Advantage of FMISO-PET over FDG- PET for Predicting Histological Response to Preoperative Chemotherapy in Patients with Oral Squamous Cell Carcinoma

Jun Sato PhD, Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan
Yoshimasa Kitagawa PhD, Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan
Yutaka Yamazaki PhD, Department of Gerodontology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan
Hironobu Hata PhD, Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan
Takuya Asaka PhD, Oral Diagnosis and Medicine, Department of Oral Pathobiological Science,, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan
Masaaki Miyakoshi PhD, Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan
Masanobu Shindoh PhD, Oral Pathology and Biology, Department of Oral Pathobiological Science, Hokkaido University, Sapporo, Japan
Hypoxia is rare in normal tissues, but is common in cancers and is a prognostic factor for many types of cancer. In particular, hypoxia is a negative factor in the treatment of head and neck cancers, reducing the chance of cure. Hypoxia can be detected by 18F-Fluoromisonidazole (FMISO) positron emission tomography (PET). It is unclear whether hypoxia reflects the response to preoperative chemotherapy in patients with oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET with histological response to preoperative chemotherapy were therefore assessed in patients with OSCC.

This study enrolled 22 patients with OSCC (14 men, 8 women; median age 65 yrs; range, 42-86 yrs) undergoing preoperative chemotherapy between 2009 abd 2013. The T-stages were T2 in 6 patients, T3 in 3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5. All of the patients received preoperative chemotherapy with oral anticancer agent. Two received oral tegafur-uracil (UFT; Taiho Pharmaceutical Co., Ltd, Tokyo, Japan), 18 received oral tegafur-gimeracil-oteracil-potassium (S-1; Taiho Pharmaceutical Co., Ltd, Tokyo, Japan), and 2 received both agents.  The median duration of chemotherapy was 14 days (range:, 6-31 days). This study was approved by the Institutional Ethics Committee in our institution (2009).

Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the maximum standardized uptake value (SUVmax) of FDG- and FMISO-PET and tumor-muscle-ratio (TMR) of FMISO-PET were measured. The threshold for hypoxic volume based on FMISO TMR was set at 1.25. The histological response to preoperative chemotherapy was evaluated using operative materials. Chi-square test and logistic regression analysis were used to compare histological response to preoperative chemotherapy and PET uptake or other factors

FMISO-PET and FDG-PET detected uptake by primary OSCCs in 15 (68%) and 21 (95%) patients, respectively, with median SUVmax’s of FMISO- and FDG-PET in the primary site were 2.0 (range, 1.3-3.5) and 16.0 (range, 1.0-32.2), respectively. The median of FMISO TMR was 1.5 (range, 0.99-2.96). There were 5 cases whose FMISO TMR was less than 1.25. Histological evaluation showed good response to preoperative chemotherapy in 7 patients (32%) and poor response in 15 (68%). Good response was significantly more prevalent in patients with negative than positive for FMISO uptake (P < 0.001) and without hypoxic area evaluated by FMISO-PET TMR (P=0.04), whereas FDG uptake was not significantly correlated with response to chemotherapy response. Multivariate logistic regression analysis showed that FMISO uptake was an independent significant predictor of response to preoperative chemotherapy (P = 0.03, odds ratio=0.06, 95% confidence interval=0.004-0.759).

In conclusion, the advantage of FMISO-PET over FDG- PET for predicting histological response to preoperative chemotherapy in patients with OSCC was observed.

References:

  1. Okamoto S, Shiga T, Yasuda K, Ito YM, Magota K, Kasai K. Kuge Y, Shirato H, Tamaki N. High reproducibility of tumor hypoxia evaluated by 18 F-Fluoromisonidazole PET for head and neck cancer. J Nucl Med 2013;54:201-7.

  2.  Sato J, Kitagawa Y, Yamazaki Y, Hata H, OkamotoS, Shiga T, Shindoh M, Kuge Y, Tamaki N. FMISO-PET uptake is correlated with HIF-1α expression in oral squamous cell carcinoma. J Nucl Med. 2013; 54: 1060-5.

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