5-year Overall Survival Of Patients Research Articles

8061 Factors Affecting Survival of Metastatic Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program

Abstract Disclosure: A. Abdelhameed: None. H. Ibrahim: None. M. Mortagy: None. Introduction: Medullary thyroid cancer (MTC) arises from parafollicular cells of the thyroid. 43% of patients with MTC have metastasis. It was shown that the overall 5-year survival of patients with MTC is 40.4%. The clinical course of MTC is highly variable. The Aim is to identify factors affecting survival of the metastatic MTC sub-population. Understanding these factors is important in treating these patients. Methods 340 patients: with metastatic MTC who were diagnosed from 1975 to 2020 were extracted from SEER after removing duplicates and those not diagnosed by positive histology or cytology. Survival analysis was conducted, and Kaplan-Meier graph was generated. Univariate Cox regression was performed for all variables and respective hazard ratios (HR) were produced. Multivariable cox regression was performed for statistically significant variables. Results: The cohort were 59% males with a median age of 60 years. Median survival for the cohort was 20 months with survival of 63%, 41% and 31% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.02), brain metastasis (HR 2.70), liver metastasis (1.65), lung metastasis (1.42), not performing total thyroidectomy (HR 2.77), lymph node ratio (HR 2.45), and systemic therapy after surgery (HR 0.34). Univariate Cox regression was not statistically significant for sex, grade, radiotherapy, chemotherapy, treatment delay, bone metastasis, distant lymph node metastasis, multifocal cancer, total number of benign and malignant tumors, race/ethnicity, income, tumor size and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for age (HR 1.04), presence of lung metastasis (HR 1.91), and systemic therapy before surgery (HR 14.41). Conclusion: Increasing age, presence of lung metastasis and systemic therapy before surgery lead to worse prognosis in metastatic MTC. Gender, grade, radiotherapy, chemotherapy, treatment delay, bone or brain or liver metastasis, presence of multifocal cancer, race, tumor size and surgery don't affect survival according to multivariable cox regression. Future research is needed to study this group of patients. Presentation: 6/2/2024

Does Hepatic Metastasectomy for Breast Cancer Oligo-Metastasis to the Liver Offer Survival Advantage? Systematic Review and Meta-Analysis

Abstract Background: The impact of liver resection on survival in patients with hepatic metastasis from breast cancer has remained a controversial topic, with multiple studies reporting conflicting results. Objective: We perform this meta-analysis comparing metastasectomy to systemic therapy in terms of survival outcomes in cases of hepatic oligo-metastasis from breast cancer. Materials and Methods: A systematic search of PubMed, Embase, and Cochrane Library was conducted for relevant studies. The search terms used included “Breast Neoplasms,” “Liver,” hepatic” “Metastasis” “Hepatectomy,” “Metastasectomy” “resection,” and “surgery.” The primary outcome was overall survival (OS). Only studies published in English and studies that compared OS between patients that had metastasectomy and those that received systemic therapy were included. Results: Thirteen studies were included in the meta-analysis. The one year overall survival of patients who had surgery is superior to those who received systemic therapy only, with a risk ratio (RR) of 7.59 and P value of <0.00001. There is also a superior overall survival at 3 years after metastasectomy when compared with patients that received systematic therapy (RR = 2.83, P = 0.005). Five years is also superior, with RR of 2.78 and P value of 0.005. Conclusion: Hepatic metastasectomy in combination with systemic therapy is superior to systemic therapy alone in patients with breast cancer and oligo-metastasis of the liver.

Survival among 148 patients with an incidentally detected appendiceal tumours at surgery for acute appendicitis: a population-based cohort follow-up study.

To investigate the long-term prognosis of appendiceal tumours incidentally detected at appendicectomy for suspicion of benign appendicitis. A retrospective register-based single centre cohort study was carried out, using data from the local acute appendicectomy quality register of cases operated on at the Department of Surgery, South General Hospital, Stockholm, Sweden. The local colorectal cancer register was also used to identify appendix tumours. The study period was between January 2004 and January 2023. Survival was calculated according to the Kaplan-Meier method. A total of 11,888 patients were registered in the acute acute appendicectomy register, 54% males and 46% females, median age 32 (Q1 = 21, Q3 = 47) (with 33.7% were 41 years or older). From the appendicectomy and colorectal registers 148 (1.2% of the total cohort) appendiceal tumours were found; 60% in females and 40% in males, median age 56 (Q1 = 43, Q3 = 70) (with 78.4% being 41 years or older). Tumours found were: Low grade Appendiceal Mucinous Neoplasms (LAMN, N = 64); Neuroendocrine Tumours (NET N = 24); adenocarcinomas or other form of carcinomas (N = 57); and adenomas (N = 3). The overall 5-year survival in patients operated for LAMN was 96.8%, for NET 93.3% and for adenocarcinoma 69.7%. The overall 5-year survival for all tumour patients was 85.7%. For the younger patients (< 51 years) with LAMN and NET, almost all survived to the end of follow-up. Survival of patients in the carcinoma group was statistically significantly lower than for the LAMN and NET groups, especially in females 51 years or older. In the group of tumour patients undergoing surgery (n = 146), primary surgery was laparoscopic in 47% and open in 52%. Two patients did not undergo surgery due to widespread disease. In 64% of cases operation was acute, whereas it was delayed and/or planned in 34%. Most procedures were laparoscopic appendicectomy 36%, followed by open appendicectomy 30%, right-sided hemicolectomy 14.6% (open 11.6% and laparoscopic 3%, acute operation 5.5%), ileocaecal resection 5% (acute operation 3.4%), and staging laparoscopy 7%. In 38% of the operated patients the tumour was discovered incidentally at histopathology examination. Two patients had CRS and HIPEC as the initial operation. Forthy-three per cent of the 146 tumour patients operated underwent a second procedure: CRS and HIPEC in 23.3% and right-sided hemicolectomy in 13.6% (laparoscopic 8.2% open 5.4%). Survival was high for patients with incidentally detected appendiceal LAMN or NET, but not so for carcinoma. Survival was lower in the carcinoma group older than 50 years, especially those sick and females.

