Purpose Type 2 endoleak (T2EL) is the most common type of endoleak after endovascular abdominal aortic aneurysm repair (EVAR), and increases the risk of aneurysm sac rupture if it persists beyond 6 months. The purpose of this study is to compare the efficacy and safety of direct sac puncture versus transarterial embolization of T2ELs. Methods Retrospective review of 42 consecutive T2EL embolization procedures, 19 by DSP and 23 by transarterial technique, between January 2015 and December 2020. Primary outcome was aneurysm sac stability and resolution of endoleak at follow-up imaging. Adverse events (AE) were classified based on the Society of Interventional Radiology (SIR) practice guidelines. Results Technical success was 94.7% (18/19) in the DSP group and 86.9% (20/23) in the transarterial group ( p = 0.32 (−0.77–0.25)). Treatment efficacy was evaluated in 16 patients in the DSP group and 18 patients in the transarterial group who had follow-up imaging ≥6 months after embolization. Mean imaging follow-up was 17.1 ± 11.2 (range, 6–41) months in the DSP group and 26.5 ± 15.4 (range, 6–48) months in the transarterial group ( p = 0.06, −19.24–0.37). Treatment efficacy was 75% (12/16) in the DSP group and 33.3% (6/18) in the transarterial group ( p = 0.02, 95% CI, 0.09–0.97). There was no procedure-related mortality. Moderate-severe AE occurred in 15.7% (3/19) in the DSP group and 8.7% (2/23) in the transarterial group ( p = 0.44, −0.12–0.26). Conclusion In this study, DSP embolization of T2EL was equally safe and more effective than transarterial embolization in achieving aneurysm sac stability and resolution of endoleak.

Contains SOPs for Needle Core Biopsy Collection.

exome sequencing results of rrDLBCL

The purpose of this study is to evaluate the accuracy and interobserver agreement of ccLS in diagnosing clear cell renal cell carcinoma (ccRCC). This retrospective single-center study evaluated consecutive patients with solid renal masses who underwent mpMRI followed by percutaneous biopsy and/or surgical excision between January 2010 and December 2020. Predominantly (> 75

Supplemental methods Supplemental Figures Supplemental Figure S1. Overview of somatic copy number alterations in rrDLBCLs. Supplemental Figure S2. Consistent low coverage in the first exon of FOXO1. Supplemental Figure S3. Overview of FOXO1 mutations in rrDLBCLs. Supplemental Figure S4. VAFs corrected using purity estimates. Supplemental Figure S5. Somatic copy number alterations affecting lymphoma-related genes. Supplemental Figure S6: Recurrent deletions in NFKBIE. Supplemental Tables Supplemental Table S1. Clinical details and sample processing of 38 patients with relapsed or refractory DLBCL and TLy Supplemental Table S2. Characteristics of samples used for exome sequencing and targeted sequencing of selected genes.

Targeted sequencing of untreated DLBCL and TLy

Contains SOPs for collection and processing of peripheral blood.

Contains SOPs for isolation of DNA and RNA.

Contains SOPs for Needle Core Biopsy Collection.

targeted sequencing results of rrDLBCL

Contains SOPs for Shipping of Biopsies and Blood.

Contains quality control metrics from the Agilent microarrays.

AbstractBackgroundTherapeutic resistance is the main cause of death in metastatic colorectal cancer. To investigate genomic plasticity, most specifically of metastatic lesions, associated with response to first‐line systemic therapy, we collected longitudinal liver metastatic samples and characterized the copy number aberration (CNA) landscape and its effect on the transcriptome.MethodsLiver metastatic biopsies were collected prior to treatment (pre, n = 97) and when clinical imaging demonstrated therapeutic resistance (post, n = 43). CNAs were inferred from whole exome sequencing and were correlated with both the status of the lesion and overall patient progression‐free survival (PFS). We used RNA sequencing data from the same sample set to validate aberrations as well as independent datasets to prioritize candidate genes.ResultsWe identified a significantly increased frequency gain of a unique CN, in liver metastatic lesions after first‐line treatment, on chr18p11.32 harboring 10 genes, including TYMS, which has not been reported in primary tumors (GISTIC method and test of equal proportions, FDR‐adjusted p = 0.0023). CNA lesion profiles exhibiting different treatment responses were compared and we detected focal genomic divergences in post‐treatment resistant lesions but not in responder lesions (two‐tailed Fisher's Exact test, unadjusted p ≤ 0.005). The importance of examining metastatic lesions is highlighted by the fact that 15 out of 18 independently validated CNA regions found to be associated with PFS in this study were only identified in the metastatic lesions and not in the primary tumors.ConclusionThis investigation of genomic‐phenotype associations in a large colorectal cancer liver metastases cohort identified novel molecular features associated with treatment response, supporting the clinical importance of collecting metastatic samples in a defined clinical setting.

