Background

In the current treatment protocols, organ-preserving oncologic treatment is often advocated for patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) with surgery as a salvage option. After oncologic treatment, ie radiotherapy or chemoradiotherapy [(C)RT], accurate assessment of treatment response is essential.


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Early detection of residual disease is of utmost importance to recognize patients who will need salvage surgery. On the other hand, patients with complete response need to be identified to avoid unnecessary surgical or endoscopic procedures including tissue biopsies, which may carry an increased risk of complications in this patient group treated with (C)RT.1

Anatomical distortion caused by the tumor and therapy-induced changes in tissues make the evaluation of treatment response challenging for conventional anatomical imaging methods [computed tomography (CT), MRI], and thus, their accuracy in this setting has not been optimal.2,3 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, and recently, FDG-PET/CT imaging have been recommended for assessing treatment response after oncologic treatment of HNSCC. The diagnostic accuracy of FDG-PET or FDG-PET/CT is reportedly good in this setting.

Particularly, the negative predictive value (NPV) has been reported to be high. In two recent meta-analyses, the NPV was around 95% for both primary site and neck, provided that FDG-PET/CT was not performed earlier than 10–12 weeks after completion of (C)RT.4,5

According to the present guidelines at our institution, FDG-PET/CT is performed 12 weeks after completion of definitive (C)RT to assess treatment response. Patients with negative FDG-PET/CT and with no clinical suspicion of residual disease are regarded as having complete response and are only followed up clinically.

In cases with suspected residual disease in FDG-PET/CT and/or clinically, biopsies and/or salvage surgery is considered. To audit this FDG-PET/CT based protocol, we retrospectively analyzed the accuracy of FDG-PET/CT imaging in the assessment of treatment response after definitive (C)RT for HNSCC.

Patients and Methods

Institutional approval to conduct this retrospective study was obtained. We included all patients with FDG-PET/CT performed to assess treatment response after definitive (C)RT for previously untreated HNSCC at our institution during 2008–2010. The hospital records were reviewed and data on patient characteristics, treatment, FDG-PET/CT findings, histopathology, and follow-up were collected.

Patients with FDG-PET/CT performed earlier than 10 weeks or later than 18 weeks after completion of (C)RT were excluded. For patients with negative FDG-PET/CT scan and no proven recurrence (ie patients with FDG-PET/CT considered true negative), the follow-up time was calculated from the completion of (C)RT to the date of last visit or to the death.

The study period was chosen to ensure a sufficient sample size and an adequate follow-up time for the analysis. The diagnostic accuracy [NPV, positive predictive value (PPV), specificity, sensitivity, and accuracy] of FDG-PET/CT in detecting residual tumor was calculated generally and specifically for the primary site and neck. Histopathologic and clinical follow-up data served as the standard reference. When assessing the neck, only patients diagnosed with clinically N+ disease were taken into account.

Post-treatment histopathologic data as a reference standard were available for all patients who had had positive FDG-PET/CT or clinical suspicion of residual disease indicating a neck dissection and/or biopsies from the primary tumor area.

Patients with negative FDG-PET/CT and with no clinical suspicion of residual disease had only been followed up clinically, and they had follow-up data with possible later imaging and histopathology as a reference standard.

Oncologic Treatment

Of the 88 eligible patients, 12 (14%) were treated by radiotherapy only and 76 (86%) by (C)RT. Intensity modulated radiotherapy (IMRT) was used in 85 patients (97%), and three patients (3%) were treated by conventional 3-D radiotherapy.

In the patients treated by IMRT, the clinical target volume (CTV1) typically first included the gross tumor volume (GTV) with 1 cm margins and the elective nodal areas. A 3–5 mm margin was added to CTV1 to obtain the planning target volume (PTV1).

This volume was irradiated to a cumulative dose of 50 Gy in 2 Gy daily fractions in five weeks. The primary tumor area and areas with nodal metastasis (PTV2-3) were then irradiated up to a mean total dose of 69 Gy (range 58–72 Gy). Three patients with T2 laryngeal cancer were treated by conventional 3-D radiotherapy from wedged lateral laryngeal fields. The mean total treatment time was 51 days (range 37–84 days).

Most of the patients (= 63, 72%) treated by (C)RT were scheduled to receive cisplatin 40 mg/m2 weekly up to six cycles during the radiotherapy. Eight patients (9%) received weekly cetuximab during the radiotherapy course. Two patients with nasopharyngeal cancer were treated with cisplatin 100 mg/m2 at three-week intervals up to three times concurrently with radiotherapy. Weekly carboplatin, cisplatin together with panitumumab, and cisplatin combined with etoposide were used each in one patient.