327 Impact of Adjuvant Chemotherapy/Radiotherapy on the 5 Year Overall Survival of Patients with Non-Metastatic Rectal Cancer in Bulgaria - a Retrospective Population-Wide Observational Study

Abstract Introduction Survival rates of patients with non-metastatic rectal cancer (RC) have increased, due the use of adjuvant chemotherapy/radiotherapy post-surgery, recommended by the National Comprehensive Cancer Network (NCCN) [1–3]. The aim of the study was to analyse the impact of adjuvant chemotherapy/radiotherapy on the 5-year overall survival (OS) of patients diagnosed with non-metastatic RC patients in Bulgaria. Method This is a retrospective population wide observational study of 8968 cases registered with Colorectal cancer in the Bulgarian National Cancer Registry (BNCR) between 2015 and 2016. The mean and median age of patients with left colon (LCC) and right colon (RCC) along with rectal cancer (RC) was analysed. The impact of adjuvant chemotherapy and radiotherapy on the 5-Year OS for non-metastatic RC was analysed. Kaplan-Meier curve with log rank, ANOVA and chi-squared tests were used to estimate the statistical significance. Results The mean age at diagnosis for RCC, LCC and RC was 68.9, 67.41 and 66.4 respectively (p-Value=&amp;lt;0.001). The median age at diagnosis was 69, 68 and 67 for RCC, LCC and RC respectively. Our study showed that patients with non-metastatic RC that received both adjuvant chemotherapy and radiotherapy had a higher 5-year OS compared to patients who received either chemotherapy, radiotherapy or neither therapy (61.4%, 59.5%, 56.2%, 51.8%), p-Value=0.007. Less than 40% of patients received either adjuvant chemotherapy or radiotherapy. Conclusions Adjuvant chemotherapy/radiotherapy improves the 5-Year OS for patients with non-metastatic RC. NCCN guidelines should be implemented in Bulgaria [1–3]. Bulgaria will benefit by implementing an organised screening programme [4].

Malnutrition is associated with poor survival in women receiving radiotherapy for cervical cancer

ObjectiveCancer patients are at risk of malnutrition, which is associated with poor oncological outcomes. The aim of this study was to assess the incidence of malnutrition before, during, and after...

Squamous cell carcinoma of the bladder: Demographics and outcomes associated with surgery and radiotherapy.

Squamous cell carcinoma of the bladder (SCCB) is a rare disease composing 2%-5% of all bladder cancers with no consensus regarding treatment. The present study aims to analyze the outcomes of established treatments, namely chemotherapy, radiation, and surgery, to guide clinical decision-making for patients with non-schistosomal SCCB. Patients with bladder SCC diagnosed between 2000 and 2018 were reviewed utilizing data from the Surveillance, Epidemiology, and End Results Registry (SEER) program. A total of 5653 patients with SCCB were identified; median survival was 13 months and was significantly decreased in patients treated with chemotherapy or radiation (median survival of 9 or 12 months, respectively). Patients treated with both surgery and radiotherapy saw a decreased 5 year overall survival (OS) of 14%, compared to 35% for those treated with surgery alone (p < 0.01). Furthermore, patients treated with surgery, chemotherapy, and radiotherapy saw a decreased 5 year OS of 20%, compared with 25% for those that received surgery and chemotherapy only (p < 0.01). Finally, surgical intervention provided an increased 5 year OS for patients with locoregional disease only; those with distant disease saw no increase in 5 year OS (p < 0.01). Based on this study's analysis, radical surgery may be the most effective treatment for this disease.