Introduction: We have previously defined ‘next generation specimens’ as longitudinal biopsy samples collected at different time points during the disease trajectory, in a specific treatment context, either for discovery research or to guide clinical decisions (Basik, M. et al. Nat Rev Clin Oncol. 2013). The objective of the present study was to track tumor evolution at the copy number (CN) level and capture emerging resistance mechanisms in metastatic colorectal cancer (mCRC) using a standardized collection of high-quality metastasis samples, at baseline and at the time of clinical resistance, in the context of a phase IV multicenter clinical trial (NCT00984048). Methods: One hundred and forty fresh frozen liver metastasis (LM) specimens collected at baseline (pre, n = 97) and at the time of clinical resistance (post, n = 43) from 119 mCRC patients undergoing standard first-line therapy were profiled using whole exome sequencing and characterized for CN variation using Nexus Copy Number software. RNA sequencing data available for the same sample set allowed filtering the CN aberration (CNA) candidates for mRNA correlation in each analysis performed. Objective response was attributed based on the RECIST v1.0 criteria. Genomic Identification of Significant Target in Cancer (GISTIC) test was used to identify focal CNA. CNA frequency reported as being significantly different between 2 groups met a minimum p-value of 0.005 on a two-tailed Fisher’s exact test. The log-rank test was used to identify CNA associated with progression-free survival (PFS). The threshold used for significance was permutated p-value < .005. Results: The CN variation landscape of 97 pre LM samples confirmed the most common chromosome (chr) arm amplifications being on chr 7p, 7q, 8q, 13q, and 20q and the most frequent deletions on chr 1p, 1q, 4p, 4q, 8p, 17p, 18p, 18q, and 22q. Twenty-nine focal aberrations were also identified by GISTIC. Comparative analyses identified 22 focal CNA with significantly different frequencies between pre- and post- samples. The comparison between partial responder (PR, n = 47) and intrinsically resistant (IRES, n = 5) lesions revealed 34 CNA with different frequencies at baseline. Acquired resistant (ARES) and IRES post-samples (n = 8) showed significant enrichment in 36 CNA compared to pre-sample (n = 97), and these CNA were not captured when PR (n = 10) post-samples are compared to pre-samples. One hundred thirty-seven CNA regions were found to be significantly associated with PFS. Interrogation of primary tumors and LM data available in public databases validated the predictive potential of 18 regions and also revealed the metastasis specificity of 15 of them. Candidate genes in these regions with concordant genomic/transcriptomic aberrations were identified. Conclusion: Our effort to collect and profile next-generation biospecimens provided global genomic and transcriptomic data of the largest LM cohort to date. By analyzing the association between molecular aberrations and patient outcomes, we identified novel biomarker candidates predictive of drug response in LM samples, supporting the utility of collecting metastatic samples in clinical settings.

