PURPOSE Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( P = .04). For IMRT, 2-year PFS was 87.6% ( P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( P = .56). CONCLUSION The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

18 F-FDG metabolic tumor volume (MTV) and total glycolytic activity (TGA) have been proposed as potential prognostic imaging markers for patient outcome in human solid tumors. The purpose of this study was to establish whether MTV and TGA add prognostic information to clinical staging in patients with oral and oropharyngeal squamous cell carcinomas (SCCs). Methods: The Institutional Review Board approved this Health Insurance Portability and Accountability Act-compliant singleinstitution retrospective study. Forty-five patients with histologically proven oral or oropharyngeal SCC underwent PET/CT for initial cancer staging and were included in the study. MTV was measured using a gradient-based method (PET Edge) and fixed-threshold methods at 38%, 50%, and 60% of maximum standardized uptake value (SUV). The TGA is defined as MTV · mean SUV. Bland-Altman analysis was used to establish the reliability of the methods of segmentation. Outcome endpoints were overall survival (OS) and progression-free survival. Cox proportional hazards univariate and multivariate regression analyses were performed. Results: In Cox regression models, MTV and TGA were the only factors significantly associated with survival outcome after adjusting for all other covariates including American Joint Committee on Cancer (AJCC) stage, with hazards ratio of 1.06 (95% confidence interval, 1.01-1.10; P 5 0.006) and 1.00 (95% confidence interval, 1.00-1.01; P 5 0.02). The model fit was significantly better when MTV was added to AJCC stage in model I (x 2 value change, 1.16-6.71; P 5 0.01) and when TGA was added to AJCC stage in model II (x 2 value change, 1.16-4.37; P 5 0.04). The median cutoff point of 7.7 mL for primary tumor MTV was predictive of time to OS (log rank P 5 0.04). The median cutoff point of 55 g for PET Edge primary tumor TGA was predictive of time to OS (log rank P 5 0.08), though the result was not statistically significant. Conclusion: Gradient-based segmentations of primary tumor MTV and TGA are potential 18 F-FDG markers for time to survival in patients with oral and oropharyngeal SCC and may provide prognostic information in addition to AJCC stage. These exploratory imaging markers need validation in larger cohort studies.

In patients with head and neck cancer, posttreatment imaging can be complicated and difficult to interpret because of the complexity of the surgical procedures performed and the postirradiation changes, but such imaging is critical for the evaluation of (a) the response to therapy and (b) tumor control. Posttreatment changes are affected by the type of surgery performed, reconstruction, neck dissection, and radiation therapy. Three types of flaps are used for reconstruction in the head and neck region: (a) the local flap, with geometric repositioning of adjacent tissue; (b) the pedicle flap, with rotation of donor tissue and preservation of the original vascular system; and (c) the free flap, with transfer of tissue that is revascularized by using microvascular surgical techniques. The posttreatment imaging findings in patients with head and neck cancer can be divided into four groups: altered anatomy secondary to surgical reconstruction, tumor recurrence, potential postsurgical complications, and possible postirradiation changes. Potential postsurgical complications are wound infection, abscess, fistula, flap necrosis, hematoma, chylous fistula, and serous retention. Possible postirradiation changes include mucosal necrosis, osteoradionecrosis, radiation-induced vasculopathy, radiation pneumonitis, radiation lung fibrosis, radiation-induced brain necrosis, and radiation-induced secondary malignancies. A familiarity with the imaging characteristics of posttreatment changes and of the potential complications caused by surgery and irradiation and an ability to differentiate these findings from tumor recurrence are essential for posttreatment surveillance and follow-up management of patients with head and neck cancer.

FDG PET metabolic tumor volume estimated using gradient segmentation had superior correlation and reliability with the estimated ellipsoid pathologic volume of the tumors compared with threshold method segmentation.

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