PD-L1 genomic alterations (GA) in solid tumors and hematologic malignancies: A comprehensive genomic profiling (CGP) study.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 12092-12092
Author(s):  
Laurie M. Gay ◽  
David Fabrizio ◽  
Garrett Michael Frampton ◽  
Lee A. Albacker ◽  
Ethan Sokol ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Hematologic Malignancies ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Comprehensive Genomic Profiling

The prevalence of targetable genomic alterations is substantially high in rare tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13539-e13539
Author(s):  
Shuhang Wang ◽  
Ning Li ◽  
Rongrong Chen ◽  
Yue Yu ◽  
Yuan Fang ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Genomic Data ◽  
Tumor Type ◽  
Genomic Profiling ◽  
Rare Tumor ◽  
Genomic Alterations ◽  
Rare Tumors ◽  
Novel Treatment ◽  
Comprehensive Genomic Profiling ◽  
Chinese Cohort

e13539 Background: Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcome for patients with rare solid tumors. This study aims to discover opportunities for use of targeted therapies currently in routine practice in patients with rare tumors. Methods: Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiology data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal was compared with that of Chinese population for targetable genomic alterations (TGAs). TGAs was defined as mutations of ALK, ATM, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, FGFR1,2,3, KIT, MET, NF1, NTRK1,2,3, PIK3CA, PTEN, RET, and ROS1 with level 1 to 4 of evidence according to OncoKB knowledge database. Results: Genomic data of 4901 patients covering 63 subtypes of rare tumor from cBioportal was obtained as the western cohort. Data of next generation sequencing (NGS) of 1312 patients from across China covering 67 subtypes was summarized as the Chinese cohort. Forty-one subtypes were overlapped between the two cohorts. The accumulative prevalence of TGAs was 20.40% (1000/4901) in cBioportal cohort, and 53.43% (701/1312) in Chinese cohort (p < 0.001). Among those 41 overlapping subtypes, it was still significantly higher in Chinese cohort compared with cBioportal cohort (54.1%% vs. 26.1%, p < 0.001). Generally, targetable mutations in BRAF, BRCA2, CDKN2A, EGFR, ERBB2, KIT, MET, NF1, ROS1 were ≥3 times more frequent in Chinese cohort compared with that of cBioportal cohort. Cancer of unknown primary tumor type, gastrointestinal stromal tumor, gallbladder cancer, intrahepatic cholangiocarcinoma, and sarcomatoid carcinoma of the lung were the top 5 tumor types with highest TGAs. Conclusions: The incidence of TGAs in rare tumors was substantially high worldwide and was even higher in Chinese rare tumor population. Comprehensive genomic profiling may offer novel treatment paradigms to address the limited options for patients with rare tumors.

Comprehensive Genomic Profiling of Central Giant Cell Lesions Identifies Clinically Relevant Genomic Alterations

2017 ◽  
Vol 75 (5) ◽  
pp. 955-961 ◽  
Author(s):  
Brett Bezak ◽  
Heidi Lehrke ◽  
Julia Elvin ◽  
Laurie Gay ◽  
David Schembri-Wismayer ◽  
...  
Keyword(s):  
Giant Cell ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Comprehensive Genomic Profiling

scholarly journals OA03.05 Characterization of Genomic Alterations in Chinese LCNEC and SCLC via Comprehensive Genomic Profiling

2019 ◽  
Vol 14 (10) ◽  
pp. S212-S213
Author(s):  
L. Wu ◽  
L. Cao ◽  
L. Chen ◽  
B. Zhu ◽  
X. Hu ◽  
...  
Keyword(s):  
Genomic Profiling ◽  
Genomic Alterations ◽  
Comprehensive Genomic Profiling

The impact of comprehensive genomic profiling in the management of patients with metastatic solid tumors in a developing country.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e18038-e18038
Author(s):  
Pablo M. Barrios ◽  
Marcio Debiasi ◽  
Carolina Cauduro ◽  
Fábio Herrmann ◽  
Gabriela Marchese ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Developing Country ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling ◽  
The Impact

Comprehensive genomic profiling of neuroendocrine carcinoma of the prostate.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 187-187
Author(s):  
Sumanta K. Pal ◽  
Matthew I. Milowsky ◽  
Julia Andrea Elvin ◽  
Siraj Mahamed Ali ◽  
Jean H. Hoffman-Censits ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Stage Iv ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Tumor Type ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Carcinoma Of The Prostate ◽  
Comprehensive Genomic Profiling ◽  
Metastatic Sites