Introduction: Metastatic colorectal cancers (mCRC) are highly heterogeneous, representing a challenge in treatment management. Studies have largely investigated the genomic landscape of primary tumors at diagnosis. As metastasis is responsible for 90% of cancer patient deaths, this highlights the need to characterize the genomic landscape of metastasis over time of treatment to decipher their evolution and role in therapeutic resistance. Methods: Metastatic liver tissue samples were collected at baseline (pre-biopsies) and at relapse (post-biopsies) in responder and non-responder mCRC patients undergoing the same treatment. Paired pre/post biopsies were collected from 14 patients (4 of them had multiple post-biopsies) to assess intra-patient, inter-tumour and intra-tumour heterogeneity following treatment exposure. Biopsies were profiled using RNA and whole exome sequencing (WES) as well as high-density Single-Nucleotide Polymorphism (SNP) array. Results: Profiling of 45 samples with both high-density SNP array and WES revealed 97.4% similarity between both technologies in the identification of genes targeted by copy number (CN) changes. The metastatic and primary tumor had similar somatic copy number aberration (SCNA) profiles. Using chemo-naïve biopsies, we identified 120 CN gains and 47 CN losses that were significantly associated with patient progression free survival. Integrative analysis with transcriptomic data from the same samples revealed that only 10% of the CN gains and 17% of the CN loss regions showed concordance between SCNA and expression levels. Similarly, at the gene level, higher concordance between SCNAs and expression change was observed in CN deletions compared to CN amplifications (11% vs 4.2%), suggesting other regulatory mechanisms involved. Interestingly, some of the genes showing high correlation between SCNA and gene expression were previously known for their involvement in cancer such as MYC and CD44. For each paired sample pre/post or post/post from the same patient, we computed a heterogeneity score (HS) based on SCNA calling using as two parameters, identical type of event called and 70% reciprocal overlap. We found high temporal intra-tumor heterogeneity in our cohort with a mean value of HS = 0.84 (range: 0.47-0.98). As expected, we observed more heterogeneity when comparing intra-patient inter-tumors heterogeneity (mean = 0.89, range: 0.77-0.95). Interestingly, the intrinsically resistant lesion had a lower score, and pre/post samples from the same or different lesion having the same response to treatment were less heterogeneous. This implies that acquisition of resistance correlates with an increase in genomic changes. Conclusion: Overall, we showed that liver metastasis and primary tumors from mCRC patients have similar SCNA profiles. From a technical perspective, we concluded that the use of WES data to identify genes located in SCNAs (gain and loss) is comparable to high-density SNP array. From a clinical point of view, we showed that approximately 10% of the genes affected by SCNA showed concordant changes in expression and therefore the use of CN results may not be suitable for making therapeutic decision. Furthermore, the high intra-tumor heterogeneity observed following treatment exposure highlights the importance of post-treatment biopsies to identify and understand mechanisms of mCRC resistance.

Abstract Introduction: Colorectal cancer (CRC) is the third leading cause of cancer related deaths primarily due to its resistance to current treatments. Studies aiming at understanding mechanisms of resistance have largely investigated the genomic landscape of primary tumors at diagnosis. However, selective pressures during therapy can lead to the expansion of resistant clones and tumor heterogeneity. This highlights the need to characterize the molecular changes of metastasis over time of treatment and response to decipher tumor evolution and therapeutic resistance mechanisms. Methods: Metastatic liver tissue samples were collected at baseline (pre-biopsies) and at the time of resistance (post-biopsies) in responder and non-responder CRC patients undergoing the same first-line treatment. Paired pre/post biopsies were collected from 14 patients including 4 patients with multiple post-biopsies to assess temporal and spatio-temporal tumor heterogeneity following treatment exposure. Biopsies were profiled using exome and transcriptome sequencing as well as high-density Single-Nucleotide Polymorphism (SNP) array analysis to capture chromosomal anomalies, loss of heterozygosity and copy number (CN) variations. Results: Profiling of 45 samples with both high-density SNP array and exome sequencing revealed 97.4% similarity between both technologies in the identification of genes targeted by copy number changes. Using chemo-naïve biopsies, we identified 120 CN gains and 47 CN loss that were significantly associated with patient progression free survival. Integrative analysis with transcriptome data revealed that only 10% of the genomic CN gains and 17% of the CN loss correlated with their gene expression levels. Based on CN variants comparison between paired pre/post treatment samples, we found high temporal intra-patient heterogeneity over time of treatment. Interestingly, we observed a relationship between heterogeneity and tumor response; showing that acquired resistant tumors have the highest temporal variations. Conclusion: This study, using a multi-omic approach to profile serial liver metastatic samples in CRC patients, highlights the genomic changes in tumor composition after treatment exposure and constitutes an innovative approach to identify clinical biomarkers and molecular signatures of resistance. Citation Format: Mathilde Couetoux du Tertre, Maud Marques, Karen Gambaro, Michael Witcher, Benoit Samson, Bernard Lespérance, Yoo-Joung Ko, Richard Dalfen, Eve St-Hilaire, Lucas Sidéris, Félix Couture, Sabine Tejpar, Ronald Burkes, Mohammed Harb, Errol Camlioglu, Adrian Gologan, Vincent Pelsser, André Constantin, Suzan McNamara, Petr Kavan, Claudia Kleinman, Gerald Batist. Genomic profiling in serial metastatic colorectal tumors identifies copy number alterations and spatio temporal intra-patient heterogeneity profiles associated with clinical response. Q-CROC-01: NCT00984048 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-231.

