Evaluation of microsatellite instability (MSI) status in 11,573 diverse solid tumors using comprehensive genomic profiling (CGP).

426 Background: UrthCa is an uncommon GU malignancy that can progress to advanced metastatic disease. Methods: 126 metastatic UrthCa underwent hybrid-capture based CGP to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: 49 (39%) urothelial (UrthUC), 31 (24%) squamous (UrthSCC), 34 (27%) adenocarcinomas (UrthAC) and 12 (9%) clear cell (UrthCC) were evaluated. UrthUC and UrthSCC were more common in men; UrthAC and UrthCC more common in women. Ages were similar in all groups. GA in PIK3CA were the most frequent potentially targetable GA; mTOR pathway GA in PTEN also identified. GA in other potentially targetable genes were also identified including ERBB2 (6% in UrthUC, 3% in UrthSCC and 12% in UrthAC), FGFR1-3 (3% in UrthSCC), BRAF (3% in UrthAC), PTCH1 (8% in UrthCC) and MET (8% in UrthCC). Possibly reflecting their higher GA/tumor status, potential for immunotherapy benefit associated with higher TMB and PD-L1 staining levels were seen in UrthUC and UrthSCC compared to UrthAC and UrthCC. MSI high status was absent throughout. Conclusions: CGP reveals GA that may be predictive of both targeted and immunotherapy benefit in patients with advanced UrthCa and that could potentially be used in future adjuvant, neoadjuvant and metastatic disease trials.[Table: see text]

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1834P Impact of comprehensive genomic profiling and molecular tumor board decision on clinical outcome of patients with solid tumors: A single center, retrospective analysis

Annals of Oncology ◽

10.1016/j.annonc.2021.08.722 ◽

2021 ◽

Vol 32 ◽

pp. S1240-S1241

Author(s):

S.V. Ludwig ◽

L. Schmid ◽

A. Kahraman ◽

M. Rechsteiner ◽

M. Zoche ◽

...

Keyword(s):

Clinical Outcome ◽

Retrospective Analysis ◽

Solid Tumors ◽

Tumor Board ◽

Genomic Profiling ◽

Single Center ◽

Comprehensive Genomic Profiling ◽

Molecular Tumor Board ◽

Board Decision

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Abstract 179: Comprehensive genomic profiling of solid tumors for key targeted and immuno-oncology biomarkers using Ion Torrent NGS technology on the Oncomine Comprehensive Assay Plus (OCA Plus)

10.1158/1538-7445.am2020-179 ◽

2020 ◽

Author(s):

Vinay Mittal ◽

Jennifer Kilzer ◽

Dinesh Cyanam ◽

Janice Au-Young ◽

Santhoshi Bandla ◽

...

Keyword(s):

Solid Tumors ◽

Genomic Profiling ◽

Ion Torrent ◽

Comprehensive Genomic Profiling

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13539 ◽

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.

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482O Clinical impact of a pre-screening system using comprehensive genomic profiling to guide phase I trial registry in patients with advanced solid tumors

Annals of Oncology ◽

10.1093/annonc/mdv533.01 ◽

2015 ◽

Vol 26 ◽

pp. ix148

Author(s):

H.S. Okuma ◽

Y. Tanabe ◽

H. Ichikawa ◽

T. Kohno ◽

H. Yoshida ◽

...

Keyword(s):

Phase I ◽

Solid Tumors ◽

Phase I Trial ◽

Clinical Impact ◽

Genomic Profiling ◽

Advanced Solid Tumors ◽

Screening System ◽

Trial Registry ◽

Comprehensive Genomic Profiling

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Comprehensive genomic profiling of 30,000 consecutive solid tumors

10.1101/2020.11.19.20233866 ◽

2020 ◽

Author(s):

Scott A. Tomlins ◽

Daniel H. Hovelson ◽

Jennifer M. Suga ◽

Daniel M. Anderson ◽

Han A. Koh ◽

...

Keyword(s):

Solid Tumors ◽

Real World ◽

Tumor Tissue ◽

Tissue Sample ◽

Treatment Selection ◽

Genomic Profiling ◽

Tissue Samples ◽

Comprehensive Genomic Profiling ◽

Prostate Carcinomas ◽

The Impact

AbstractPurposeTissue-based comprehensive genomic profiling (CGP) is increasingly utilized for treatment selection in patients with advanced solid tumors, however real-world tissue availability may limit widespread implementation. Here we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples.Patients and MethodPost-hoc, non-prespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex PCR based-CGP (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Tumor tissue sample characteristics and PCR-CGP performance were assessed across all tested tumor samples, including exception samples not meeting minimum input requirements (<20% tumor content [TC], <2mm2 tumor surface area [TSA], DNA or RNA yield <1ng/ul, or specimen age >5yrs). Tests reporting at least one prioritized alteration or meeting all sequencing QC metrics (and ≥20% TC) were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting at least one actionable/informative alteration or those meeting all sequencing QC metrics (and ≥20% TC) were considered actionable.ResultsPCR-CGP was attempted in 31,165 of 32,048 (97.2%) consecutively received solid tumor tissue samples. Among the 31,165 tested samples, 10.7% had low (<20%) tumor content (TC) and 58.4% were small (<25mm2 TSA), highlighting the challenging nature of samples received for CGP. Of the 31,101 samples evaluable for input requirements, 8,079 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.6% of exception samples. Importantly, 80.6% of 1,344 tested prostate carcinomas and 87.8% of 1,144 tested lung adenocarcinomas yielded results informing treatment selection.ConclusionMost real-world tumor tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for >94% of samples, potentially expanding the proportion of CGP-testable patients, and thus the impact of biomarker-guided targeted and immunotherapies.

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