Survival nomogram for patients with thymic squamous cell carcinoma, based on the SEER database and an external validation cohort

ObjectiveThis study aimed to construct a nomogram to effectively predict the 3 years and 5 years overall survival of patients with thymic squamous cell carcinoma (TSCC).MethodFrom 2000 to 2019, a total of 355 patients with TSCC were enrolled in our research from the Surveillance, Epidemiology, and End Results (SEER) database and used as the training cohort. 106 patients were included from the Zhejiang Cancer Hospital, for the external validation cohort. A nomogram was constructed based on the risk factors affecting prognosis using a Cox proportional hazards regression model. The discrimination and calibration of the nomogram were evaluated by C-index and curve of calibration. The two cohorts were divided into low-risk and high-risk subgroups based on the median risk score.ResultsAge (p = 0.002), stage (p = 0.003), surgery therapy (p < 0.001), and radiotherapy (p = 0.030) were the independent prognostic factors for overall survival and were incorporated in the prognostic model. The discrimination of the nomogram revealed a good prognostic accuracy and clinical applicability as indicated by C-index values of 0.696 (95% confidence interval [CI] 0.676–0.716) and 0.717 (95% CI 0.640–0.794) for the training cohort and external validation cohort, respectively. In addition, the two cohorts were divided into a high-risk group and a low-risk group according to the median risk score. Significant differences in overall survival were observed between the high-risk and low-risk groups in the training (p < 0.0001) and external validation cohort (p < 0.0001).ConclusionWe developed a nomogram to predict 3- and 5 year survival rate for TSCC. This nomogram provides a convenient and reliable tool for assessing the condition of patients with TSCC and assisting clinicians in making decisions.

Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review

The most common primary liver cancer is hepatocellular carcinoma (HCC), and its mortality rate is increasing globally. The overall 5-year survival of patients with liver cancer is currently 10-20%. Moreover, because early diagnosis can significantly improve prognosis, which is highly correlated with tumor stage, early detection of HCC is critical. International guidelines advise using α-FP biomarker with/without ultrasonography for HCC surveillance in patients with advanced liver disease. However, traditional biomarkers are sub-optimal for risk stratification of HCC development in high-risk populations, early diagnosis, prognostication, and treatment response prediction. Since about 20% of HCCs do not produce α-FP due to its biological diversity, combining α-FP with novel biomarkers can enhance HCC detection sensitivity. There is a chance to offer promising cancer management methods in high-risk populations by utilizing HCC screening strategies derived from new tumor biomarkers and prognostic scores created by combining biomarkers with distinct clinical parameters. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker in HCC. When combined with other clinical parameters, the detection of some biomarkers has higher sensitivity and specificity in comparison with a single biomarker. Therefore, newer biomarkers and models, such as the Lens culinaris agglutinin-reactive fraction of Alpha-fetoprotein (α-FP), α-FP-L3, Des-γ-carboxy-prothrombin (DCP or PIVKA-II), and the GALAD score, are being used more frequently in the diagnosis and prognosis of HCC. Notably, the GALAD algorithm was effective in HCC prevention, particularly for cirrhotic patients, regardless of the cause of their liver disease. Although the role of these biomarkers in surveillance is still being researched, they may provide a more practical alternative to traditional imaging-based surveillance. Finally, looking for new diagnostic/surveillance tools may help improve patients' survival. This review discusses the current roles of the most used biomarkers and prognostic scores that may aid in the clinical management of HCC patients.

Adenocarcinoma of the Gallbladder: A case of a rare metastasis to the thyroid

Gallbladder cancer is a rare and aggressive form of gastrointestinal malignancy, typically remaining asymptomatic making early diagnosis uncommon. Five year overall survival in patients with distant metastasis is 2% with a median survival of 5.8 months, with metastases typically identified in the liver and lung. Here we present the fourth case of metastases to the thyroid gland.

S263 Disparities in Survival and Stage at Diagnosis in Ethnic and Racial Minorities Diagnosed With Early Onset Colorectal Cancer