e20588 Background: Crizotinib is the current first-line standard of care for ALK+ NSCLC with response rates reaching 65% [1] . However, most patients progress within 1 or 2 years and mechanisms of resistance remain unknown for approximately 30% of patients [2] . [1] Shaw et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. NEJM 368: 2385-2394, 2013. [2] Doebele et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 2012; 18:1472-1482 Methods: Eligible patients had locally advanced or metastatic ALK+ NSCLC. Patients were asked to undergo a repeat tumor biopsy at time of progression and serial bloods and archived primary tumor were collected. Responses were assessed by RECIST 1.1. ctDNA and protein expression on serial blood will be evaluated over the course of treatment. Tumors were profiled using exome sequencing and targeted genomic analysis to identify novel mutations associated with response. Results: 24 patients with stage IV adenocarcinoma received crizotinib as first-line (n = 22) and second-line (n = 2) treatment. Mean age was 60 y (range 41-80). 4% were smokers, 33.5% were former and 62.5% were never-smokers. At data cutoff (Jan 26, 2017), 16 patients have discontinued treatment (14 due to progression and 2 withdrew). The median PFS markedly differed in non-responders (patients with immediate progression) vs responders (patients with initial response or stable disease) (1.8 vs. 27 months). Profiling was performed to identify the genomic traits in tissue and blood that correlate to treatment response. Conclusions: We identified a previously unrecognized subset of patients treated with crizotinib with an exceptionally long PFS. We also observed a subset of patients intrinsically resistant to crizotinib despite harboring ALK+. There are no known predictive biomarkers which can identify patients that will have a long-lasting response or who may not derive benefit from crizotinib. The multi-omics profiling applied to these groups may provide novel insights into mechanisms of response and resistance to crizotinib. Clinical trial information: NCT02041468.

BACKGROUND: Epithelioid "aggressive" osteoblastoma (EOB) is a rare and more aggressive subtype of osteoblastoma (OB) with a higher recurrence rate, greater risk of malignant transformation, larger size, and greater intraoperative blood loss. The present case report illustrates that preoperative angioembolization of an EOB can be safely performed with low intraoperative blood loss. CASE DESCRIPTION: A 21-year-old male patient presented to our institution with a 4-month history of neck discomfort, radicular pain in the proximal right arm, and mild weakness of the right biceps and triceps muscles. Imaging was suggestive of EOB, and computed tomographyeguided biopsy confirmed the diagnosis. The patient underwent same-day preoperative angioembolization of the major feeding vessels and subsequent complete tumor resection. During the procedure, he experienced minimal blood loss and did not require blood transfusion. CONCLUSIONS: EOB is a highly vascular primary bony lesion. To minimize intraoperative blood loss, preoperative angioembolization should be considered in the treatment of cervical spine EOB.

