823, followed by AIP (AUC=0.747) and RLP-C (AUC=0.668). The ZJU index emerges as a promising tool for predicting NAFLD risk in non-obese individuals, outperforming other existing parameters including AIP and RLP-C. This could potentially aid in early detection and intervention in this specific demographic.

Outcomes with enfortumab vedotin in patients with advanced urothelial carcinoma and histology variants: Analysis of the UNITE study.

652 Background: Enfortumab vedotin (EV) is approved for patients (pts) with advanced urothelial carcinoma (aUC) but outcomes in pts with histology variants (HV) have not been well described. We hypothesized that presence of HV would impact EV treatment outcomes. Methods: UNITE is a multi-site retrospective study of pts with aUC treated with targeted agents, including 650 pts treated with EV regimens. We compared outcomes to EV monotherapy in pts with pure UC (pUC) relative to pts with any HV and with specific HVs. In pts with scans after &gt; 1 cycle of EV, observed response rate (ORR) was assessed using χ2 test and logistic regression. Median progression-free survival (PFS) and overall survival (OS) from EV start were measured using the Kaplan Meier method and Cox proportional hazard test. Results: A total of 566 pts (366 with pUC; 200 with HV) from 17 US sites were treated with EV monotherapy. Median age was 70 years, 71% men, 87% Caucasian, 74% with ECOG PS 0/1 and 28% with liver mets. Median follow up was 21 mos from EV start, ORR was 49%, mPFS and mOS were 5.8 mos (95% CI: 5.29-6.67) and 12.2 mos (95% CI: 11.5 – 13.8), respectively. Pts with pUC had more visceral mets (69% vs 60%, p = 0.04) and liver mets (32% vs 21%, p =0.003) than pts with HV. No significant difference in outcomes were seen between pUC and pts with HV component (1-100%). Pts with predominant HV (50-99%; N=35), had numerically lower ORR relative to pUC pts (36% vs 52% OR 0.31, p &lt;0.09), but no difference in mPFS or mOS. Pts with pure HV (pHV) (100%: N=14) had inferior outcomes relative to pts with pUC (ORR 0% vs 52%, p&lt;0.001; mOS HR: 2.96 (95% CI: 1.60 – 5.46), p &lt;0.001; mPFS HR: 1.9 (95% CI: 1.06 – 3.39), p=0.03). ORRs for specific HV are listed in the table. No significant difference in treatment outcomes were seen in pts with pUC vs any specific HV, except for NE HV which had inferior ORR (0% vs 52%; p=0.003). Conclusions: Responses to EV are noted in some aUC pts with HV, except for NE (any component) and pHV. Certain HV notable for poor outcomes, such as sarcomatoid and plasmacytoid, demonstrated responses to EV. These hypothesis-generating findings require further validation in studies with adequate sample size for specific HV, and in particular pHV. Evaluation of biomarkers, including Nectin4 expression, in HV is paramount. [Table: see text]

Impact of squamous histology on outcomes with enfortumab vedotin in patients with advanced urothelial carcinoma: Analysis of the UNITE study.

