Significant Difference In Median Survival Research Articles

The Prognostic Impact of Plasma Cell Chromosome 17 Abnormality Percentage Cut-offs on Patient Outcomes in Multiple Myeloma

Abstract Abnormalities in chromosome 17 encompassing the TP53 locus [deletion of the small arm {del (17p)} and monosomy 17] as identified by fluorescent in-situ hybridization (FISH), are a well-established adverse prognostic factor in multiple myeloma (MM). Previous research suggested that higher percentages of these chromosome 17 abnormalities correlate with worse prognoses, proposing various cutoff points to assess this relationship, ranging between 50-60%. Of note, these studies employed extensive plasma cell enrichment protocols and often included only cases with high plasma cell percentages (70-90%). Our study aims to investigate the relationship between the percentage of plasma cells with chromosome 17 abnormalities and patient outcomes at the time of acquisition of the abnormality, scrutinizing various cut-off points for prognostic significance. We retrospectively reviewed 339 MM patients at our institution, including newly diagnosed and relapsed cases, examining chromosome 17 abnormality levels identified by FISH on bone marrow specimens. After CD138 magnetic bead enrichment, 50 nuclei were scored for these abnormalities and the percentage calculated. It is important to note that the precise percentage of plasma cells in the sample was not quantified. We analyzed survival outcomes across different percentage cut-off points (20%, 40%, 50%, 55%, 60%, and 80%) using Kaplan Meier analysis and log-rank tests. Significant differences in median survival were noted at the 40% and 50% cut-offs. Patients with >40% chromosome 17 abnormalities showed a median survival of 17.5 months compared to 25.8 months for those with ≤40% (p<0.05), an absolute difference of 8.3 months. Similarly, the >50% group had a median survival of 19.4 months versus 24.3 months in the ≤50% group (p<0.05), with an absolute difference of 4.9 months. However, these differences, while statistically significant, may not be clinically substantial. Furthermore, a 55% cut-off did not yield a significant survival difference (23.5 months vs. 19.8 months for ≤55% and >55% groups, p>0.05) in our cohort. Our findings confirm some prognostic value of chromosome 17 abnormality levels in MM but suggest that the absolute differences in median survival at certain cut-offs, based on the test as performed in our laboratory, might not be clinically impactful. This may be due to differences in the proportion of non-plasma cells within the samples being scored, resulting in ambiguity when interpreting FISH results. Future research should aim to improve the consistency of plasma cell enrichment, develop approaches to score only plasma cells, establish risk-specific cut-offs, and explore the relationship between chromosome 17 abnormality levels, treatment response, and overall significance. The study raises important questions about the necessity of stratifying patients based on chromosome 17 abnormality levels versus simply detecting their presence for prognostic assessment.

The effect of tumor laterality on prognosis in metastatic renal cell carcinoma

Aim: In metastatic renal cell carcinoma (RCC), prognosis relies on various factors. Tumor lateralization's role is still debated. Our study examined how tumor localization affects survival in metastatic RCC patients.Materials and Methods: The study retrospectively analyzed 80 patients with metastatic renal cell carcinoma, diagnosed between January 1999 and December 2021. Results: Eighty patients were evaluated. The median age at diagnosis was 60 (range 37-86). Tumors were in the right kidney for 39 patients (48.8%) and in the left kidney for 41 patients (51.2%). Of these patients, 58 (72.5%) had de novo metastatic disease, while 22 (27.5%) had recurrences during follow-up. Tumor localization showed no significant association with age (p=0.684), gender (p=0.761), ECOG performance status (p=0.326), primary tumor surgery (p=0.697), or lung metastasis (p=0.495). However, a significant association was found with liver metastasis (p=0.032). There was no significant difference in median survival between right and left-sided tumors (p=0.266). Conclusion: In our study, survival showed no correlation with tumor lateralization in metastatic RCC.

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

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

Radiotherapy protocol compliance in routine clinical practice for patients with stages I-III non-small-cell lung cancer.

