EMBR-03. PINEOBLASTOMA: A POOLED OUTCOME STUDY OF NORTH AMERICAN AND AUSTRALIAN THERAPEUTIC DATA

Abstract Background Pineoblastoma (PB) is a rare embryonal brain tumour most often diagnosed in young children. To date, no clinical trials have been conducted specific to pediatric PB. Collaborative studies performed over the past 30 years have included PB in studies accruing for other embryonal tumours, primarily medulloblastoma (MB), but also including the entity formerly known as CNS-PNET and atypical teratoid rhabdoid tumors. Each of these studies have included only a small number of children with PB, making clinical features difficult to interpret and determinants of outcome difficult to ascertain. Patients and Methods Published centrally reviewed series with sufficient treatment and outcome data from North American and Australian cases were pooled. To investigate associations between variables, Fisher’s exact and Wilcoxon-Mann-Whitney tests, and Spearman correlations were used as appropriate. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analysis. Results We describe a 30-year review of the reported clinical features of PB and a pooled centrally reviewed, cohort analysis of cases (n=178) from the Children’s Oncology Group (COG) (n=82) groups and several published, centrally reviewed institutional series (n=96). We find young children <3 years of age have a dramatically poorer outlook compared to older children (5-year OS 16.2% +/- 5.3% vs 67.3% +/- 5%) confirming new and novel approaches are needed in future clinical trials for this at risk group. Interestingly, male gender was predictive of worse outcome possibly suggestive of gender specific subgroup risks that needs validation in future studies. Assessment of radiation therapy is not possible as the vast majority of children under age three did not receive any form of radiation therapy. Conclusion Given the relative scarcity of this tumor and the emerging data on subgroups of pineoblastoma, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.

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Patterns of Care and Outcomes of Primary Adenoid Cystic Carcinoma of the Trachea

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894211008101 ◽

2021 ◽

pp. 000348942110081

Author(s):

Sara Behbahani ◽

Gregory L. Barinsky ◽

David Wassef ◽

Boris Paskhover ◽

Rachel Kaye

Keyword(s):

Radiation Therapy ◽

Adenoid Cystic Carcinoma ◽

Surgical Resection ◽

Proportional Hazards ◽

Invasive Disease ◽

Cox Proportional Hazards ◽

Tumor Diameter ◽

Adenoid Cystic ◽

Cox Proportional Hazards Models ◽

Age Of Diagnosis

Objective: Primary tracheal malignancies are relatively rare cancers, representing 0.1% to 0.4% of all malignancies. Adenoid cystic carcinoma (ACC) is the second most common histology of primary tracheal malignancy, after squamous cell carcinoma. This study aims to analyze demographic characteristics and potential influencing factors on survival of tracheal ACC (TACC). Methods: This was a retrospective cohort study utilizing the National Cancer Database (NCDB). The NCDB was queried for all cases of TACC diagnosed from 2004 to 2016 (n = 394). Kaplan-Meier (KM) and Cox proportional-hazards models were used to determine clinicopathological and treatment factors associated with survival outcomes. Results: Median age of diagnosis was 56 (IQR: 44.75-66.00). Females were affected slightly more than males (53.8% vs 46.2%). The most prevalent tumor diameter range was 20 to 39 mm (34.8%) followed by greater than 40 mm in diameter (17.8%). Median overall survival (OS) was 9.72 years with a 5- and 10-year OS of 70% and 47.5%, respectively. Localized disease was not associated with a survival benefit over invasive disease ( P = .388). The most common intervention was surgery combined with radiation therapy (RT) at 46.2%, followed by surgery alone (16.8%), and standalone RT (8.9%). When adjusting for confounders, surgical resection was independently associated with improved OS (HR 0.461, 95% CI 0.225-0.946). Tumor size greater than 40 mm was independently associated with worse OS (HR 2.808; 95% CI 1.096-7.194). Conclusion: Our data suggests that surgical resection, possibly in conjunction with radiation therapy, is associated with improved survival, and tumor larger than 40 mm are associated with worse survival.