651 Background: Squamous histology (SH) is the most common variant of Urothelial Carcinoma (UC) and is associated with lower response rates to chemotherapy. The impact of SH on outcomes with enfortumab vedotin (EV) is less defined. We hypothesized that increased SH component would correlate with inferior outcomes with EV treatment. Methods: UNITE is a multi-institutional retrospective study in pts advanced UC (aUC) treated with targeted agents. In this analysis, we compared EV monotherapy outcomes in pts with pure UC (pUC) and pts with urothelial predominant histology (UCP) [&lt;50% SH], SH-predominant [50-99% SH] and pure SH (pSH) [100% SH] respectively. We also compared pSH to UCP and SHP. Observed Response Rate (ORR) was compared in evaluable pts with scans after ≥1 cycle of EV using Chi-squared test. Progression-free survival (PFS) and overall survival (OS) from EV start were assessed and compared using the KM method and Cox proportional hazard test. Results: This analysis included 460 pts from 17 US sites treated with EV monotherapy. 366 pts had pUC and 94 pts had SH component (including pSH). In the overall cohort, median age was 70, 73% men, 88% Caucasian, 73% ECOG PS 0-1, 67% lower tract tumor, 30% liver mets, 38% bone mets, 65% had ≥ 2 prior therapy lines. There were no significant differences in baseline clinical characteristics between pts with pUC vs SH component except for higher incidence of liver mets in pts with pUC (32% vs 20%; p = 0.02). Among all 460 pts, median follow up was 20.7 mos from EV start, ORR was 51%, mPFS and mOS were 5.8 mos (95% CI: 5.3-6.4) and 12.7 mos (95% CI: 11.5-14.3). Among 94 pts with SH component, 70 were UCP, 17 SHP and 7 pSH. Inferior outcomes were noted in pts with pSH relative to pts with pUC and pts with UCP (Table). No differences in outcomes were seen across other cross-group comparisons. Conclusions: These hypothesis-generating findings suggest that SH component may impact outcomes with EV treatment in pts with aUC. A subset of pts with SH-predominant histology can have robust responses and outcomes with EV treatment, but larger studies and further biomarker data are needed to determine pts most likely to benefit. Patients with pSH are shown to have worse outcomes with EV, but further studies with a larger sample size are needed to validate our findings and define the role of EV for this rare and biologically distinct entity. [Table: see text]

Disparities in surgical outcomes and survival based on insurance status among patients with fibrolamellar hepatocellular carcinoma: A national perspective.

440 Background: Fibrolamellar hepatocellular carcinoma (FL-HCC), encompassing 1%-5% of all liver cancers, is a rare, malignant cancer that typically affects patients less than 40 years old. FL-HCC usually affects individuals with healthy livers and initially presents asymptomatically. Prior studies describe the importance of surgery on survival, with a 5-year survival of about 44%-68% with surgery versus 2%-17% without surgery. Disparities in outcomes regarding surgical factors and survival between private insurance, Medicare, Medicaid, and no insurance remain unknown. This study aims to determine differential surgical factors and survival of patients with FL-HCC based on insurance status. Methods: The National Cancer Database was used to identify patients diagnosed with FL-HCC from 2004-2019 using the histology code 8171 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, Chi-Square, ANOVA, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α=0.05. Results: Of the 436 patients included, 241 (55%) had private insurance and 96 (22%) had Medicare. Patients with private insurance had a longer median survival (49 months) than patients with Medicare (18 months; p&lt;.001) and Medicaid (26 months; p&lt;.004);no significant survival difference existed between Medicare, Medicaid, and no insurance (39 months) ( p’s≥.063). After controlling for age, income, tumor size, adjuvant therapy, receiving surgery, and surgical margins of primary site, private insurance was associated with an independent decrease in hazard (HR=.899; p=.004).Patients with private insurance received more surgery (68%) than those with Medicaid (50%), no insurance (48%), and Medicare (32%) ( p’s&lt;.001); grade did not differ amongst insurance types ( p=.069).Furthermore, patients with private insurance had more surgical margins of the primary tumor site without residual tumor (57%) compared to those with Medicaid (40%), no insurance (38%), and Medicare (23%) ( p’s&lt;.001).While patients with Medicare presented with greater co-morbidities, age at diagnosis (67), tumor size (476 mm), positive regional lymph nodes (90), and days between diagnosis and treatment (45), patients with private insurance presented at a younger age (31) with fewer co-morbidities, smaller sized tumors (366 mm), and fewer days between diagnosis and treatment (26) ( p’s&lt;.018). Conclusions: Since patients with private insurance received the most surgery, best surgical margins, and displayed the highest overall survival, while patients with Medicare were diagnosed at the highest age with the largest tumor size and most positive regional lymph nodes, future research should explore ways to alleviate the disparity in factors affecting surgical resections and early diagnoses among insurance statuses.