Introduction: Although the overall incidence of early onset Colorectal Cancer (eoCRC) is increasing, the incidence remains higher among Black and Hispanic patients than non-Hispanic whites. The aim of this study was to examine racial and ethnic disparities in the stage at diagnosis and survival of patients with eoCRC. Methods: We conducted a retrospective cohort study using the National Cancer Institute’s Surveillance, Epidemiology, and End Results 18 Registries (SEER 18) Program Research Plus database. We included all patients aged <50 years diagnosed with eoCRC from 2000-2017. Selected variables of interest included race/ethnicity, stage at diagnosis, and survival time. Survival analysis was limited to patients diagnosed between 2000-2012 to include minimum 5-year survival data. The study was certified exempt by the University of Washington IRB. Results: 71,651 patients were identified of whom 58.5% were non-Hispanic White (NHW) patients and 41.5% were racial/ethnic minorities. 24,229 patients had localized (stage I-IIc), 26,947 patients had regional (stage IIIa-c), and 17,805 patients had distant (stage IVa/b) eoCRC at diagnosis. Patients from racial/ethnic minorities were significantly more likely to be diagnosed with distant eoCRC compared to NHW patients (Table) (p< 0.01). These differences were greatest for non-Hispanic Black (NHB) patients. Overall as well as stage-specific 1-year and 5-year survival was significantly shorter in racial/ethnic minorities (Figure) (p< 0.01). These differences were again greatest in NHB patients. Conclusion: Significant differences in stage at diagnosis were seen between NHW and racial/ethnic minorities with eoCRC. Significant racial/ethnic differences were also seen in overall median survival and median survival at all stages of diagnosis. For both stage and survival, the greatest differences were seen in NHB patients followed by American Indian/Alaska Native patients. Further study is needed to understand the reason for these disparities.Figure 1.: Kaplan Meier curve depicting overall 5-year survival of patients with eoCRC stratified by race/ethnicity Table 1. - Stage at diagnosis, 1-year and 5 year survival rate of patients diagnosed with eoCRC stratified by race/ethnicity Stage Race/Ethnicity Portion of Racial/Ethnic Cohort 1-year Survival Rate 5-year Survival Rate Overall (n = 48,987) All Races/Ethnicities 100% 89.3% 66.6% Non-Hispanic White 100% 89.8% 68.4% Non-Hispanic Black 100% 85.6% 57.8% Hispanic (all races) 100% 89.3% 66.0% Asian of Pacific Islander 100% 91.0% 67.8% American Indian/Alaska Native 100% 87.4% 61.5% Unknown 100% 98.7% 97.4% Localized (n = 16,510) All Races/Ethnicities 33.7% 98.2% 91.6% Non-Hispanic White 34.3% 98.4% 92.3% Non-Hispanic Black 32.5% 97.1% 87.8% Hispanic (all races) 31.9% 97.9% 90.6% Asian of Pacific Islander 32.4% 99.2% 93.5% American Indian/Alaska Native 31.5% 95.3% 85.8% Unknown 13.7% 99.6% 99.6% Regional (n = 18,706) All Races/Ethnicities 38.2% 95.5% 74.9% Non-Hispanic White 38.8% 95.6% 76.7% Non-Hispanic Black 35.0% 93.8% 66.3% Hispanic (all races) 38.7% 95.7% 74.2% Asian or Pacific Islander 40.5% 96.4% 75.7% American Indian/Alaska Native 36.3% 94.0% 74.1% Unknown 13.7% 100% 96.2% Distant (n = 12,011) All Races/Ethnicities 24.5% 67.6% 19.3% Non-Hispanic White 23.7% 68.1% 20.2% Non-Hispanic Black 28.2% 62.2% 12.2% Hispanic (all races) 25.5% 69.3% 23.1% Asian or Pacific Islander 23.8% 71.2% 19.8% American Indian/Alaska Native 26.9% 68.3% 15.1% Unknown 3.7% 85.5% 64.3% Unstaged (n = 1,760) All Races/Ethnicities 3.6% 87.2% 67.0% Non-Hispanic White 3.2% 87.2% 67.9% Non-Hispanic Black 4.3% 84.7% 60.9% Hispanic (all races) 3.9% 87.4% 63.3% Asian or Pacific Islander 12.4% 86.3% 65.1% American Indian/Alaska Native 5.1% 97.5% 66.7% Unknown 20.3% 97.4% 97.4%

Recent Advances in DNA Vaccines against Lung Cancer: A Mini Review.

Lung cancer is regarded as the major causes of patient death around the world. Although the novel tumor immunotherapy has made great progress in the past decades, such as utilizing immune checkpoint inhibitors or oncolytic viruses, the overall 5-year survival of patients with lung cancers is still low. Thus, development of effective vaccines to treat lung cancer is urgently required. In this regard, DNA vaccines are now considered as a promising immunotherapy strategy to activate the host immune system against lung cancer. DNA vaccines are able to induce both effective humoral and cellular immune responses, and they possess several potential advantages such as greater stability, higher safety, and being easier to manufacture compared to conventional vaccination. In the present review, we provide a global overview of the mechanism of cancer DNA vaccines and summarize the innovative neoantigens, delivery platforms, and adjuvants in lung cancer that have been investigated or approved. Importantly, we highlight the recent advance of clinical studies in the field of lung cancer DNA vaccine, focusing on their safety and efficacy, which might accelerate the personalized design of DNA vaccine against lung cancer.

Netrin-1 induces the anti-apoptotic and pro-survival effects of B-ALL cells through the Unc5b-MAPK axis