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CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.202 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi51-vi51

Author(s):

Kristen Batich ◽

Duane Mitchell ◽

Patrick Healy ◽

James Herndon ◽

Gloria Broadwater ◽

...

Keyword(s):

Clinical Trials ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Recurrent Glioblastoma ◽

Cox Proportional Hazards Model ◽

Total N ◽

Dc Vaccine ◽

Dc Vaccines

Abstract INTRODUCTION Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. METHODS To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with primary GBM. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. RESULTS Our initial study was the phase II ATTAC study (NCT00639639; total n=12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning (P=0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR=0.820, P=0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n=24, unpulsed DC n=19; 24h, P=0.031 and 48h, P=0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td (P=0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). CONCLUSION We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM.

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Abstract 13950: Predicted Heart Mass and BMI: Evaluating Undersized Heart Transplantation in Obese vs. Non-Obese Patients

Circulation ◽

10.1161/circ.142.suppl_3.13950 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Samuel T Kim ◽

Mark R Helmers ◽

Peter Altshuler ◽

Amit Iyengar ◽

Jason Han ◽

...

Keyword(s):

Propensity Score ◽

Heart Transplantation ◽

Propensity Score Matching ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Obese Patients ◽

Heart Transplants ◽

Term Survival ◽

Heart Mass

Introduction: Although guidelines for heart transplant currently recommend against donors weighing ≥ 30% less than the recipient, recent studies have shown that the detriment of under-sizing may not be as severe in obese recipients. Furthermore, predicted heart mass (PHM) has been shown to be more reliable for size matching compared to metrics such as weight and body surface area. In this study, we use PHM to characterize the effects of undersized heart transplantation (UHT) in obese vs. non-obese recipients. Methods: Retrospective analysis of the UNOS database was performed for heart transplants from Jan. 1995 to Sep. 2020. Recipients were stratified by obese (BMI ≥ 30) and non-obese (30 > BMI ≥ 18.5). Undersized donors were defined as PHM ≥ 20% less than recipient PHM. Obese and non-obese populations separately underwent propensity score matching, and Kaplan-Meier estimates were used to graph survival. Multivariable Cox proportional-hazards analyses were used to adjust for confounders and estimate the hazard ratio for death attributable to under-sizing. Results: Overall, 50,722 heart transplants were included in the analysis. Propensity-score matching resulted in 2,214, and 1,011 well-matched pairs, respectively, for non-obese and obese populations. UHT in non-obese recipients resulted in similar 30-day mortality (5.7% vs. 6.3%, p = 0.38), but worse 15-year survival (38% vs. 35%, P = 0.04). In contrast, obese recipients with UHT saw similar 30-day mortality (6.4% vs. 5.5%, p = 0.45) and slightly increased 15-year survival (31% vs. 35%, P = 0.04). Multivariate Cox analysis showed that UHT resulted in an adjusted hazard ratio of 1.08 (95% CI 1.01 - 1.16) in non-obese recipients, and 0.87 (95% CI 0.78 - 0.98) in obese recipients. Conclusions: Non-obese patients with UHT saw worse long-term survival, while obese patients with UHT saw slightly increased survival. These findings may warrant reevaluation of the current size criteria for obese patients awaiting a heart.

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Pelvic Radiation Improves Local Control After Hysterectomy for Uterine Leiomyosarcoma: A 20-Year Experience

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181acae50 ◽

2009 ◽

Vol 19 (6) ◽

pp. 1080-1084 ◽

Cited By ~ 25

Author(s):

Ali Mahdavi ◽

Bradley J. Monk ◽

Jennifer Ragazzo ◽

Mark I. Hunter ◽

Scot E. Lentz ◽

...

