Clinical Outcomes of Patients Receiving Integrated PET/CT-Guided Radiotherapy for Head and Neck Carcinoma

Purpose

We previously reported the advantages of ¹⁸F-fluorodeoxyglucose–positron emission tomography (PET) fused with CT for radiotherapy planning over CT alone in head and neck carcinoma (HNC). The purpose of this study was to evaluate clinical outcomes and the predictive value of PET for patients receiving PET/CT-guided definitive radiotherapy with or without chemotherapy.

Methods and Materials

From December 2002 to August 2006, 42 patients received PET/CT imaging as part of staging and radiotherapy planning. Clinical outcomes including locoregional recurrence, distant metastasis, death, and treatment-related toxicities were collected retrospectively and analyzed for disease-free and overall survival and cumulative incidence of recurrence.

Results

Median follow-up from initiation of treatment was 32 months. Overall survival and disease-free survival were 82.8% and 71.0%, respectively, at 2 years, and 74.1% and 66.9% at 3 years. Of the 42 patients, seven recurrences were identified (three LR, one DM, three both LR and DM). Mean time to recurrence was 9.4 months. Cumulative risk of recurrence was 18.7%. The maximum standard uptake volume (SUV) of primary tumor, adenopathy, or both on PET did not correlate with recurrence, with mean values of 12.0 for treatment failures vs. 11.7 for all patients. Toxicities identified in those patients receiving intensity modulated radiation therapy were also evaluated.

Conclusions

A high level of disease control combined with favorable toxicity profiles was achieved in a cohort of HNC patients receiving PET/CT fusion guided radiotherapy plus/minus chemotherapy. Maximum SUV of primary tumor and/or adenopathy was not predictive of risk of disease recurrence.

Introduction

Head and neck squamous cell carcinoma originating in the upper aerodigestive tract accounts for approximately 5% of malignancies worldwide. Traditionally, CT has been the imaging modality of choice in staging and radiotherapy (RT) planning for head and neck cancer (HNC). Accumulating evidence shows advantages of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) over CT and other imaging modalities for detection of primary tumor, involved lymph nodes, and distant metastatic disease 1, 2, 3, 4. Disadvantages of PET, however, include its often poor correlation to precise anatomic structures and the confounding effect of normal physiologic FDG accumulation in certain areas, such as uninvolved muscles, lymphoid tissue of Waldeyer's ring, vocal cords, and salivary glandular tissue. These limitations have been significantly reduced with the advent of integrated PET/CT, in which subsequent PET and CT scans are obtained on a hybrid scanner and then fused by specialized software. Integrated PET/CT has been shown to be effective in differentiating normal physiologic uptake from tumor and frequently results in changes in radiotherapy planning and patient management 5, 6, 7, 8, 9.

Integrated PET/CT has proven to be especially useful in the staging and radiation therapy planning of head and neck malignancies. Because of the close proximity of several critical structures in this region, accurate detail of tumor and normal anatomy is crucial to ensure delivery of adequate radiation doses to areas of disease, while sparing exposure to as much normal tissue as possible. Studies have shown that PET/CT imaging in RT planning results in significant changes in gross tumor volume (GTV) 10, 11, 12, 13, 14 and node volume 10, 11 and detects positive nodes undiagnosed on CT alone 10, 11, 12, 13, 14, 15, 16. One study (17) reported 97% accuracy in tumor delineation for PET/CT vs. 69% for CT and 40% for magnetic resonance imaging (MRI). PET/CT can also be useful in locating unknown primary tumors (18) and distant metastases 10, 13, 16, and it occasionally leads to the diagnosis of previously undiagnosed synchronous primary cancers 13, 14. Reports have suggested that both the sensitivity and specificity of PET/CT are superior to both CT 15, 19, 20 and PET 16, 20 alone. Two studies reported a decrease in the number of PET findings read as equivocal by 60% (16) and 53% (18), respectively. Finally, studies report that the results of PET/CT imaging result in changes in patient management in 12%–31% of cases 10, 13, 16, 17, 18, 21.

One important treatment goal in radiotherapy of HNC is to limit side effects caused by irradiation of normal structures adjacent to tumor. This has become increasingly successful with the advent of intensity-modulated radiotherapy (IMRT) in recent years 22, 23. IMRT permits a steeper dose gradient than traditional RT modalities, allowing clinicians to deliver higher doses of radiation to desired areas while sparing more sensitive neighboring structures. Combined with the advantages of PET/CT planning in determining extent of primary disease and nodal spread, IMRT provides excellent locoregional control with a lower toxicity profile 14, 24.

Most published reports, including those just cited, discuss the feasibility of PET/CT imaging as part of staging and radiation therapy planning for HNC, but there is little data regarding clinical outcomes for these patients. The purposes of this study were (1) to evaluate clinical outcomes including overall survival, disease-free survival, and incidence of recurrence in patients with HNC who received PET/CT-guided radiation therapy and (2) to determine the correlation of these outcomes to maximum standard uptake value (SUV) obtained on PET scan. A secondary aim was to examine the toxic effects reported by those patients receiving IMRT.