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Purpose: An ASCO provisional clinical opinion offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This provisional clinical opinion addresses the appropriate use of tumor genomic testing in patients with metastatic or advanced solid tumors., Clinical Context: An increasing number of therapies are approved to treat cancers harboring specific genomic biomarkers. However, there is a lack of clarity as to when tumor genomic sequencing should be ordered, what type of assays should be performed, and how to interpret the results for treatment selection., Provisional Clinical Opinion: Patients with metastatic or advanced cancer should undergo genomic sequencing in a certified laboratory if the presence of one or more specific genomic alterations has regulatory approval as biomarkers to guide the use of or exclusion from certain treatments for their disease. Multigene panel-based assays should be used if more than one biomarker-linked therapy is approved for the patient's disease. Site-agnostic approvals for any cancer with a high tumor mutation burden, mismatch repair deficiency, or neurotrophic tyrosine receptor kinase ( NTRK ) fusions provide a rationale for genomic testing for all solid tumors. Multigene testing may also assist in treatment selection by identifying additional targets when there are few or no genotype-based therapy approvals for the patient's disease. For treatment planning, the clinician should consider the functional impact of the targeted alteration and expected efficacy of genomic biomarker-linked options relative to other approved or investigational treatments.Additional information is available at www.asco.org/assays-and-predictive-markers-guidelines., Competing Interests: Debyani ChakravartyConsulting or Advisory Role: Medendi Medical Travel Jeffrey SklarStock and Other Ownership Interests: PrecipioResearch Funding: Jilin Zixin (Inst) Kathleen MooreHonoraria: Research To Practice, Prime Oncology, Physicans' Education Resource, Great Debates and UpdatesConsulting or Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, TESARO (Inst), VBL Therapeutics, Merck, Aravive, Eisai, Vavotar Life Sciences, Mersana (Inst), Myriad Genetics, Alkemeres (Inst), Blueprint Pharmacetuicals (Inst), GlaxoSmithKline/Tesaro (Inst), I-Mab (Inst), InxMed (Inst), Mereo BioPharma (Inst)Research Funding: PTC Therapeutics (Inst), Lilly (Inst), Merck (Inst), Tesaro (Inst), Genentech (Inst), Clovis Oncology (Inst), Lilly Foundation (Inst), Regeneron (Inst), Advaxis (Inst), Bristol Myers Squibb (Inst), Verastem (Inst), Novartis Pharmaceuticals UK Ltd (Inst), AstraZeneca (Inst), Agenus (Inst), Takeda (Inst), Forty Seven (Inst), Stem CentRx (Inst), Immunogen (Inst), Bayer (Inst), Novogen (Inst), AbbVie/Stemcentrx (Inst)Other Relationship: GOG Partners (Inst) Shridar GanesanEmployment: Merck (I)Stock and Other Ownership Interests: Ibris, Inspirata, Merck (I), SilageneConsulting or Advisory Role: Inspirata, Novartis, Roche, Foghorn Therapeutics, Foundation Medicine, Merck Sharp & Dohme, Silagene, EQRx, EMD Serono, KayoTheraResearch Funding: M2Gen (Inst)Patents, Royalties, Other Intellectual Property: I hold 2 patents for digital imaging that may be licensed to Ibris Inc and Inspirata IncOther Relationship: NIH/NCI Christine M. LovlyHonoraria: Takeda, Pfizer, Cepheid, Foundation Medicine, AstraZeneca, Blueprint Medicines, Lilly, Genentech, Syros Pharmaceuticals, Amgen, Roche, EMD Serono, Daiichi Sankyo/AstraZeneca, Puma BiotechnologyConsulting or Advisory Role: Novartis, Foundation Medicine, Pfizer, Takeda, Cepheid, AstraZeneca, Blueprint Medicines, Syros Pharmaceuticals, Genentech, Lilly, Amgen, EMD Serono, Daiichi Sankyo/AstraZeneca, Puma BiotechnologyResearch Funding: Novartis, Xcovery, AstraZeneca (Inst)Travel, Accommodations, Expenses: Pfizer, Takeda, Foundation Medicine, Novartis, Cepheid, Genentech Stacy W. GrayStock and Other Ownership Interests: Magenta Therapeutics (I)Honoraria: Triptych Health PartnersConsulting or Advisory Role: Magenta Therapeutics (I) Jimmy HwangConsulting or Advisory