Evaluating local tumor destruction and wedge or segmental resection in the treatment of fibrolamellar hepatocellular carcinoma: An NCDB analysis.

512 Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare type of hepatic cancer, comprising 1% of all liver malignancies. Patients are often diagnosed in their second or third decade and often have a palpable liver mass. Treatment primarily consists of surgery and transplant, however, standardized protocols have not been well established due to its rarity. For patients who cannot receive a transplant, there are few studies examining and comparing other surgical types. Using the National Cancer Database, we aim to uncover survival and patient characteristic differences between those who receive Local Tumor Destruction vs Wedge or Segmental Resection. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with FL-HCC from 2004 to 2019 using the histology codes 8171 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α = 0.05. Results: Of the 803 patients in the sample,19 patients received Local Tumor Destruction (LTD) and 142 patients received Wedge or Segmental Resection (WSR). The average age of patients receiving LTD was 54 compared to 32 for WSR. WSR patients experienced longer overall survival than LTD (106 vs. 63 months respectively; p&lt;0.05). When controlling for age, year of diagnosis, tumor size, comorbidity score, and surgery type, WSR showed a greater decrease in overall hazard compared to LTD (HR=0.224 vs 0.306; p&lt;0.05). WSR use was highest in healthy patients with no co-morbidities, however, patients were also significantly more likely to have later stage tumors (II, III, and IV vs. stage I; p&lt;0.001). Despite being associated with a lower OS, LTD was utilized more commonly for earlier stage (stage I vs. II, III and IV; p&lt;0.001) and well differentiated tumors (p&lt;0.001). Compared to WSR, it was associated with higher rates of therapy before and after surgery(p&lt;0.05). There were no significant differences in tumor size, income group, adjuvant therapy type, or facility type (p&gt;0.05) between the treatment groups. Conclusions: Receipt of WSR is associated with improved survival compared to LTD. There are distinct demographic groups which may be guiding surgical selection. Further research into this disparity and other surgical types should be examined to create better guidelines for FL-HCC patients.

Patterns of surgery and adjuvant therapy in pancreatic carcinoid tumor: An NCDB analysis.

631 Background: Pancreatic Carcinoid Tumor (PCT) is a neuroendocrine tumor (NET) of the gastrointestinal (GI) tract composed of Argentaffin cells. Of the primary pancreatic cancers, NETs are exceedingly rare in comparison to pancreatic adenocarcinoma, accounting for less than 2% of pancreatic cancer diagnoses. PCTs constitute for only a subset of these and hold a better prognosis than adenocarcinoma (What Is a Pancreatic Neuroendocrine Tumor? | American Cancer Society, n.d.). GI carcinoid tumors classically originate in the appendix, ileum, or rectum, and are seldom a primary neoplasm of the pancreas. PCTs generate secretory products with Serotonin being the most frequently isolated. Some cases may produce a carcinoid syndrome with characteristic diarrhea, cutaneous flushing, and bronchospasm (Ha &amp; Tan, 2012). Surgical resection is the hallmark of treatment, though other modalities of management are available. Due to the rarity of PCT, no significant study exists in the literature analyzing the association of survival with receipt of surgery or predictors of receipt of surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PCT from 2004 to 2019 using the histology codes 8240 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, Binary Logistic Regression and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α = 0.05. Results: 2237 patients with PCT formed the final sample, with an average age of 61 years of age. 724 patients (32.3%) underwent surgery of the primary site, 72 (3.2%) received adjuvant chemotherapy, and 9 (0.4%) received adjuvant radiation. Surgery alone was associated with the longest median survival ( 198.5 months) compared to the other treatments ( Adjuvant chemotherapy=155.3 months, Adjuvant radiation=122.7 months, No surgery=73.95 months; p&lt;0.05). After controlling for covariates, receipt of surgery was independently associated with decreased overall mortality ( HR=.380; p&lt;0.05). Decreased age, lower grade tumors, and fewer positive regional lymph nodes were significantly associated with increased odds of receiving surgery. Additionally, treatment at an academic facility and private insurance status was associated with significantly higher rates of surgery. Patients who did not receive surgery were significantly older, had later stage disease, higher co-morbidity scores, and larger tumor size. Income level and race had no effect on treatment selection. Conclusions: This study found that surgery alone without adjuvant therapy is independently associated with improved survival. Favorable clinical characteristics may be contributing to this discrepancy in survival. Further exploration of treatment strategies in PCT may benefit patients through the creation of definitive treatment guidelines to manage this disease.