Despite the availability of radiotherapy treatment protocols forlung cancer, considerable treatment variation occurs in clinical practice. This study assessed compliance with a radiotherapy protocol for the treatment of patients with stages I-III non-small-cell lung cancer (NSCLC) in routine clinical practice and to identify factors that were associated with compliance. The Cancer Institute New South Wales eviQ treatment protocol for external beam radiotherapy of stages I-III NSCLC was taken as the reference to measure compliance. All inoperable patients with stages I-III NSCLC and documented ECOG performance status treated with radiotherapy between 2007 and 2019 at two radiotherapy facilities were available for analysis. Protocol compliance rates were calculated. Univariate and multivariate logistic regression models with 23 input factors were used to determine factors significantly associated with compliance. Survival analysis was conducted for both compliant and non-compliant treatments. Overall, 656 patients met the inclusion criteria. Protocol compliance was 16%. Alternative dose/fractionation was responsible for 49% of non-compliant treatments with 30% receiving an alternative curative fractionation. Five of 23 factors (age at the start of radiotherapy, stage group, ECOG performance status, tumour location and alcoholism history) showed significant associations with protocol compliance on multivariate analysis. There was no significant difference in median survival between patients receiving protocol compliant treatment (15.1 months) and non-compliant treatment (15.6 months). Adherence to the eviQ curative radiotherapy protocol for stages I-III NSCLC was low. Alternative dose/fractionation schemes were the main reason for non-compliance. Protocol compliance was not associated with outcome.

Association of proteinuria at time of diagnosis with survival times in dogs with lymphoma.

Lymphoma has been implicated as a possible cause of proteinuria in dogs. However, information about the potential importance of proteinuria in dogs with lymphoma is limited. To determine if the presence of proteinuria at diagnosis was associated with median survival times in dogs with lymphoma and if lymphoma stage (I-V) or type (B vs T) were associated with the presence of proteinuria. Eighty-six client-owned dogs with a new diagnosis of lymphoma between 2008 and 2020. This was a retrospective cross-sectional study with dogs divided into proteinuric or nonproteinuric groups based on dipstick urine protein (protein ≥30 mg/dL classified as proteinuric) or a ratio of dipstick protein to urine specific gravity (ratio ≥1.5 classified as proteinuric). Dogs were excluded for: (1) treatment within 2 months with glucocorticoid, anti-neoplastic, or anti-proteinuric therapies, (2) diagnosed hypercortisolism or renal lymphoma, (3) active urine sediment, or (4) urine pH >8. Survival analysis utilized a Kaplan-Meier estimator and log-rank testing. There was a significant difference in median survival between proteinuric and nonproteinuric dogs classified by urine dipstick (245 days [91, 399] vs 335 days [214, 456]; P = .03) or UP : USG (237 days [158, 306] vs 304 days [173, 434]; P = .03). No difference in prevalence of proteinuria was identified between stages (I-V) or types (B and T). Proteinuria appears to be negatively associated with survival time in dogs newly diagnosed with lymphoma.

A multicentric outbreak of Candida auris in Mexico: 2020 to 2023

Candida auris, an emerging multidrug-resistant yeast, has become a global concern due to its association with nosocomial outbreaks and resistance to antifungal medications. The COVID-19 pandemic has exacerbated the situation, with several outbreaks reported worldwide, including in Mexico. We describe the clinical and microbiological characteristics of a multicentric outbreak in private institutions in Mexico. A retrospective observational study was conducted across 4 Christus Muguerza Hospital Health Care System facilities in Monterrey, Mexico, where simultaneous outbreaks of C auris occurred. Patients with colonization or infection with C auris between September 2020 and December 2023 were included. Analysis revealed 37 cases, predominantly male (median age, 55.8years). While most cases were initially colonization, a significant proportion progressed to infection (32.4%). Patients with documented infection had longer intensive care unit and hospital stays, often requiring mechanical ventilation. Antifungal treatment varied, with empirical fluconazole being the first drug in most cases, followed by anidulafungin and caspofungin. Resistance to fluconazole was widespread, but susceptibility to other antifungals varied. The overall mortality rates were high (40.5%), with no significant difference in median survival between colonized and infected patients. We reported a high rate of infection in previously colonized cases associated with longer hospital lenght stay, and a high susceptibility to echinocandins.

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

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

Repetitive nerve stimulation on survival in amyotrophic lateral sclerosis.

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

Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics?