Learning ObjectivesThe aim of this poster is-To present a novel method of treating Type 2 endoleak when endovascular access of the endoleak fails.-To present a series of 5 cases demonstrating that simultaneous US guided percutaneous embolization of type II endoleaks is a promising, and viable option performed at our institution.Background-Type II endoleaks are the most commonly encountered endoleaks. When possible, they are treated through an endovascular approach. However, not uncommonly, even seasoned interventionists fail to reach the endoleak due to unaccommodating vascular anatomy. Often, the patient is then brought back, and CT guided translumbar percutaneous embolization is attempted. At our institution, a direct percutaneous puncture and subsequent embolization of the aneurysmal sac is performed under ultrasound guidance, at the time of failed endovascular attempt, through an anterior approach.Clinical Findings/Procedure Details-In case of type II endoleak embolization failure through endovascular approach, using ultrasound guidance, a direct puncture of the aneurysmal sac is performed on the fluoroscopy table.-Once punctured, iodinated contrast is injected which visualizes endoleaks. In our experience, more numerous, previously unseen feeding vessels were visualized at this point.-Embolic agent such as thrombin or a mixture of n-butyl-2 cyanoacrylate and Lipiodol is injected directly into the aneurysm sac.-Using the intravascular access, angiography can verify completeness of embolization while maintaining percutaneous access.Conclusion and/or Teaching Points-Simultaneously using ultrasound-guided direct puncture after failed endovascular approach in order to access the endoleak, provides a safe and immediate means to treat difficult type 2 endoleak.-Another advantage is having dual imaging modalities at the interventionist’s disposal for better visualization and treatment of the endoleaks.-Thirdly, via direct puncture, previously non-visualized endoleaks can be treated as well in single procedure.-Finally, if desired, aneurysmal sac pressure can also be measured.Abstract No. 335 Learning ObjectivesThe aim of this poster is-To present a novel method of treating Type 2 endoleak when endovascular access of the endoleak fails.-To present a series of 5 cases demonstrating that simultaneous US guided percutaneous embolization of type II endoleaks is a promising, and viable option performed at our institution. The aim of this poster is -To present a novel method of treating Type 2 endoleak when endovascular access of the endoleak fails.-To present a series of 5 cases demonstrating that simultaneous US guided percutaneous embolization of type II endoleaks is a promising, and viable option performed at our institution. Background-Type II endoleaks are the most commonly encountered endoleaks. When possible, they are treated through an endovascular approach. However, not uncommonly, even seasoned interventionists fail to reach the endoleak due to unaccommodating vascular anatomy. Often, the patient is then brought back, and CT guided translumbar percutaneous embolization is attempted. At our institution, a direct percutaneous puncture and subsequent embolization of the aneurysmal sac is performed under ultrasound guidance, at the time of failed endovascular attempt, through an anterior approach. -Type II endoleaks are the most commonly encountered endoleaks. When possible, they are treated through an endovascular approach. However, not uncommonly, even seasoned interventionists fail to reach the endoleak due to unaccommodating vascular anatomy. Often, the patient is then brought back, and CT guided translumbar percutaneous embolization is attempted. At our institution, a direct percutaneous puncture and subsequent embolization of the aneurysmal sac is performed under ultrasound guidance, at the time of failed endovascular attempt, through an anterior approach. Clinical Findings/Procedure Details-In case of type II endoleak embolization failure through endovascular approach, using ultrasound guidance, a direct puncture of the aneurysmal sac is performed on the fluoroscopy table.-Once punctured, iodinated contrast is injected which visualizes endoleaks. In our experience, more numerous, previously unseen feeding vessels were visualized at this point.-Embolic agent such as thrombin or a mixture of n-butyl-2 cyanoacrylate and Lipiodol is injected directly into the aneurysm sac.-Using the intravascular access, angiography can verify completeness of embolization while maintaining percutaneous access. -In case of type II endoleak embolization failure through endovascular approach, using ultrasound guidance, a direct puncture of the aneurysmal sac is performed on the fluoroscopy table.-Once punctured, iodinated contrast is injected which visualizes endoleaks. In our experience, more numerous, previously unseen feeding vessels were visualized at this point.-Embolic agent such as thrombin or a mixture of n-butyl-2 cyanoacrylate and Lipiodol is injected directly into the aneurysm sac.-Using the intravascular access, angiography can verify completeness of embolization while maintaining percutaneous access. Conclusion and/or Teaching Points-Simultaneously using ultrasound-guided direct puncture after failed endovascular approach in order to access the endoleak, provides a safe and immediate means to treat difficult type 2 endoleak.-Another advantage is having dual imaging modalities at the interventionist’s disposal for better visualization and treatment of the endoleaks.-Thirdly, via direct puncture, previously non-visualized endoleaks can be treated as well in single procedure.-Finally, if desired, aneurysmal sac pressure can also be measured.Abstract No. 335 -Simultaneously using ultrasound-guided direct puncture after failed endovascular approach in order to access the endoleak, provides a safe and immediate means to treat difficult type 2 endoleak.-Another advantage is having dual imaging modalities at the interventionist’s disposal for better visualization and treatment of the endoleaks.-Thirdly, via direct puncture, previously non-visualized endoleaks can be treated as well in single procedure.-Finally, if desired, aneurysmal sac pressure can also be measured.