Keyword(s):

Radiation Therapy ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

High Rate ◽

Entire Group ◽

Adjuvant Radiation ◽

Uterine Leiomyosarcoma ◽

Modest Improvement ◽

Adjuvant Radiation Therapy

Background:Uterine leiomyosarcoma (LMS) is associated with high rate of recurrence after surgical resection. The role of adjuvant radiation therapy in improving survival in women with uterine LMS is unclear.Methods:All cases of LMS treated from 1985 to 2005 at 11 regional medical centers were identified. Kaplan-Meier survival curves were constructed and compared with log-rank testing. Multivariate analysis was performed to account for the potential influence of confounding factors.Results:One hundred forty-seven patients with LMS were identified. The median age of diagnosis was 51 years with the stage distribution of stage I (n = 87), II (n = 9), III (n = 25), IV (n = 25), and unknown (n = 1). One hundred forty-three underwent total abdominal hysterectomy and bilateral salpingoophorectomy. Twenty-four (17%) of these patients received adjuvant pelvic irradiation, and 63 (44%) received adjuvant and/or palliative chemotherapy. With a median follow-up of 24 months (range, 1-249 months), the median survival for the entire group was 37 months. Cox proportional hazards modeling demonstrated the presence of high tumor grade and advanced stage adversely affected survival. Although the 5-year survival for patients who received adjuvant radiotherapy was significantly higher than those who did not (70% vs 35%), this survival advantage was not sustained as the curves crossed at 90-month follow-up. Pelvic recurrence rate was lower in the radiation group (18% vs 49%; P = 0.02).Conclusions:Adjuvant radiation therapy was associated with decreased pelvic failure and a modest improvement in 5-year survival, but did not impact overall survival with extended follow-up.

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Individualized Prediction of Survival Benefits of Pancreatectomy Plus Chemotherapy in Patients With Simultaneous Metastatic Pancreatic Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.719253 ◽

2021 ◽

Vol 11 ◽

Author(s):

Duorui Nie ◽

Guihua Lai ◽

Guilin An ◽

Zhuojun Wu ◽

Shujun Lei ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Size ◽

Proportional Hazards ◽

Survival Curve ◽

Characteristic Curve ◽

Cox Proportional Hazards ◽

Metastatic Pancreatic Cancer ◽

Calibration Plot ◽

Term Survival ◽

Good Ability

BackgroundMetastatic pancreatic cancer (mPC) is a highly lethal malignancy with poorer survival. However, chemotherapy alone was unable to maintain long‐term survival. This study aimed to evaluate the individualized survival benefits of pancreatectomy plus chemotherapy (PCT) for mPC.MethodsA total of 4546 patients with mPC from 2004 to 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. The survival curve was calculated using the Kaplan-Meier method and differences in survival curves were tested using log-rank tests. Cox proportional hazards regression analyses were performed to evaluate the prognostic value of involved variables. A new nomogram was constructed to predict overall survival based on independent prognosis factors. The performance of the nomogram was measured by concordance index, calibration plot, and area under the receiver operating characteristic curve.ResultsCompared to pancreatectomy or chemotherapy alone, PCT can significantly improve the prognosis of patients with mPC. In addition, patients with well/moderately differentiated tumors, age ≤66 years, tumor size ≤42 mm, or female patients were more likely to benefit from PCT. Multivariate analysis showed that age at diagnosis, sex, marital status, grade, tumor size, and treatment were independent prognostic factors. The established nomogram has a good ability to distinguish and calibrating.ConclusionPCT can prolong survival in some patients with mPC. Our nomogram can individualize predict OS of pancreatectomy combined with chemotherapy in patients with concurrent mPC.