Triple negative breast cancer (TNBC) is a breast carcinoma subtype that neither expresses estrogen (ER) and progesterone receptors (PR) nor the human epidermal growth factor receptor 2 (HER2). Patients with TNBC have been shown to have poorer outcomes mainly owing to the limited treatment options available. However, some studies have shown TNBC tumors expressing androgen receptors (AR), raising hopes of its prognostic role. This retrospective study investigated the expression of AR in TNBC and its relationship with known patient demographics, tumor and survival characteristics. From the records of 205 TNBC patients, 36 had available archived tissue samples eligible for AR staining. For statistical purposes, tumors were classified as either "positive" or "negative" for AR expression. The nuclear expression of AR was scored by measuring the percentage of stained tumor cells and its staining intensity. AR was expressed by 50% of the tissue samples in our TNBC cohort. The relationship between AR status with age at the time of TNBC diagnosis was statistically significant, with all AR positive TNBC patients being greater than 50 years old (vs 72.2% in AR negative TNBC). Also, the relationship between AR status and type of surgery received was statistically significant. There were no statistically significant associations between AR status with other tumor characteristics including "TNM status", tumor grade or treatments received. There was no statistically significant difference in median survival between AR negative and AR positive TNBC patients (3.5 vs 3.1 years; p = 0.581). The relationship between OS time and AR status (p = 0.581), type of surgery (p = 0.061) and treatments (p = 0.917) were not statistically significant. The androgen receptor may be an important prognostic marker in TNBC, with further research warranted. This research may benefit future studies investigating receptor-targeted therapies in TNBC.

PD17-04 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY WITH IMMUNE CHECKPOINT INHIBITOR THERAPIES IN METASTATIC RENAL CELL CARCINOMA MURINE MODEL

You have accessJournal of UrologyCME1 Apr 2023PD17-04 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY WITH IMMUNE CHECKPOINT INHIBITOR THERAPIES IN METASTATIC RENAL CELL CARCINOMA MURINE MODEL Jee Soo Park, Myung Eun Lee, Won Sik Jang, Jongchan Kim, Se Mi Park, and Won Sik Ham Jee Soo ParkJee Soo Park More articles by this author , Myung Eun LeeMyung Eun Lee More articles by this author , Won Sik JangWon Sik Jang More articles by this author , Jongchan KimJongchan Kim More articles by this author , Se Mi ParkSe Mi Park More articles by this author , and Won Sik HamWon Sik Ham More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since CARMENA trial found non-inferiority of sunitinib alone, the contemporary role of cytoreductive nephrectomy (CN) has been significantly downsized. However, updated CARMENA trial results demonstrated certain subsets with metastatic renal cell carcinoma (mRCC) may still benefit from CN. We tried to assess the role of CN in combination with immune checkpoint inhibitor (ICI) from the perspective tumor immune microenvironment (TIME). METHODS: Low- and high-tumor burden pulmonary metastatic orthotopic murine mRCC models have been developed. Anti-PD-1 and anti-CTLA-4 antibodies were systemically injected through the peritoneum every 3 days. Renca implanted kidney was removed in the CN performed group. For the upfront CN plus ICI group, CN was performed 1 day before the ICI, while CN was performed 5 days after ICI for the deferred CN plus ICI group. The remodeling of the TIME was determined using immunofluorescence analysis. RESULTS: Low- and high-tumor burden murine mRCC models have been successfully developed with statistically significant difference in median survival (p<0.05). In low-tumor burden model (Figure 1A), upfront CN plus ICI group demonstrated significantly better survival outcomes compared to deferred CN plus ICI group. In high-tumor burden model (Figure 1B), similar results were shown as low-tumor burden model, except no significant survival difference between ICI only and CN only group, and between upfront CN plus ICI and deferred CN plus ICI group. Immunofluorescence analysis demonstrated that CN modulate TIME by increasing M1 tumor-associated macrophage (TAM) and at the same time decreasing M2 TAM (Figure 2). CONCLUSIONS: This study is the first animal study to demonstrate the role of CN in combination with ICI. We have shown that the CN has certain role in the immune-oncology (IO) era and was associated with improved survival by the regulation of M1 and M2 TAM. CN also regulated myeloid-derived suppressor cells and regulatory T cells in combination with ICIs although not to be significant in our study. Source of Funding: This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI17C1095], and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [grant number: 2019R1A2C1002863 and 2022R1A2C2003831] © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e496 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jee Soo Park More articles by this author Myung Eun Lee More articles by this author Won Sik Jang More articles by this author Jongchan Kim More articles by this author Se Mi Park More articles by this author Won Sik Ham More articles by this author Expand All Advertisement PDF downloadLoading ...

Atypical teratoid rhabdoid tumours (ATRTs)-a 21-year institutional experience.