BackgroundB-cell acute lymphoblastic leukemia (B-ALL) comprises over 85% of all acute lymphoblastic leukemia (ALL) cases and is the most common childhood malignancy. Although the 5 year overall survival of patients with B-ALL exceeds 90%, patients with relapsed or refractory B-ALL may suffer from poor prognosis and adverse events. The axon guidance factor netrin-1 has been reported to be involved in the tumorigenesis of many types of cancers. However, the impact of netrin-1 on B-ALL remains unknown.MethodsThe expression level of netrin-1 in peripheral blood samples of children with B-ALL and children without neoplasia was measured by enzyme-linked immunosorbent assay (ELISA) kits. Then, CCK-8 cell proliferation assays and flow cytometric analysis were performed to detect the viability and apoptosis of B-ALL cells (Reh and Sup B15) treated with exogenous recombinant netrin-1 at concentrations of 0, 25, 50, and 100 ng/ml. Furthermore, co-immunoprecipitation(co-IP) was performed to detect the receptor of netrin-1. UNC5B expression interference was induced in B-ALL cells with recombinant lentivirus, and then CCK-8 assays, flow cytometry assays and western blotting assays were performed to verify that netrin-1 might act on B-ALL cells via the receptor Unc5b. Finally, western blotting and kinase inhibitor treatment were applied to detect the downstream signaling pathway.ResultsNetrin-1 expression was increased in B-ALL, and netrin-1 expression was upregulated in patients with high- and intermediate-risk stratification group of patients. Then, we found that netrin-1 induced an anti-apoptotic effect in B-ALL cells, implying that netrin-1 plays an oncogenic role in B-ALL. co-IP results showed that netrin-1 interacted with the receptor Unc5b in B-ALL cells. Interference with UNC5B was performed in B-ALL cells and abolished the antiapoptotic effects of netrin-1. Further western blotting was applied to detect the phosphorylation levels of key molecules in common signaling transduction pathways in B-ALL cells treated with recombinant netrin-1, and the FAK-MAPK signaling pathway was found to be activated. The anti-apoptotic effect of netrin-1 and FAK-MAPK phosphorylation was abrogated by UNC5B interference. FAK inhibitor treatment and ERK inhibitor treatment were applied and verified that the FAK-MAPK pathway may be downstream of Unc5b.ConclusionTaken together, our findings suggested that netrin-1 induced the anti-apoptotic effect of B-ALL cells through activation of the FAK-MAPK signaling pathway by binding to the receptor Unc5b.-oqtjpF4fn996fXAD1ptLBVideo

MMAP-02 A POPULATION - BASED STUDY ON RADIATION THERAPY FOR BRAIN METASTASIS FROM MALIGNANT MELANOMA IN BRITISH COLUMBIA: EVALUATING THE IMPACT OF IMMUNOTHERAPY AND STEREOTACTIC TECHNIQUES

BACKGROUNDTo evaluate population-based outcomes for patients with brain metastasis from malignant melanoma, treated using radiation therapy, and to assess the impact of immunotherapy (IMT) and stereotactic radiation techniques (SRT). METHODSData was obtained from the BC Cancer Registry for all patients diagnosed with Melanoma in British Columbia, between 1st Jan 2005 and 31st Dec 2018. A total of 5133 patients were identified. These patients had received 2244 courses of RT, of which 461 were directed to the Brain, in 419 unique individuals. The median age was 62 years and majority, 89.5% (n=375), had cutaneous melanomas while 44 had mucosal or choroidal primary sites of disease. A total of 106 (25.3%) patients received IMT, and pembrolizumab was most commonly used (n=48). Over 85% of patients (n=358) received Whole Brain Radiation Therapy (WBRT) alone, with 20 Gy/5 being the most common dose fractionation. Stereotactic Radio-Surgery (SRS) or SRT alone was used in 31 patients, while 30 patients received a combination of SRS/SRT and WBRT. The most used fractionation for SRS was 30Gy/1 (n=9), and for SRT was 35 Gy/5 (n=25). Overall Survival (OS) was calculated from the date of starting radiation therapy. RESULTSAfter a median follow-up of 43 months (95% CI: 18.2 - 67.7), a total of 377 patients had died, with a Median Survival of 2 months (95% CI: 1.46 - 2.53 months) and a 2 year OS of 11.7%. On univariate analysis, age over 65, use of IMT, and SRS/SRT had a significant impact on 2-year OS (14.5% vs 7.4%, p<0.0001; 27.6% vs 6.7%, p<0.0001; and, 38.7% vs. 7.1% p <0.0001, respectively). These factors retained statistical significance on multi-variable analysis. The 2 year OS for patients who received IMT and SRS/SRT alone (n=22) was 54.7%. CONCLUSIONSelected patients treated aggressively with SRS/SRT and IMT have a median survival of >25 months and a 2-year OS > 50%.

MEDB-54. Standard Risk Medulloblastoma treated solely with surgery and chemo-radiation