187 Background: Neuroendocrine carcinoma of the prostate (NCAP) is an aggressive high grade malignancy that often presents as metastatic disease. Current treatments of this tumor have only modest benefit leading investigators to query whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 37 consecutive cases of relapsed/metastatic NCAP. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 583X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: The median age of the men in this study was 65.1 years (range 43 to 83 years). All (100%) cases were positive for neuroendocrine markers on immunohistochemical staining and were Stage IV at the time of CGP. Samples used for sequencing were obtained from the primary tumor in 9 (24%) of NCAP and from metastatic sites in 28 (76%) of NCAP (12 liver, 6 LN, 2 each from bladder, pelvis and soft tissue, and 1 each from rectum, bone, urethra and ureter. There were 213 total GA (5.8 GA/sample) and 47 CRGA (1.3 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (68%) and RB1 (51%). TMPRSS:ERG fusions were identified in 32% of cases whereas AR was altered in 8% (1 mutation and 2 amplifications). The most frequent CRGA involved PTEN (32%), BRCA2 (14%), FGFR1 (5%), PIK3CA (5%) and AKT2 (3%). No alterations in BRAF were identified. Clinical responses to MTOR inhibitors in patients with MTOR pathway alterations will be presented. Conclusions: NCAP has distinctive genomic alterations from classic acinar CAP including reduced frequencies of alterations in TMPRSS:ERG and AR and frequent RB1 mutations. Multiple alterations in the MTOR pathway identified in this infrequent tumor type suggest that these patients may be candidates for MTOR inhibitors and other targeted therapies.

Efficacy of systemic treatment for metastatic renal cell carcinoma (mRCC) guided by comprehensive genomic profiling (CGP).

2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 63-63
Author(s):  
Paulo Gustavo Bergerot ◽  
Cristiane Decat Bergerot ◽  
Nazli Dizman ◽  
Nicholas Salgia ◽  
Joann Hsu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clinical Care ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Comprehensive Genomic Profiling

63 Background: Comprehensive genomic profiling (CGP) has been used to guide treatment selection in metastatic renal cell carcinoma (mRCC). This study sought to determine if genomic alterations guided treatment and contributed to improved outcomes. Methods: From a single institution, patients (pts) diagnosed with mRCC who had CGP in the course of clinical care were identified. Pts were tested on a CLIAA-certified platform (FoundationOne; Cambridge, MA). Pts who died/initiated hospice within the 30 days after the test was performed or who were lost to follow-up were excluded. Duration of therapy (DOT) was measured as months between first and last day of therapy following CGP test. The Kaplan-Meier method was undertaken to estimate the association of CGP-directed therapy with overall survival (OS). Cox regression was also performed and adjusted for histologic subgroup. Results: A total of 64 patients underwent CGP between February 2014 and August 2018. From this group, 15 patients were excluded due to death/hospice within 30 d (n = 10) and lack of follow-up (n = 5). Median age at diagnosis was 60 years (range, 24-84), and 79% were male. Most patients (69%) were diagnosed with clear cell RCC. The median identified genomic alterations (GAs) was 3 (range, 0-7). The most common GAs were VHL (54%), PBRM1 (28%), TERT (21%), TP53 (15%), BAP1 (13%), and SETD2 (13%). Of the 49 patients included in this analysis, 47% had actionable mutations based on their CGP results. Of those, 13 patients received directed-therapy of whom 57% had stable disease, 28% had partial response, and 14% had progressive disease. The median time from CGP test to treatment was 1 month (range, 0-17). The median duration of directed-therapy was 12 months (range, 1-28) and of non-directed therapy was 4 months (range, 1-40) (P = 0.04). Directed-therapy was significantly associated with better OS (adjusted HR, 0.32 [95% CI, 0.13 to 0.82]; P = 0.018) compared to non-directed therapy. Conclusions: This study provides preliminary evidence to justify CGP-guided therapy in mRCC. Forthcoming studies should prospectively explore the use of CGP in treatment allocation for mRCC to validate these findings.