Atypical teratoid/rhabdoid tumours (ATRTs) are malignant embryonal tumours of childhood that affect the central nervous system (CNS). We aim to determine which factors, including patient age, extent of resection (EOR), presence of distal metastasis and use of adjuvant therapies, affect overall survival in children with atypical teratoid/rhabdoid tumours (ATRTs) treated at this single centre. Retrospective cohort review of patients with histological diagnosis of ATRT treated over 21years (1999-2020) was conducted. Data on demographics, tumour location, presence of metastasis, use of adjuvant therapy, extent of resection (EOR), complications, neurological outcome post-surgery, and overall survival were collected. Kaplan-Meier survival analysis was performed. A total of 45 children (mean age 2 years) underwent 64 operations. 25 patients were <1year of age. Gross-total resection (GTR) pre-adjuvant therapy was achieved in 15, near-total resection (NTR) in 15, subtotal resection (STR) in 9, and biopsy in 6 children. Most children had good neurological outcomes post-operatively (28/45 with GOS 5). Fourteen patients survived longer than 4 years. Survival analysis showed a significant difference in median survival in favour of GTR and localised disease. There was no significant difference in median survival between patients <1year vs >1year of age (p=0.84). We find that presence of metastasis was an important factor in poor survival inpatients with ATRT. GTR, where possible, may confer significant survival benefit in ATRT. Children aged <1year appear to have performed as well as those >1year and therefore should stillbe considered for radical surgery.

Early post-bevacizumab change in rCBV from DSC-MRI identifies pseudoresponse in recurrent glioblastoma: Results from ACRIN 6677/RTOG 0625.

Progressive enhancement predicted poor survival in ACRIN 6677/RTOG 0625, a multi-center trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma, but pseudoresponse likely limited enhancement-based survival prognostication in T1 non-progressors. We aimed to determine whether early change in cerebral blood volume from baseline (ΔCBV) could further stratify the T1 non-progressors according to overall (OS) and progression-free (PFS) survival. 37/123 enrolled patients had DSC-MRI, including 13, 15, and 8 patients without 2D-T1 progression at 2, 8, and 16 weeks post-treatment initiation, respectively. Mean CBV normalized to white matter (nRCBV) and mean standardized CBV (sRCBV) were extracted from enhancing tumor. ROC curves were derived for ΔCBV using six-month PFS and one-year OS as reference standards. Kaplan-Meier survival estimates and log-rank test compared PFS and OS for both ΔCBV (increase vs. decrease) and T1 response status (stable vs. decreasing enhancement). PFS and OS were significantly worse for increasing CBV at 2 weeks (p=0.003 and p=0.002 for nRCBV, and p=0.03 and p=0.03 for sRCBV, respectively), but not for 2D-T1 patients with stable vs. decreasing enhancement (p=0.44 and p=0.86, respectively). ΔCBV at week 2 was also a good prognostic marker for OS-1 and PFS-6 using ROC analysis. By contrast, 2D-T1 response status at weeks 2, 8, and 16 was not associated with PFS-6. ΔCBV at 16 weeks (p=0.008 for sRCBV) but not 8 weeks (p=0.74 for nRCBV and p=0.56 for sRCBV) was associated with significant difference in median survival, but no difference in survival was observed for 2D-T1 patients with stable vs. decreasing enhancement at 8 weeks (p=0.69) or 16 weeks (p=0.21). At 16 weeks, OS did not differ significantly between 2D-T1 progressors and 2D-T1 non-progressors with increasing CBV (median survival 3.3 months post week 16 scan vs. 9.2 months, respectively; p=0.13), suggesting that 2D-T1 non-progressors with increasing CBV may have a prognosis like that of 2D-T1 progressors. After 2 weeks of anti-angiogenic therapy, ΔCBV in 2D-T1 non-progressors significantly prognosticated PFS and OS, whereas 2D-T1 response status did not, identifying a subpopulation that benefits from bevacizumab. Combining 2D-T1 progression and ΔCBV may yield a response assessment paradigm with 3-tiered OS stratification.

Current Status of Racial and Ethnic Disparities for Follicular Lymphoma: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis with Emphasis on Hispanics

