tirapazamine and Oropharyngeal-Neoplasms

To compare nodal response rates following chemoradiotherapy in patients with p16+ and p16- oropharyngeal squamous cell carcinoma (OPSCC).. Patients with node-positive OPSCC treated at Peter MacCallum Cancer Centre on the published phase I-III tirapazamine trials were identified. All patients had conventional assessment (clinical examination (CA), CT and/or MRI) and positron emission tomography (PET) at both baseline and 2-4 months post-treatment.. There were 30 p16+ and 18 p16- patients, the former group having significantly higher stage nodal disease (P = 0.016). The mean overall reduction in nodal size at post-treatment assessment was similar in p16+ and p16- patients (78% vs. 75%), and no statistically significant difference in nodal complete response (CR) rates was detected by either CA (50% vs. 39%, P = 0.35) or PET/PET-CT (93% vs. 83%, P = 0.19). PET was significantly more accurate in determining the true nodal CR rate in both groups, with a negative predictive value of 96%.. Nodal response rates following chemoradiotherapy appear to be similar in p16+ and p16- patients when assessed by either CA or PET/PET-CT. However, higher nodal CR was seen in PET/PET-CT compared with CA in both groups. Metabolic imaging is more accurate than CA in assessing nodal response post-treatment.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chemoradiotherapy; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Male; Middle Aged; Neoplasm Proteins; Oropharyngeal Neoplasms; Radiation-Sensitizing Agents; Tirapazamine; Treatment Outcome; Triazines

To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial.. Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction.. Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13).. HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Australia; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Cyclin-Dependent Kinase Inhibitor p16; Disease-Free Survival; DNA, Viral; Europe; Female; Humans; Immunohistochemistry; In Situ Hybridization; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; New Zealand; North America; Oropharyngeal Neoplasms; Papillomaviridae; Polymerase Chain Reaction; Proportional Hazards Models; Radiotherapy, Adjuvant; Risk Assessment; Risk Factors; South America; Time Factors; Tirapazamine; Treatment Outcome; Triazines

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Hypoxia; Chemotherapy, Adjuvant; Cisplatin; Cyclin-Dependent Kinase Inhibitor p16; Disease-Free Survival; DNA, Viral; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomaviridae; Radiotherapy, Adjuvant; Risk Assessment; Risk Factors; Time Factors; Tirapazamine; Treatment Outcome; Triazines