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A case of long-term disease control in a patient with disseminated melanoma with synchronous detection of multiple brain metastases

Research n Practical Medicine Journal ◽

10.17709/2409-2231-2018-5-4-10 ◽

2018 ◽

Vol 5 (4) ◽

pp. 98-105

Author(s):

M. I. Kurzhupov

Keyword(s):

Clinical Trials ◽

Radiation Therapy ◽

Targeted Therapy ◽

Clinical Case ◽

Total Duration ◽

Skin Melanoma ◽

Synchronous Detection ◽

Term Survival ◽

Stage Of Diagnosis

The article presents clinical trials data of melanoma with brain metastasis and a clinical case of long-term survival of a patient with disseminated skin melanoma and synchronous multiple metastatic brain damage by controlling a tumor disease using modern antitumor treatment, including targeted therapy, immunotherapy, radiation therapy, radiosurgery and neurosurgery (at the stage of diagnosis). The total duration of life after detection of the disease is 22 months, with an expected 2-3 months.

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Prognostic value of the ALBI grade among patients with single hepatocellular carcinoma without macrovascular invasion

10.21203/rs.3.rs-30583/v1 ◽

2020 ◽

Author(s):

Heng Zou ◽

Wenhao Chen ◽

Huan Wang ◽

Li Xiong ◽

Yu Wen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Grading System ◽

Term Survival ◽

Proportional Hazards Regression ◽

Disease Outcomes ◽

Single Tumor

Abstract Overview and objective: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.

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Intoxicated Donors and Heart Transplant Outcomes: Long-Term Safety

Circulation Heart Failure ◽

10.1161/circheartfailure.120.007433 ◽

2021 ◽

Author(s):

David A. Baran ◽

Justin Lansinger ◽

Ashleigh Long ◽

John M. Herre ◽

Amin Yehya ◽

...

Keyword(s):

Drug Use ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Heart Transplants ◽

Term Survival ◽

Ischemic Time ◽

Cox Proportional Hazards Models ◽

Donor Shortage ◽

United Network

Background: The opioid crisis has led to an increase in available donor hearts, although questions remain about the long-term outcomes associated with the use of these organs. Prior studies have relied on historical information without examining the toxicology results at the time of organ offer. The objectives of this study were to examine the long-term survival of heart transplants in the recent era, stratified by results of toxicological testing at the time of organ offer as well as comparing the toxicology at the time of donation with variables based on reported history. Methods: The United Network for Organ Sharing database was requested as well as the donor toxicology field. Between 2007 and 2017, 23 748 adult heart transplants were performed. United Network for Organ Sharing historical variables formed a United Network for Organ Sharing Toxicology Score and the measured toxicology results formed a Measured Toxicology Score. Survival was examined by the United Network for Organ Sharing Toxicology Score and Measured Toxicology Score, as well as Cox proportional hazards models incorporating a variety of risk factors. Results: The number and percent of donors with drug use has significantly increased over the study period ( P <0.0001). Cox proportional hazards modeling of survival including toxicological and historical data did not demonstrate differences in post-transplant mortality. Combinations of drugs identified by toxicology were not associated with differences in survival. Lower donor age and ischemic time were significantly positively associated with survival ( P <0.0001). Conclusions: Among donors accepted for transplantation, neither history nor toxicological evidence of drug use was associated with significant differences in survival. Increasing use of such donors may help alleviate the chronic donor shortage.

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Impact of Cognitive Dysfunction on Survival in Patients With and Without Statin Use Following Carotid Endarterectomy

Neurosurgery ◽

10.1227/neu.0000000000000904 ◽

2015 ◽

Vol 77 (6) ◽

pp. 880-887 ◽

Cited By ~ 12

Author(s):

Eric J. Heyer ◽

Joanna L. Mergeche ◽

Shuang Wang ◽

John G. Gaudet ◽

E. Sander Connolly

Keyword(s):

Confidence Interval ◽

Carotid Endarterectomy ◽

Cognitive Dysfunction ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Rank Test ◽