Background Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the Western hemisphere (Blood PMID: 26989204). In prior studies, better progression-free survival has been noted in Hispanics (HI), however, further characterization of this ethnic difference needs to be addressed. This result is consistent with previous research explaining the development of NHL as an heterogeneous process where unique outcomes for races have been noted. There is a need for further understanding of HI diagnosed with FL. METHODS: Data were analyzed on follicular FL patients in the United States (US) reported to the Surveillance, Epidemiology, and End Results (SEER) 18 database between 2000 and 2018. SEER 18 contains the most comprehensive population-based cancer information in the US, covering approximately 27% of the total US population, and up to 36% of HI alone. Racial groups analyzed included NH whites, HI whites, blacks, and Asians/PIs (Pacific Islanders). Patient characteristics, age-adjusted incidence rate, and survival rate were compared across ethnic groups, HI vs NH. Stratification by age, gender, and stage at diagnosis was considered. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between HI and NH. Multivariate analysis and propensity score matching were performed with adjustment for age, stage and B-symptoms. RESULTS Of 59250 FL patients, 11% were HI, and 89% NH. 48% of HI were male, compared to 50% of NH. The majority of HI (42%) were diagnosed in the age bracket of (40-60) vs majority of NH (50%) who were diagnosed in the age bracket of (60-80) (p<0.001). HI were diagnosed at a median younger age, 59 y.o vs 65 y.o, compared to NH (p<0.001). Regarding race, most of HI and NH were whites (96% vs 88%), followed by blacks (1% vs 5%). When examining stage, most of HI (22%) as well as NH (22%) were stage IV (p<0.001). In terms of radiation, 13% of HI received it, compared to 14% of NH (p<0.001). On survival analysis, the survival probability at 2, 5 and 10 years of HI vs NH were (87%vs 86%),(77% vs 74%), and (64% vs 86%), respectively. The median survival time was 17.1 years for HI, vs 13.2 years for NH; and there was OS difference favoring HI/NH with (p<0.001). On multivariate analysis, when adjusted for age, those patients who were older than 80 y.o and between 60 to 80 y.o, had worse OS compared to those younger than 60 y.o, with hazard ratio (HR) 9.4 (95% CI: 8.7 - 10 ) and HR 3 (95% CI: 2.8-3.2) respectively. Regarding stage, those who were at stage III and IV, had worse OS than those at early stage (I/II) with HR 1.3 (95% CI: 1.26 - 1.45) and HR 1.7 (95% CI: 1.6 - 1.8), respectively. CONCLUSION In this data analysis from the SEER 18 database, HI with FL lymphoma, had a statistically significant prolonged OS compared to NH. There were also, statistically significant differences in median survival at 2, 5, and 10 years among the HI cohorts. Unique characteristics from HI may explain why there is an increase in OS after a FL diagnosis in this data set. Biological differences in the background of HI with FL are needed to better understand improved outcomes on this cohort. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Brain metastasis from colorectal cancer: Treatment, survival, and prognosis.

To investigate the clinical characteristics, survival, prognostic factors, and treatment of brain metastasis (BM) from colorectal cancer (CRC). Twenty-one patients with BM from CRC were retrospectively reviewed. Predictive factors for BM and prognostic factors after the diagnosis of BM were examined by univariate and multivariate COX analysis. The time from the development of extracranial metastases, including lung, bone, and liver, to the occurrence of BM was recorded separately. The median overall survival time was 7 months. In univariate prognostic analysis, median survival with multimodal therapy was better than that with unimodal therapy (10 months vs 3 months, P = .000). In addition, median survival with Karnofsky performance status (KPS) < 70, 1 BM lesion, primary tumor stage of II-III, extracranial lesions < 2, and no extracranial metastasis were much better than the other groups (P < .05 of all). Although there was not a significant difference in median survival between patients receiving combination treatment with bevacizumab and those who did not, treatment with bevacizumab was associated with better survival (10 months vs 5 months, P = .436). The time intervals from bone, liver, and lung metastases to BM were 3, 6.5, and 11 months, respectively. Based on multivariate Cox analysis, KPS and treatment modalities were independent prognosis factors (P = .039 and P = .000, respectively). CRC patients with a high KPS and multimodal treatment have improved survival.

Survival trends in hilar and extrahepatic cholangiocarcinoma based on Facility type: A National Cancer Database analysis.