INTRODUCTION: Medulloblastoma is the most common malignant brain tumor in children, with 5-year overall survival (OS) ranging from 60%-95% depending on subgroup and risk status. The POG 8631/CCG 923 trial (accrual 1986-1990) found a 63% 5 year OS for patients with local disease after gross total resection treated with radiation at a dose of 23.4 Gy craniospinal radiation and posterior fossa boost to 54 Gy, vs. 80.5% 5-year OS for patients treated as per full ACNS0331 therapy including maintenance chemotherapy. Herein, we describe a long-term survival with standard-risk medulloblastoma who only received surgical resection and radiation therapy. CASE: A 17-year-old male presented with acute onset of hypertension, bradycardia, headache, and blurry vision and was found to have a heterogeneously enhancing posterior fossa mass with mass effect on the fourth ventricle and hydrocephalus on brain MRI. He underwent gross total resection of the tumor and histopathology revealed medulloblastoma with classic and large cell features. Fluorescence in situ hybridization (FISH) was negative for MYC, MYCN amplification, or HER2 gain. Cerebrospinal fluid cytology was negative for neoplastic cells, and spinal MRI did not reveal any drop metastases. The patient initiated therapy per ACNS0331 with craniospinal irradiation posterior fossa boost. He also received weekly vincristine. After completion of radiation therapy, the family declined further chemotherapy despite medical advice. He had no evidence of relapse most recently at 51 months from completion of therapy. Next generation sequencing and methylation testing are currently pending. CONCLUSION: Current efforts aim at optimizing therapy based on molecular subgrouping, to minimize long-term adverse events associated with current therapies. We report a unique case of an adolescent male with an standard-risk medulloblastoma, who achieved remission with only radiotherapy. Further molecular tumor analysis may elucidate the response of the tumor.

GCT-07. Central nervous system germ cell tumors of children in Slovakia from 2000 to 2020

Abstract INTRODUCTION: Central nervous system germ cell tumors (CNS GCTs) are very heterogenous group of tumors, which are divided into two main subgroups - germinomas and non- germinomatous germ cell tumors (NGGCTs). NGGCTs consist of embryonal carcinomas, yolk sac tumors, choriocarcinomas, and teratomas - mature, immature, or with malignant transformation, as well as mixed types. CNS GCTs are rare tumors, accounting approximately for 4-5% of all brain tumors in children, with a peak of incidence between the ages of 10 and 15 years, affecting predominantly boys. METHODS: Retrospective study of a cohort of 34 patients, age 0-18 years old, with CNS germ cell tumors diagnosed and treated in one of three Slovak pediatric oncology centers over a 21-year period from 01/2000 to 12/2020. Treatment was done according to the SIOP strategy. RESULTS: Out of 34 patients 15 patients were treated in the largest center, in Bratislava and 19 patients in the remaining 2 centers. Germinomas occurred in 16 (47.1%) and non-germinomatous germ cell tumors in 18 (52.9%) patients, 7 of whom had teratomas. In our cohort, 24 patients (70.6%) survived with an average follow-up age of 8.5 years. Twenty two patients remain in the 1st remission of the disease, 2 patients got through after disease recurrence. Ten patients (29.4%) died, 9 patients due to disease progression and 1 patient due to treatment complications. CONCLUSION: The overall survival of children with CNS GCT is most dependent on the histologic subtype of the tumor. Overall survival in children with germinomas reaches 90% and with NGGCTs around 60-70%, depending on the extent of the disease. In our cohort, we have achieved 70.6% 5 year overall survival of patients.

Soft Tissue and Visceral Organ Sarcomas With BCOR Alterations.

Sarcomas with BCOR alteration are a heterogenous group characterized by changes including internal tandem duplications (ITDs) and recurring fusions with CCNB3, ZC3H7B, and other rare partners. With widespread genomic testing, these alterations are now associated with histologies such as Ewing-like sarcoma (BCOR::CCNB3), high-grade endometrial stromal sarcoma (ZC3H7B::BCOR), and clear cell sarcoma of kidney (BCOR-ITD). BCOR altered sarcomas of soft tissues and organs were identified through PubMed using keywords "Sarcoma (AND) BCOR" from 2005 through October 2021. Summary statistics and outcome data were calculated using STATA v12.1. Forty-one publications described 190 patients with BCOR altered soft tissue or organ sarcomas. BCOR-ITD was most common, followed by BCOR::CCNB3, ZC3H7B::BCOR. BCOR-ITD tumors occurred mainly in infants, BCOR::CCNB3 commonly occurred in adolescent young adults, and ZC3H7B::BCOR only in adults. The most common site for BCOR::CCNB3 fused tumors was extremity, BCOR-ITD kidney and ZC3H7B::BCOR uterus. Metastasis was rare in patients with BCOR::CCNB3. While most underwent resection and chemotherapy, few received radiation. Median follow-up of survivors was 24 months. Five year overall survival for patients with BCOR::CCNB3 fusions was 68% (95% confidence interval [CI]: 46%-83%). Patients with BCOR-ITD and ZC3H7B::BCOR had worse prognoses with 5 years overall survival of 35% (95% CI: 15%-56%) and 41% (95% CI: 11%-71%), respectively, demonstrating need for collaborative efforts identifying optimal treatments to improve outcomes.

Does Metabolic Syndrome Effect the Perioperative Course and Costs of Patients With Hepatocellular Carcinoma Undergoing Robotic Hepatectomy? A Propensity Score-Matched Analysis.