Clinical outcomes and impact of prognostic factors in resectable oral cavity squamous cell carcinoma.

To evaluate clinical outcomes and prognostic factors in non-metastatic oral cavity squamous cell carcinoma (OCSCC) patients who underwent surgery with or without adjuvant therapy. From 2007 and 2018, 116 patients were analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were disease-free survival (DFS), local failure (LF), regional failure (RF), and distant metastases (DM). Kaplan-Meier method and log-rank test assessed survival outcomes, while Cox proportional hazard tests analyzed prognostic factors. Median patient age was 53 years, most were smokers (93.5%) and males (62.9%). Predominant subsite was the oral tongue (58.6%). Treatment included surgery alone (16.4%), adjuvant radiotherapy (46.6%), or adjuvant concurrent chemoradiotherapy (CCRT) (37%). The median follow-up time was 45.9 months. There were significant differences between groups in terms of gender (P=0.028) and RT dose (P=0.01). The 3-year OS, DFS, LF, RF and DM for the entire cohort were 60.9%, 55.1%, 20.11%, 8.43%, and 17.13%, respectively. Surgery alone yielded higher 3-year OS (81.4%) than adjuvant RT (70%) or adjuvant CCRT (41.4%), (p=0.012). Adjuvant CCRT correlated with higher LF compared to adjuvant RT and surgery alone groups (p=0.029). Lymphovascular invasion (LVI) impacted OS (HR=2.034, p=0.0498) and DM (HR=3.380, p=0.0132), while higher tumor grade increased DM likelihood (HR=8.477, p=0.0379). This study reports OCSCC patient outcomes in Jordan across different treatment modalities. Adjuvant CCRT correlated with higher LF rates, and LVI impacted OS and DM, aligning with existing OCSCC treatment literature.

Overall survival differences in small intestine adenocarcinoma patients treated at academic vs non-academic facilities: A national perspective.

180 Background: Adenocarcinoma is a malignancy of glands lining organs in the human body. It is commonly found in the breast, lung, pancreas and throughout the digestive track. Prior research shows that common treatments include a combination of surgery, chemotherapy, and radiation. It also demonstrates that socioeconomic factors (such as income, insurance status, facility type) impact a patients’ survival. Thus, using the National Cancer Database (NCDB), this study aimed to evaluate the differential survival of patients treated at Academic or Non-Academic facilities for small intestine adenocarcinoma. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with small intestine adenocarcinoma from 2004 to 2019 using the histology code 8140 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: Of the 20,791 patients queried, 38% were treated at an academic/research facility (AF). Patients treated at an AF had an improved median survival compared to a non-academic facility (NA) (58 months versus 47 months; p &lt; 0.001). After controlling for income level, age, sex, race, adjuvant therapy and surgery, patients treated at an AF was associated with an independent decrease in hazard (HR=0.85, p&lt;0.001). AF patients disproportionately presented with a lower stage, had fewer lymph node metastases, had lower comorbidity scores, were more likely to receive chemotherapy, were more likely to receive surgery and come from a higher income bracket (p&lt;0.001). They were also more likely to have no residual tumor after surgery, have private insurance and receive palliative care (p&lt;0.001). There were no significant differences in grade/differentiation at presentation, 30-day surgical readmission rates, or phases of radiation treatment between patients treated at AF and NA. Conclusions: Patients treated at AF survived longer than patients treated at NA. While patients treated at AF were more likely to receive chemotherapy and surgery, controlling for those factors and others still resulted in a decreased hazard. It is a concerning finding that confirms prior research and underscores the need for further research to alleviate health care disparities.