e13536 Background: The diagnosis and treatment of Cholangiocarcinoma continues to pose a challenge. Due to their rarity, few studies have examined the impact of facility type on the survival of patients with extrahepatic cholangiocarcinoma. The hypothesis of this study was that differences in the outcome of patients at different facility types exist. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with hilar and extra-hepatic cholangiocarcinoma from 2004 to 2017 using ICD-O-3 histology codes. We used four different cohorts to assess survival amongst those at different facility types: academic/research programs, community cancer programs, comprehensive community center programs, and integrated network cancer programs. Data was analyzed and descriptive statistics and Kaplan Meier curves were produced using SPSS to measure survival in these patients with statistical significance set at α = 0.05. Results: Using the database, a total of 57,146 patients with hilar and extrahepatic cholangiocarcinoma were identified. Overall median survival in these patients was 11.2 months. Patients at Academic/research programs had a median survival of 14 months (95% CI 14.1-14.8 p &lt; 0.001). In comparison, median survival of 9.7 months (95%CI 9.3-10.2 p &lt; 0.001) and 8.7 months (95% CI 8.4-8.9 p &lt; 0.001) was noted in Integrated network and Comprehensive community cancer programs, respectively. Community cancer programs had the lowest median survival rate in patients with all extrahepatic biliary tract cancers included in our study was 6.9 months (95% CI 6.4-7.7 p &lt; 0.001). Specifically, patients with Klatskin tumors at Academic/Research programs had median survival of 10.3 months (95% CI 8.6-11.9 p &lt; 0.0010) compared to median survival of 3.6 months in patients treated at Community Cancer program. We also studied specific histology types such as papillary and mucinous adenocarcinomas. In papillary adenocarcinomas, there are no statistically significant differences in median survival in different facility types. In mucinous adenocarcinomas, median survival of 26.5 months was found in academic/research program patients compared to 16.2 months in Comprehensive Community Cancer program patients (p &lt; 0.001). Conclusions: Median overall survival in patients with hilar and extrahepatic cholangiocarcinoma was significantly higher in academic/research programs compared to other facility types. Further studies are needed to ascertain why academic/research programs have superior outcomes in these patients.

Treatment outcomes of patients with metastatic prostate cancer and co-morbid diabetes mellitus.

113 Background: In metastatic castrate resistant prostate cancer (mCRPC) there is a lack of studies that explore the interaction of comorbidities on treatment outcomes, which presents a challenge in choosing the right drug. In patients with diabetes mellitus, two common therapies, enzalutamide (ENZ) and abiraterone (ABI) have different effectiveness due to different mechanisms of action and because ABI requires co-administration of prednisone. Thus, in this study, we aim to assess the survival of patients with comorbid diabetes treated with ENZ and ABI. Methods: Patients treated with AA or ENZ for mCRPC from September 10, 2014, to June 2, 2017 were identified within the Veterans Health Administration. For these patients, presence of diabetes or complicated diabetes was determined using the Charlson method from the International Classification of Diseases (ICD) 9/10 codes. A Kaplan–Meier time to event analysis and the cox proportional hazards modeling was used to analyze the data with the latter including covariates such as age, Charlson Comorbidity Index, body-mass index, treatment with bone-directed therapy, black race, and baseline PSA at start of treatment with ENZ or ABI. Results: We identified 5822 patients treated for mCRPC, of which 2202 had diabetes and were treated using either ENZ (n = 1041) or ABI (n = 1161). Median survival of patients with diabetes treated with ENZ was 3 months longer than in patients treated with ABI (23.8 vs. 20.8, p = 0.002 by log-rank). In 3620 patients without diabetes, no significant difference in median survival (24.7 vs. 22.7 months, p = 0.065) was seen between ENZ (n = 1463) and ABI (n = 2157). In a multivariable model, ENZ was associated with improved survival in patients with diabetes (adjusted HR 0.87, 95% CI 0.79-0.97) and in patients without diabetes (adjusted HR 0.90, 95% CI 0.83-0.98). Conclusions: ENZ was associated with improved 3-month median survival in patients with diabetes compared to ABI in unadjusted analyses. Additionally, in adjusted analyses the cox proportional model also showed significantly better survival in mCRPC patients treated with ENZ both with and without diabetes, although the findings are more robust for patients with diabetes. The cause of these differences is unknown, so there may be differences in efficacy and adverse events between the two agents in real-world use. Further assessment of patient outcomes with comorbid disease is appropriate to improve care of patients with advanced prostate cancer.