Cyclin pathway genomic alterations across 5,356 prostate cancers.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 179-179
Author(s):  
Denis Leonardo Fontes Jardim ◽  
Sherri Z. Millis ◽  
Michele Sue-Ann Woo ◽  
Jeffrey S. Ross ◽  
Siraj Mahamed Ali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Resistance Pathway ◽  
Lower Likelihood ◽  
Ccnd1 Amplification ◽  
Comprehensive Genomic Profiling ◽  
Prostate Cancers ◽  
Copy Number Changes ◽  
Generation Sequencing

179 Background: The cyclin pathway is comprised of possible targetable alterations as well as resistant alterations that affect treatment, including hormonal agents. We describe the landscape of cyclin genomic alterations in prostate cancer. Methods: Consecutive samples were analyzed in a CLIA-certified laboratory using comprehensive genomic profiling (CGP) performed by next-generation sequencing (315 genes, >500X coverage). We describe alterations in activating genes (Table) and co-alterations in resistant genes ( RB1 and CCNE1) (related to cyclin inhibition) and androgen receptor ( AR). Results: Alterations in any cyclin pathway genes were found in 9.7% of the 5,356 tumors analyzed. Frequent alterations included CCND1 amplification (4.2%) and CDKN2A and B loss (2.4% each). Frequencies were substantially different according to prostate cancer histology (Table). The majority of alterations were copy number changes. Alterations in possible resistance genes, RB1 and CCNE1 were detected in 9.7% (up to 54.6% in neuroendocrine) and 1.2% of cases, respectively, while AR alterations were seen in 20.9% (up to 27.3% in anaplastic). Co-occurrence analysis demonstrated a lower likelihood of concomitant vs. isolated alterations in cyclin activating and resistance pathway (odds ratio (OR), 0.44, p<0.001). Conversely, we detected a higher likelihood of co-occurrence between AR and cyclin alterations (OR 1.79, p<0.001). Conclusions: Cyclin pathway genomic abnormalities were observed in about 10% of prostate cancer tumors, and are more frequently associated with concomitant AR alterations and absence of co-alterations associated with resistance to cyclin inhibition.[Table: see text]

Comprehensive genomic profiling for chemotherapy-naïve advanced gastrointestinal malignancies.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 832-832
Author(s):  
Tomohiro Kondo ◽  
Quy Pham Nguyen ◽  
Junichi Matsubara ◽  
Keita Fukuyama ◽  
Motoo Nomura ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Gastrointestinal Malignancies ◽  
Tract Cancer ◽  
Novel Approach ◽  
Comprehensive Genomic Profiling ◽  
Novel Biomarkers ◽  
Effective Drugs ◽  
Clinical Trial Information

832 Background: From June, 2019, two comprehensive genomic profiling (CGP) assays, "FoundationOne CDx" and “OncoGuide NCC Oncopanel”, were reimbursed by the national insurance system in Japan for patients who were refractory to standard chemotherapy. However, their clinical utility for chemotherapy-naïve cancer patients is unknown. Methods: We conducted a single institutional prospective observational study to evaluate the clinical utility of FoundationOne CDx assay (Cambridge, MA, USA) for the patients with chemotherapy-naïve advanced gastrointestinal malignancies. Patients with adequate H.E. sample were registered in this study. Primary outcome was the detection rate of at least one actionable/druggable cancer genomic alterations. The evidence levels were classified according to clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (Edition 1.0) (Sunami K. Cancer Sci. 2018). Results: From October 2018 to June 2019, a total of 238 patients were screened and the following 158 patients were registered: colorectal cancer (n = 60), gastric cancer (n = 19), esophageal cancer (n = 23), pancreatic cancer (n = 30), biliary tract cancer (n = 11), rare gastrointestinal malignancies (n = 15). The CGP data were obtained for 113 patients . Median turn-around time was 14 days (range 10-247 days). Actionable/druggable cancer genomic alterations were observed in 113 patients (100%)/ 65 patients (57.5%), respectively. Clinically relevant biomarkers and genomic alterations were identified in 22 patients (19.5%); BRCA2 (n = 4), ERBB2 (n = 4) , BRAF (n = 3) , EGFR (n = 3), FGFR2 (n = 2), MET (n = 2), NTRK (n = 2) , MSI-H (n = 2 ), TMB-high (n = 2), ALK (n = 1) , KIT (n = 1) and ROS1 (n = 1). Of note, novel biomarkers such as ROS1- GOPC fusion and PALB2 rearrangement were obtained in the patients with esophageal squamous cell carcinoma. Conclusions: This is the first study to evaluate the clinical utility of CGP in patient with chemotherapy-naïve advanced gastrointestinal malignancies. Our result indicated that CGP might provide a chance of potentially effective drugs as a novel approach in precision cancer medicine. Clinical trial information: UMIN000034830.

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