Survival, Reintervention, and Value of Open and Endovascular Repair for Chronic Mesenteric Ischemia

There are limited analyses of survival and postoperative outcomes in chronic mesenteric ischemia (CMI) using data from large cohorts. Current guidelines recommend open repair (OR) for younger, healthier patients when long-term benefits outweigh increased perioperative risks or for poor endovascular repair (ER) candidates. This study investigates whether long-term survival, reintervention, and value differ between these treatment modalities. A retrospective cohort analysis was performed on data extracted from the Statewide Planning and Research Cooperative System, the New York statewide all-payer database containing demographics, diagnoses, treatments, and charges. Patients were selected for CMI and subsequent ER or OR using International Classification of Diseases, Ninth Revision codes. Patients with peripheral arterial disease were excluded to account for ambiguity in the International Classification of Diseases, Ninth Revision procedure code for angioplasty of noncoronary vessels, which includes angioplasty of upper and lower extremity vessels. Kaplan-Meier analysis was used to compare 1-year and 5-year survival and reintervention between treatment modalities using a propensity-matched cohort. Cox proportional hazards testing was performed to find factors associated with 1-year and 5-year survival and reintervention. Analysis of procedural value was performed using linear regression. From 2000 to 2014, 744 patients met inclusion criteria. Of these, 209 (28.1%) underwent OR and 535 (71.9%) ER. No difference between propensity-matched groups was found in 1-year (P=0.46) or 5-year (P=0.91) survival. Congestive heart failure (hazard ratio [HR]: 2.8, 95% confidence interval [CI]: 1.7-4.4; P<0.01), cancer (HR: 2.8, 95% CI: 1.3-5.8; P<0.01), and dysrhythmia (HR: 1.8, 95% CI: 1.1-2.8; P=0.02) correlated with 1-year mortality. Cancer (HR: 2.9, 95% CI: 1.6-5.5; P<0.01), congestive heart failure (HR: 2.2, 95% CI: 1.5-3.2; P<0.01), chronic pulmonary disease (HR: 1.4, 95% CI: 1.0-2.0; P=0.04), and age (HR: 1.03, 95% CI: 1.01-1.05; P<0.01) correlated with 5-year mortality. Treatment modality was not associated with reintervention at 1year on Kaplan-Meier analysis (P=0.29). However, ER showed increased instances of reintervention at 5years (P<0.01). Additionally, ER was associated with an increased 5-year value (0.7±0.9 vs. 0.5±0.5 life years/charges at index admission [$10k], P<0.01; b coefficient: 0.2, 95% CI: 0.1-0.4, P<0.01). This is the largest retrospective propensity-matched single-study cohort to analyze long-term survival outcomes after intervention for CMI. Long-term mortality was independent of treatment modality and rather was associated with patient comorbidities. Therefore, treatment selection should depend on anatomic considerations and long-term value. ER should be considered over OR in patients with amenable anatomy based on the superior procedural value.