POS-732 QUALITY OF LIFE AND ONE-YEAR SURVIVAL OF PATIENTS WITH KIDNEY FAILURE IN A RESOURCE LIMITED SETTING

In 2017, 1.2million people died due to kidney failure making it the 12th leading cause of death globally. This position has risen from 17th over the past three decades. The global burden of kidney failure is most felt in Resource Limited Settings (RLS) such as Uganda in Sub-Saharan Africa (SSA). In most of SSA, patients never receive renal replacement therapy due to limited accessibility or proximity to these services and of those initiated onto dialysis, 85% will discontinue it due to cost limitations to maintain healthcare expenditure thus leading to premature death. The objective of this study was to determine the survival and changes in Quality of Life (QOL) of kidney failure patients receiving care in a tertiary hospital in Uganda over a one-year period. Patients aged ≥18 years with kidney failure were recruited from the renal outpatients’ clinic, hemodialysis unit and inpatient ward of tertiary hospital in Uganda, and followed up for 12months. Survival rates were calculated using the Kaplan Meier method and factors associated with survival analysed with the log rank test. Quality of life was calculated using the Kidney Disease and Quality of Life-Short Form (KDQOL-SF™) version 1.3 questionnaire. Scores less than 50 were considered to be indicative of poor QOL. Data was analysed for 335 patients recruited into the study. 216 (64%) patients were on Conservative Management (CM) while 119 (34%) were on Hemodialysis (HD). Overall, one-year survival was 26.6%; 95%CI (21.8 – 31.2). There was no statistically significant difference in median survival of patients on CM (7.6 months) in comparison to those on HD (8 months) (p-value 0.3984). Male sex and distance from the hospital were significantly associated with shorter survival HR 1.38 (CI 1.04-1.83) while belonging to a protestant faith improved survival HR 0.64 (CI 0.48-0.88). Quality of life scores changed significantly for 13 out of 19 subdomains of the KDQOL-SF™. Subdomain scores that changed the most included- Social support; 75.6 ±29.2 at baseline to 27.7 ±19.4 at one year (p-value <0.001), and Effects of kidney disease 54± 20 to 70± 23 (p-value <0.001). All three composite summary scores; -mental health, physical health and kidney disease specific, showed statistically significant increases but remained less than 50 throughout the one-year follow up. Survival is dismal for patients with kidney failure with no survival or QOL advantage offered by HD in comparison to CM in this setting. Male sex and residence far from the hospital were associated with reduced survival and protestant faith improved survival despite poor QOL scores and a marked decline in social support over the one-year period. To improve patient outcomes in RLS, health systems need to increase accessibility and affordability of specialist renal services including; trained human resources and renal replacement therapy options, as well as integrate spiritual support, financial literacy and social support services into existing care practices.

Long-term outcomes and interventions of postoperative type 1a endoleak following elective endovascular aortic aneurysm repair.

This study evaluated the incidence and long-term outcomes of postoperative type 1a endoleak (PT1a) following endovascular aortic aneurysm repair (EVAR). A retrospective review of consecutive aortoiliac EVARs performed at a single institution from June 2006 to June 2012 was conducted. Patients with PT1a were identified by postoperative imaging and compared with those who did not develop a PT1a. Late outcomes were also studied of a subset of patients with PT1a who had persistent intraoperative type 1a endoleak (iT1a) on completion angiogram during EVAR that had resolved on initial follow-up imaging. Three hundred eighty-nine patients underwent EVAR with median follow-up of 87months (interquartile range, 64-111months). The incidence of PT1a was 8.2% (n= 32) with a median follow-up of 74months (interquartile range, 52-138months). Compared with the total cohort, those who developed PT1a were statistically more likely to be female (32% vs 17%; P= .03) and have a higher all-cause mortality (71% vs 40%; P< .01) and aneurysm-related mortality (15.6% vs 1.7%; P< .01). Median time to presentation was 52months. Of the 32 patients with PT1a, five (15.6%) presented with aortic rupture, of which three underwent extension cuff placement, one had open graft explant, and one declined intervention. Six patients in total (18.7%) declined intervention; five of these died of nonaneurysmal causes and one remains alive. Of the 26 patients with PT1a who had intervention, 21 (80.7%) showed resolution of PT1a, and five (19.2%) had recurrence. For patients with recurrent PT1a, two had resulting aneurysm-related mortality, two endoleaks resolved after relining with an endograft, and one patient declined intervention but remains alive. Patients with PT1a who had intervention with resolution showed no significant difference in median survival estimates (140.0months) compared with the remaining EVAR cohort (120.0months; P= .80). Within the PT1a cohort, 6 (18.7%) had also experienced iT1a with a mean time to presentation of the late PT1a of 45months. iT1a was associated with a significantly increased likelihood of developing a PT1a (P< .01) and decreased median survival (P< .01), but there was no known aneurysm-related mortality. Development of PT1a following elective EVAR is associated with increased all-cause and aneurysm-related mortality and presents an average of 52months postoperatively. This underscores the importance of long-term surveillance. Patients with PT1a who had a successful intervention showed no significant difference in median survival. Those with iT1a had a higher risk for PT1a compared with the EVAR cohort overall and had decreased median survival, without increased aneurysm-related mortality.