Term Survival ◽

Asymptomatic Patients ◽

Statin Use

BACKGROUND: Early cognitive dysfunction (eCD) is a subtle form of neurological injury observed in ∼25% of carotid endarterectomy (CEA) patients. Statin use is associated with a lower incidence of eCD in asymptomatic patients having CEA. OBJECTIVE: To determine whether eCD status is associated with worse long-term survival in patients taking and not taking statins. METHODS: This is a post hoc analysis of a prospective observational study of 585 CEA patients. Patients were evaluated with a battery of neuropsychometric tests before and after surgery. Survival was compared for patients with and without eCD stratifying by statin use. At enrollment, 366 patients were on statins and 219 were not. Survival was assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards models. RESULTS: Age ≥75 years (P = .003), diabetes mellitus (P < .001), cardiac disease (P = .02), and statin use (P = .014) are significantly associated with survival univariately (P < .05) by use of the log-rank test. By Cox proportional hazards model, eCD status and survival adjusting for univariate factors within statin and nonstatin use groups suggested a significant effect by association of eCD on survival within patients not taking statin (hazard ratio, 1.61; 95% confidence interval, 1.09–2.40; P = .018), and no significant effect of eCD on survival within patients taking statin (hazard ratio, 0.98; 95% confidence interval, 0.59–1.66; P = .95). CONCLUSION: eCD is associated with shorter survival in patients not taking statins. This finding validates eCD as an important neurological outcome and suggests that eCD is a surrogate measure for overall health, comorbidity, and vulnerability to neurological insult.

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Abstract 25: Six-year Change in C-reactive Protein Levels and Risk of Incident Diabetes, Cardiovascular Events and Mortality

Circulation ◽

10.1161/circ.129.suppl_1.25 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Christina M Parrinello ◽

Pamela L Lutsey ◽

Christie M Ballantyne ◽

Aaron R Folsom ◽

James S Pankow ◽

...

Keyword(s):

Cardiovascular Disease ◽

Proportional Hazards ◽

Cohort Analysis ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

C Reactive Protein ◽

Baseline Measure ◽

Reactive Protein ◽

Inflammatory Status ◽

Increased Risk

Background: High levels of C-reactive protein (CRP) are associated with cardiovascular disease, diabetes and mortality. It is unclear whether changes in CRP or persistently high CRP are associated with these outcomes beyond the baseline measure. Methods: We conducted a prospective cohort analysis of 10,229 participants from the ARIC Study with two measurements of CRP six years apart (at visits 2 and 4, 1990-92 and 1996-98, respectively). CRP was categorized into two groups using a standard cut-point for defining high levels (≥3 vs. <3 mg/L). Six-year change in CRP was categorized as: persistently not high (<3 mg/L), decreasing (≥3 to <3 mg/L), increasing (<3 to ≥3 mg/L), and persistently high (≥3 mg/L). Cox proportional hazards models were used to assess the association between visit 2 CRP, visit 4 CRP and six-year change in CRP and each of the following outcomes from visit 4 through 2010: diabetes, coronary heart disease, ischemic stroke, heart failure and all-cause mortality. Models were adjusted for traditional risk factors at visit 2. Sensitivity analyses additionally adjusted for visit 4 covariates. Results: Persons with CRP ≥3 mg/L at visit 2 or 4 had higher risk of each outcome compared to those with CRP <3 mg/L ( Table ). We observed higher risk of all outcomes in persons with persistently high CRP, and of all outcomes except stroke in persons with increasing CRP, compared to those with CRP <3 mg/L at both visits ( Table ). Persons whose CRP decreased from high to <3 mg/L did not have significantly increased risk of cardiovascular outcomes or diabetes compared to those with CRP persistently <3 mg/L. Results were similar after adjusting for visit 4 covariates. Conclusions: Persons with sustained high levels of CRP or whose CRP increased to high levels had higher risk of diabetes, cardiovascular disease, and death, while those whose levels decreased from high to moderate or low were at lower risk. Multiple measures of CRP may better characterize inflammatory status and provide more comprehensive information regarding long-term risk.

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