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases

Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it is unknown whether ATM variants affect rates of radionecrosis (RN) and local intracranial progression (LIP) after stereotactic radiosurgery (SRS) for brain metastases. Patients undergoing an initial course of SRS for non-small cell lung cancer (NSCLC) brain metastases at a single institution were retrospectively identified. Kaplan-Meier estimates were calculated and Cox proportional hazards testing was performed based on ATM variant status. A total of 541 patients completed SRS for brain metastasis secondary to NSCLC, of whom 260 completed molecular profiling. Variants of ATM were identified in 36 cases (13.8%). Among patients who completed molecular profiling, RN incidence was 4.9% (95% CI, 1.6%-8.2%) at 6 months and 9.9% (95% CI, 4.8%-15.0%) at 12 months. Incidence of RN was not significantly increased among patients with ATM variants, with an RN incidence of 5.3% (95% CI, 0.0%-15.3%) at both 6 and 12 months (P=.46). For all patients who completed genomic profiling, LIP was 5.4% (95% CI, 2.4%-8.4%) at 6 months and 9.8% (5.5%-14.1%) at 12 months. A significant improvement in LIP was not detected among patients with ATM variants, with an LIP incidence of 3.1% (0.0%-9.1%) at both 6 and 12 months (P=.26). Although differences according to ATM variant type (pathologic variant or variant of unknown significance) did not reach significance, no patients with ATM pathologic variants experienced LIP. We did not detect significant associations between ATM variant status and RN or LIP after SRS for NSCLC brain metastases. The current data set allows estimation of patient cohort sizes needed to power future investigations to identify genetic variants that associate with significant differences in outcomes after SRS.

Introduction of E-Score: A gene expression score to characterize immunogenic versus oncogenic HPV expression in HNSCC.

6057 Background: Human Papillomavirus (HPV) integration in the human genome occurs in a majority of HPV(+) head and neck squamous cell carcinomas (HNSCC), with direct and indirect effects on host gene expression and tumorigenesis. Although previous studies showed that HPV integration in HNSCC is overrepresented in genes often somatically mutated in head and neck, lung, and urogenital cancers, reports are mixed for whether patients with HPV integration have worse clinical outcomes. These disparate results may be due to differences in how integration is defined. Integration can often lead to partial loss of the viral genome (e.g. HPV genes E1, E2, or E5) with retention of the oncogenes E6 and E7, which led to a low E2/E7 expression ratio being used as a biomarker for integration. Conversely, others have used the direct detection of DNA or RNA HPV-human breakpoints to identify tumors harboring integrated HPV. HPV integration and the retention or deletion of HPV genes can dramatically change the expression of HPV genes, and we hypothesize it also affects the host immune response. Hypothesis: Loss of non-oncogenic HPV genes relative to E6 and E7 levels reduces immunogenicity, leading to weakened immune cell infiltration and worse clinical outcomes. Methods: Bulk RNA sequencing data from HPV(+) HNSCC tumors (n = 136) was used to characterize the differences in retention or loss of HPV genes and calculate the E-Score as the sum of the logCPM of HPV genes E1, E2, E4, and E5 relative to E7. Cell type deconvolution was performed using ComBat to correct for batch effects, and CIBERSORTx to quantify cell type proportions within the tumor samples. Kaplan-Meier estimates of recurrence and overall survival (OS) were calculated, and Cox proportional hazards tests with covariates were used to test for association with recurrence and OS. To test the correlation between immune cell type inferred proportions and E-Score, T-Tests were performed between samples with high and low E-scores. Results: Low E-Score was significantly associated with recurrence (p = 0.012) but not with OS (p = 0.39) in the multivariate model accounting for age, tumor stage (AJCC8), smoking status, drinking status, BMI, marital status, and molecular tumor subtype (defined as IMU or KRT). For integration positive samples (n = 66), higher E-Score, suggesting lower rates of HPV gene loss, was correlated with higher percentages of dendritic cells (p = 0.044), macrophages (p = 0.021), and CD8+ T Cells (p = 0.024), but not CD4+ T cells (p = 0.14). This significance did not hold when looking at integration negative samples. Conclusions: These results suggest that HPV+ HNSCC patients with a loss of E1, E2, E4 and E5 tend to have less immune cell infiltration and are more likely to have recurrence. We conclude that E-Score is a potential prognostic biomarker of recurrence in HPV+ HNSCC and potential predictive biomarker for immunotherapy.