Post-chemotherapy Changes in Bone Marrow in Acute Leukemia With Emphasis on Detection of Residual Disease by Immunohistochemistry.

IntroductionIn acute leukemia, the leading cause of treatment failure is disease relapse leading to a low level of complete remission and short overall survival. Post-chemotherapy marrow examination gives vital clues regarding treatment response and marrow regeneration.AimWe aimed to study the histomorphological changes in post-chemotherapy bone marrow in acute leukemias, monitor residual disease by immunohistochemistry (IHC) on trephine biopsy, and correlate survival status.MethodThis study was a prospective clinical study. A total of 155 post-induction cases (acute myeloid leukemia [AML] - 68 and acute lymphoblastic leukemia [ALL] - 87), from January 2014 to December 2015, were included with a follow-up of 4-28 months. A detailed histomorphology was studied in all cases. IHC was applied in 88 cases of post-induction marrow, which showed morphologic suspicion of an increase in blasts.ObservationsPost-induction marrow was hypercellular in 55.9% of AML and normocellular in 56.3% of ALL. Regenerative hematopoiesis was noted in 37.4% of AML and 88.5% of cases of ALL. Marrow serous atrophy and stromal edema were associated with delayed recovery of counts and their recovery duration ranged from one to five months. Twenty-seven bone marrow aspirates were unsatisfactory, and their trephine biopsies were showed remission in 20 cases and stromal changes in nine cases. In addition, trephine biopsy picked up residual leukemic blasts in four cases in which aspirate showed remission status. Post-induction marrow IHC with scattered positivity for blasts showed sustained remission in 96% cases, and in those with clustered positivity, 28.6% showed residual disease, and 7.2% showed relapse at the end of the study period. The median survival duration was 13, 3, and 12 months for cases with sustained remission, residual disease, and relapse, respectively. There was a statistically significant difference in median survival of patients in the three groups (sustained remission, residual disease, and relapse) (p=0.000).ConclusionWe conclude that histomorphology augmented by IHC on trephine biopsy gives valuable information regarding post-chemotherapy changes and residual disease status. Bone marrow trephine biopsy is an important tool to assess the remission status of patients with acute leukemia.

EXTH-63. A NOVEL MOUSE MODEL OF DIFFUSE MIDLINE GLIOMA FOR TARGETED IMMUNOTHERAPY

Abstract In children, diffuse midline gliomas retain poor outcomes, failing to have a durable response to conventional therapies. Immunotherapies hold promise, with the integration of the host's immune system fundamental to their design. Here, we describe a novel genetically engineered immunocompetent model that incorporates interleukin 13 receptor alpha 2 (IL13Rα2), a tumor-associated antigen, to evaluate the antitumor activity of IL13Rα2-CAR T cell and bispecific T cell engager (BiTE) therapies in preclinical studies. The RCAS-Tva delivery system was utilized to induce gliomagenesis through p53 loss and the constitutive expression of PDGFB and human IL13Rα2 in Nestin-Tva;p53fl/fl mice. Pups were injected with virus-producing DF1 cells, encoding either for RCAS-Cre and PDGFB+IL13Rα2 or RCAS-Cre and PDGFB. Kaplan-Meier survival curves established and compared tumor growth dynamics in both models. Tumor tissue was characterized through immunohistochemistry and H&amp;E staining. Cell lines generated from tumor-bearing tissue were used for orthotopic injection and in vitro studies. Expression of PDGFB and IL13Rα2 was confirmed by flow cytometry and western blot. In both groups, de novo tumors developed without significant difference in median survival between RCAS:PDGFB (n=25, 40 days) and RCAS:PDGB+IL13Rα2 (n=32, 39 days). Tumors demonstrated characteristics of high-grade glioma such as infiltration, pseudopalisading necrosis, microvascular proliferation, high Ki-67 index, heterogenous IL13Rα2 expression, with notable presence of CD11b+ macrophages and low count of CD3+ T cells. Orthotopic tumors from developed cell lines were histologically similar to de novo tumors. Treatment of generated cell lines with IL13Rα2-targeting BiTE protein resulted in a loss of glioma cell viability and target-specific activation of T cells. Engineered de novo tumors possess histopathologic features common to diffused midline gliomas. IL13Rα2-positive cell lines derived from de novo tumors were responsive to targeted treatment, opening the opportunity for preclinical assessment of IL13Rα2-directed immunotherapies, with the potential for clinical translation.