This study was undertaken to examine the postoperative outcomes, costs, and survival after robotic hepatectomy for hepatocellular carcinoma (HCC) in patients with or without metabolic syndrome. Following IRB approval, we prospectively followed 56 patients undergoing robotic hepatectomy for HCC from 2016-2020. Patients with metabolic syndrome were compared to patients without metabolic syndrome regarding postoperative clinical outcomes, costs, and survival. Propensity score matching of a 1:1 ratio matched patients with and without metabolic syndrome according to 6 variables. 17 patients were matched to each arm. Mean age was 64 ± 14.0years and 30 patients (88%) had operations that were classified as advanced (IWATE 7-9) or expert (IWATE 10-12). There were no differences between patients with metabolic syndrome versus patients without metabolic syndrome in terms of operative duration (306 [301 ± 76.2] vs 239 [260 ± 116.9] minutes; P = 0.23), estimated blood loss (300 [321 ± 195.5] vs 200 [214 ± 151.4] ml; P = 0.08), conversion to "open" operation (1 [6%] vs 1 [6%]; p = 1.00), tumor size (5 [5 ± 3.0] vs 3 [4 ± 2.2] cm; P = 0.28), postoperative complications with Clavien-Dindo Score (≥III) (0 vs 1; P = 1.00), in-hospital mortality (0 [0%] vs 1 [6%]; P = 1.00), length of stay (5 [5 ± 1.7] vs 4 [5 ± 4.4] days; P = 1.00), and 30-day readmissions (1 [6%] vs 1 [6%]; P = 1.00). There were no differences in overall costs and profit. There was no difference in 1-year, 2-year, and 3- year overall survival in patients with or without metabolic syndrome after robotic HCC resection (84% vs 77%, 84% vs 61%, and 45% vs 61%, P = 0.42). For patients with and without metabolic syndrome, robotic advanced/expert hepatectomy for HCC resulted in similar intra-operative metrics, postoperative outcomes, costs, and survival.

Prognostic Value of Cell-Surface Vimentin-Positive CTCs in Pediatric Sarcomas.

BackgroundDespite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as < 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety.MethodsHere, for the first time reported in the literature, we have enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients as a possible marker of disease.ResultsWe constructed a ROC with an AUC of 0.831 resulting in a sensitivity of 85.3% and a specificity of 75%. Additionally, patients who were deemed to be CSV+ CTC positive were found to have a worse overall survival compared to those who were CSV+ CTC negative. We additionally found the use of available molecular testing increased the accuracy of our diagnostic and prognostic tests.ConclusionsOur findings indicate that CSV+ CTCs have prognostic value and can possibly serve as a measure of disease burden.

Assessment Of The Hematopoietic Cell Transplantation Comorbidity Index In Older Patients Receiving Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is an established therapy for malignant and nonmalignant hematologic disorders. Reduced-intensity conditioning (RIC) regimens have expanded the use of HSCT to elderly and higher risk patients. However, HSCT still remains associated with a significant mortality and morbidity and the careful assessment of risks and benefits before transplantation is essential. Major factors which influence non-relapse mortality (NRM) and overall survival (OS) after HSCT are diagnosis, type of transplant, remission status and the patient's risk profile, which includes age and presence of comorbidities. The use of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) has been proposed to predict the probability of NRM and OS following HSCT. However, the HCT-CI usefulness for older patients receiving a reduced intensity allogeneic HSCT remains unclear. MethodsA retrospective medical record review was performed to collect data from patients who underwent an allogeneic HSCT at a large, urban, NCI Comprehensive Cancer Center during a five year period (January 2005 to December 2010). Patients 55 years and older who were transplanted using RIC for a hematologic malignancy were selected to be analyzed. Comorbidities and test results were collected to determine the HCT-CI score and other clinical data collected included disease and remission status at time of transplant. Results85 patients aged >55 years old who received a RIC HSCT for hematologic malignancies between January 2005 to December 2010 were analyzed. The median patient age at the time of transplantation was 63 years (range: 55-75 years). The patient diagnoses included AML (39%), NHL (29%), MM (9%), MDS (11%), CLL (8%), ALL (4%). The median pre-transplantation HSCT-CI score was 2 (range: 0-9). Among 85 patients, OS at 2 years was 44%. The 2 yr OS was 31%, 37% and 44% in the low-, intermediate-, and high-risk HSCT-CI groups (p = 0.61), respectively. The corresponding NRM at 2 years was 25%, 17% and 18% (p = 0.91). We found no predictive value of HSCT-CI for either OS or NRM in older patients having an allogeneic HSCT with reduced-intensity condition. Stratification of age (55-59, 60-64, and 65+) showed no significant impact on 2 yr OS or NRM. However, there was a trend towards a better 2 yr OS for patients who had achieved a CR versus no CR at time of transplant (48% vs 41%). ConclusionOlder patients with hematologic malignancies represent a highly selected cohort, with the prospect of an allogeneic HSCT often considered too high-risk. A method to reliably stratify these older HSCT candidates is greatly needed. However, the HCT-CI score in this retrospective analysis did not help predict their NRM or 2 year OS for patients 55 years and older with hematologic malignancies receiving a reduced intensity HSCT. Further research is warranted into what combination of factors may provide a reliable predictive score for older patients with hematologic malignancies. Disclosures:Mehta:Millennium: Speakers Bureau; Celgene: Speakers Bureau.

