Feasibility of Targeting PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma.
PIK3CA is the only frequently-mutated, directly druggable oncogene in head and neck squamous cell carcinoma (HNSCC). However, it is unclear if a molecularly-driven intervention trial can be launched successfully, particularly within a single-institution setting secondary to the infrastructure necessary for mutation detection, mutation prevalence, and patient willingness to participate. This study aimed to evaluate 1) local frequency of PIK3CA activating mutations in HNSCC, 2) timeliness of our mutation-profiling clinical pathway, and 3) patients' willingness to enroll in a novel neoadjuvant drug trial. Tissue biopsies of 25 consecutive cases of HNSCC were tested for activating PIK3CA mutations at three mutational hotspots by real-time polymerase chain reaction. Mutations prevalence and number of working days accrued in determining PIK3CA mutational status were calculated. In addition, 30 HNSCC patients were surveyed prospectively regarding their willingness to participate in a hypothetical drug trial. Survey data were summarized descriptively. 4 of 25 (16 %) tumors harbored a PIK3CA activating mutation, including one at codon E542K, two at codon E545K/D, and one at codon H1047R. On average, this result was obtained in approximately 15 working days (range, 9-24 working days). The majority of patients surveyed (70 %) indicated their willingness to participate in a targeted PIK3CA trial. This study provides evidence that within a single institution, PIK3CA activating mutations can be detected with expected frequency, with sufficient timeliness and sufficient patient interest to mount a targeted intervention trial that may lead to improved tumor response in selected HNSCC patients.
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada. jtheurer@uwo.ca.|School of Communication Sciences and Disorders, Faculty of Health Sciences, Western University, Elborn College, London, ON, N6G 1H1, Canada. jtheurer@uwo.ca.|Lawson Health Research Institute, 750 Base Line Rd., London, ON, N6C 2R5, Canada. jtheurer@uwo.ca.|Department of Otolaryngology - Head and Neck Surgery, London Health Sciences Centre - Victoria Hospital, Rm B3-451, 800 Commissioners Rd E., London, ON, N6A 5W9, Canada. jtheurer@uwo.ca.
Julie A
JA
Theurer
Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, Dental Sciences Building, London, ON, N6A 5C1, Canada.
William
W
Stecho
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
John
J
Yoo
Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, Dental Sciences Building, London, ON, N6A 5C1, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Keith
K
Kwan
Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, Dental Sciences Building, London, ON, N6A 5C1, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Bret
B
Wehrli
Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, Dental Sciences Building, London, ON, N6A 5C1, Canada.
Vimla
V
Harry
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Morgan
M
Black
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Nicole
N
Pinto
Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Eric
E
Winquist
Lawson Health Research Institute, 750 Base Line Rd., London, ON, N6C 2R5, Canada.|Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
David
D
Palma
Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Suzanne
S
Richter
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|Lawson Health Research Institute, 750 Base Line Rd., London, ON, N6C 2R5, Canada.|Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
John W
JW
Barrett
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
S
S
Danielle MacNeil
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Kevin
K
Fung
Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, Dental Sciences Building, London, ON, N6A 5C1, Canada.
Christopher J
CJ
Howlett
Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|Lawson Health Research Institute, 750 Base Line Rd., London, ON, N6C 2R5, Canada.|Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada.|London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada.
Anthony C
AC
Nichols
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C484760:PIK3CA protein, human
Biomarkers; Feasibility study; Head and neck squamous cell carcinoma; PIK3CA; Targeted therapeutics