Role: Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Caris Centers of Excellence, Pfizer, QED Therapeutics, Deciphera, IncyteSpeakers' Bureau: Bristol Myers Squibb, Deciphera, IncyteResearch Funding: Caris Centers of Excellence (Inst), Boehringer Ingelheim (Inst) Christopher LieuConsulting or Advisory Role: Ipsen (Inst), HalioDx (Inst), Pfizer (Inst)Research Funding: Merck (Inst) Fabrice AndréStock and Other Ownership Interests: PegacsyResearch Funding: AstraZeneca (Inst), Novartis (Inst), Pfizer (Inst), Lilly (Inst), Roche (Inst), Daiichi (Inst)Travel, Accommodations, Expenses: Novartis, Roche, GlaxoSmithKline, AstraZeneca Nilofer AzadConsulting or Advisory Role: AMAG Pharmaceuticals, Taiho Pharmaceutical, QED Therapeutics, Merck, Incyte, Helsinn Therapeutics/QED TherapeuticsResearch Funding: Celgene (Inst), Genentech (Inst), Astex Pharmaceuticals (Inst), Agios (Inst), Merck (Inst), Bristol Myers Squibb (Inst), Syndax (Inst), Array BioPharma (Inst), Intensity Therapeutics (Inst), Bayer (Inst), EMD Serono, Debiopharm Group (Inst), Incyte (Inst), Loxo/Lilly (Inst), AtlasMedx (Inst) Mitesh BoradStock and Other Ownership Interests: Gilead Sciences, AVEO, Intercept Pharmaceuticals, Spectrum PharmaceuticalsConsulting or Advisory Role: G1 Therapeutics, Fujifilm (Inst), Agios (Inst), Insys Therapeutics (Inst), Novartis (Inst), ArQule (Inst), Celgene (Inst), Inspyr Therapeutics, Halozyme (Inst), Pieris Pharmaceuticals (Inst), Taiho Pharmaceutical (Inst), Immunovative Therapies, Exelixis, Lynx Group, Genentech, Western Oncolytics, Klus Pharma, De Novo Pharmaceuticals, Merck, ImvaxResearch Funding: Boston Biomedical (Inst), miRNA Therapeutics (Inst), Senhwa Biosciences (Inst), MedImmune (Inst), BiolineRx (Inst), Agios (Inst), Halozyme (Inst), Celgene (Inst), Threshold Pharmaceuticals (Inst), Toray Industries (Inst), Dicerna (Inst), Sillajen (Inst), Eisai (Inst), Taiho Pharmaceutical (Inst), EMD Serono (Inst), Isis Pharmaceuticals (Inst), Incyte (Inst), Sun Biopharma (Inst), ARIAD (Inst), ImClone Systems (Inst), QED Therapeutics (Inst), Incyte (Inst), Puma Biotechnology (Inst), Adaptimmune (Inst), Merck Serono (Inst), RedHill Biopharma (Inst), Basilea (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: ArQule, Celgene, AstraZeneca Laura TafeStock and Other Ownership Interests: Exact Sciences, GlaxoSmithKlineResearch Funding: Biocartis (Inst)Other Relationship: College of American Pathologists, Association for Molecular Pathology Mark RobsonConsulting or Advisory Role: Change HealthCareResearch Funding: AstraZeneca (Inst), Pfizer (Inst), Merck (Inst)Other Relationship: Research to Practice, Clinical Care Options, Physicans' Education Resource, Pfizer, MyMedEd, Clinical Education AllianceUncompensated Relationships: Merck, Pfizer, Daiichi Sankyo, Epic Sciences, Artios, Tempus, Zenith PharmaOpen Payments Link: https://openpaymentsdata.cms.gov/physician/612669/summary Funda Meric-BernstamEmployment: MD Anderson Cancer CenterHonoraria: Rutgers Cancer Institute of New JerseyConsulting or Advisory Role: Samsung Bioepis, Xencor, Debiopharm Group, Silverback Therapeutics, IBM Watson Health, Roche, PACT Pharma, eFFECTOR Therapeutics, Kolon Life Sciences, Tyra Biosciences, Zymeworks, Puma Biotechnology, Zentalis, Alkermes, Infinity Pharmaceuticals, AbbVie, Black Diamond Therapeutics, Eisai, OnCusp Therapeutics, Lengo Therapeutics, Tallac Therapeutics, Karyopharm Therapeutics, BiovicaSpeakers' Bureau: Chugai PharmaResearch Funding: Novartis (Inst), AstraZeneca (Inst), Taiho Pharmaceutical (Inst), Genentech (Inst), Calithera Biosciences (Inst), Debiopharm Group (Inst), Bayer (Inst), Aileron Therapeutics (Inst), PUMA Biotechnology (Inst), CytomX Therapeutics (Inst), Jounce Therapeutics (Inst), Zymeworks (Inst), Curis (Inst), Pfizer (Inst), eFFECTOR Therapeutics (Inst), AbbVie (Inst), Boehringer Ingelheim (I), Guardant Health (Inst), Daiichi Sankyo (Inst), GlaxoSmithKline (Inst), Seattle Genetics (Inst), Taiho Pharmaceutical (Inst), Klus Pharma (Inst), Takeda (Inst)Travel, Accommodations, Expenses: Beth Israel Deaconess Medical CenterNo other potential conflicts of interest were reported.

ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody molecule labeled with IRDye 800CW, has been used in three Phase 0 microdosing clinical trials for fluorescence guided surgery. In May of 2019, the clinical trials were put on hold because the ABY-029 produced under Good Manufacturing Practices (GMP) for human administration had come to the end of term in which the drug product was known to be stable. Stability testing was halted due to limitations in supply of a suitable reference standard and a required test product being discontinued from commercial sale. In order to complete the remaining patients in the three clinical trials, new stability tests were developed and the GMP batch of ABY-029 drug product tested under the new protocols. The GMP batch of ABY-029 passed all stability tests under the new protocols and the Federal Drug Administration (FDA) has given permission to complete the remaining patients with stability testing of ABY-029 performed for each patient. The tests developed and used to test ABY-029 drug product stability are described here.

Background: Primary Ewing's sarcoma (ES) is typically seen within the long bones, vertebrae, or pelvis. Uncommonly, it can be found within the cranium among the rarest locations for primary ES are the skull base, in particular, the petroclival bone., Case Description: The patient is a 68-year-old female with past medical history of Stage III breast cancer who presented with severe retro-orbital headache and diplopia due to a cranial nerve VI palsy. Magnetic resonance imaging (MRI) revealed a mass at the left petroclival bone with extension into the adjacent left petrous apex and into the posterior aspect of the left cavernous sinus proximal to the carotid artery. The patient subsequently underwent an endoscopic transsphenoidal biopsy. Pathological and molecular analysis supported a diagnosis of ES. The patient then underwent neoadjuvant chemotherapy and radiotherapy. At 12 month-follow-up, her petroclival ES demonstrated significant interval decrease in size on MRI surveillance imaging., Conclusions: This is the third case of primary ES of the petroclival bone to be reported in the literature. In this patient, management consisted of surgical incisional biopsy followed by adjuvant radiation and chemotherapy. Knowledge and awareness of this type of tumor is important for the skull base surgeon., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Objective: The BRAF V600E mutation has been associated with aggressive disease in papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a useful adjunct to cytology in the diagnosis of malignancy and for tailoring clinical management. The aims of our study were to evaluate the BRAF mutational status using archived fine-needle aspiration biopsy (FNAB) material from patients with long-term follow-up and to correlate it with the original cytology diagnosis, clinicopathological stage at surgery, and prognosis., Study Design: FNAB material from 52 cases of PTC, with a mean follow-up of 8.4 years, was used in this study. DNA was extracted from archival cytology slides. Mutation analysis was performed by standard sequencing and locked nucleic acid-PCR/sequencing., Results: The BRAF V600E mutation was present in 46% of cases, but it was absent in all FNABs diagnosed originally as atypical and in 14 of 17 suspicious cases. Recurrence was significantly more frequent (p = 0.006) in cases with BRAF mutations and 54% of these cases presented with stage 2 or higher., Conclusion: The BRAF V600E mutation is associated with a higher pathological stage at surgery and a higher rate of recurrence. BRAF mutation analysis did not provide a significant increase in the accuracy of thyroid FNABs diagnosed as suspicious or atypical in our institution., (Copyright © 2011 S. Karger AG, Basel.)