Busulfan Targeted Dose In Hematopoietic Stem Cell Transplantation: The Impact In Toxicity, Sinusoidal Obstructive Syndrome and Survival

Introduction Busulfan (BU) is one of the most used alkylating agent in mieloablative conditioning regimens (CR) for patients submited to Hematopoietic Stem Cell Transplantation (HSCT). Its therapeutic effect is correlated to area under the curve (AUC) having a wide variability among patients. Ideal AUC is not been well stablished yet but it is known that higher levels can impact survival by increasing extra medular toxicity. In the other way, lower levels can be associated to a higher incidence of relapse. Two BU formulations are available, oral (PO) or Intrvenous (IV). Although IV BU can developed more reliable AUC, there are few data comparing both formulations. Objectives To compare the pharmacokinetics (PK) of PO and IV BU based conditioning regimens in patients submited to HSCT and to determinate the best target BU AUC in order to reduce acute toxicity after HSCT. Methods and Results 149 patients were prospectively evaluated. All recieved myeloablative (MA) BU based conditioning regimen (BU associated to Cyclophosphamide(Cy), Melphalan(Mel), Cy/VP-16, Fludarabine(Flu)/Thiotepa, Flu/Mel,Mel/Gencitabine, Mel/Cy, Flu/clofarabine, Clofarabine/Thiotepa). 56 (37,5%) received a MA reduced intensity CR (Bu associated to Flu). 56 (37.5%) patients recieved a stem cells from a matched related donor, 45(30.2%) from matched unrelated donor, 9(6%) from related haploidentical donor and 17 (11.4%) from cord blood. The median age was 30,2 years (range 1,3-73). 86 (57.7%) had acute leukemias and myelodisplastic syndrome, 28(18.8%) had lymphomas, multiple myeloma and chronic leucemias, 32(21.4%) had diferente benign diseases. 83 (55.7%) patients recieved PO and 63(44.3%) IV BU. All patients had BU PK monitoring at least one time during CR. 81 (54.4%) patients also performed a pre transplant BU test dose (32mg/m2 for IV and 1mg/kg for PO BU). There were 3 BU targeted AUC: 4000, 5000 and 6000 µMol.min, according to institutional protocols based on disease risk and patient age. Historical control of 53 patients who received myeloablative conditioning regimen with no BU PK monitoring were used. Mucositis, Sinusoidal obstruction Syndrome (SOS) Overall survival (OS), Transplant related mortality (TRM) and relapse were analysed according to AUC targeted dose. 184 (91%) patients developed mucositis at 5 (range:0-11) days after HSCT. There were no diference in either incidence (p=0,15) or severity (p=0,19) of mucositis in patients recieving PO(n=66, 32.6%) or IV (n=83, 41%) BU and historical control (n=53, 26.2%) (p=0,15). Pre transplant test dose had also no impact on incidence and severity of mucositis (p=0,75). More importantly, AUC targeted dose had no impact in either mucositis incidence or severity (p=0.75). Among all 202 patients, 23 (11,4%) developed SOS until day 30 post HSCT. The use of pre transplant Bu test dose had no impact in SOS incidence: Gray-subhazard ratio (SHR)SHR 0.70 - CI95% 025-1.91; (p=0.48). BU formulations (PO or IV) had no impact in SOS (p=0.73) either. Patients recieving higher BU AUC targeted dose had an incresed risk to develop SOS after HSCT: Incidence of SOS in patients who recieved AUC =5000 was 5% and 16% respectively (SHR 3.39, p=0.034, CI 95% 1.09-10.52). In contrast, this finding had no impact in day Transplant related TRM and 1 year OS: patients who revieved AUC =5000, had 1 year OS of 61% and 66% respectivelly (p=0.52). Patients who revieved AUC =5000, had 100 day TRM of 12% and 12% respectivelly (p=0.42). We also found that patients who recieved AUC from 4000 to 5000 had a lower OS, showing a protective effect of lower AUC: 1 year OS for patients who recieved AUC 4000t to 5000 was 65% (IC95% 55-74%) HR: 0.65, (p=0.33). In the other hand, patients who recieved lower AUC targeted dose (4000) had higher incidence of relapse: SHR: 0.42, p=0.08, CI 95% 0.15-1.1 Conclusion In this cohort of patients, toxicity and survival were not influenced by BU formulation (oral or IV). More importantly, patients recieving higher Bu AUC targeted dose had higher incidence of SOS and targeting AUC between 4000 to 5000 had a positive impact in 1 year OS but are more likely to relapse (AUC 4000). We also, shown that using Bu test dose, does not increase toxicities or mortality in patients reciving Bu condicioning regimen. Therefore, we can conclude that PK Bu monitoring is important in either PO or IV BU formulation, in order to reduce toxicities such as SOS and mortality. Disclosures: Santos: Novartis: Consultancy, Research Funding, Speakers Bureau.