Abstract
The aim of this study was to determine whether l -methyl-[ 11 C]-methionine (MET) positron emission tomography (PET) allows the prediction of outcomes in patients with head and neck mucosal malignant melanoma treated with carbon ion radiation therapy (CIRT). This was a retrospective cohort study involving 85 patients who underwent a MET-PET or MET-PET/computed tomography (CT) examination before and after CIRT. MET uptake in the tumour was evaluated semi-quantitatively using the tumour-to-normal tissue ratio (TNR). Local recurrence, metastasis, and outcome predictions were studied in terms of TNR before CIRT (TNRpre), TNR after CIRT (TNRpost), and the TNR change ratio. Kaplan–Meier curves revealed significant differences between patients with higher TNRpre values and those with lower TNRpre values in regard to local recurrence, metastasis, and outcome (log-rank test P < 0.0001 for all three). There were also significant differences in metastasis rates and outcomes between patients with higher and lower TNRpost values (log-rank test P = 0.0105 and P = 0.027, respectively). The Cox proportional hazards model revealed TNRpre to be a factor significantly influencing the risk of local recurrence (hazard ratio (HR) 29.0, P < 0.001), risk of metastasis (HR 2.67, P = 0.024), and the outcome (HR 6.3, P < 0.001). MET-PET or MET-PET/CT is useful for predicting the outcomes of patients with head and neck mucosal malignant melanoma treated with CIRT.
Malignant melanoma involves the skin in about 90% of all cases, whereas head and neck mucosal malignant melanoma is rare, accounting for less than 1% . Mucosal malignant melanoma is highly malignant, frequently showing lymphogenous or haematogenous metastasis. In cases with mucosal malignant melanoma, the head and neck region is often the site of involvement. Multimodality treatments comprising surgery, chemotherapy, and immunotherapy are used, but satisfactory outcomes have not as yet been obtained. Carbon ion radiotherapy (CIRT), which was introduced at the authors’ institution in 1994, has been used for the treatment of over 6500 patients to date. Patients who wish to receive CIRT come to this institution from all over Japan, as well as from other countries. Between 1997 and 2010, mucosal malignant melanoma was treated with CIRT in 198 patients, and the treatment outcomes were comparable to those of surgery .
Carbon ion radiotherapy
The carbon ion beam is a high linear energy transfer (LET) beam, the same as neutron and alpha rays. In comparison with low LET beams such as X-rays and proton beams, the carbon ion beam is characterized by the following features: (1) relative biological effectiveness is high, (2) the need for recovery from sub-lethal damage, a characteristic feature of high LET beams, is minimal , (3) cell cycle-related differences in sensitivity are small , and (4) the oxygen concentration-related difference is small (low oxygen enhancement ratio) . The carbon ion beam shows enhancement of the relative dose, which is called the Bragg peak, at a depth of approximately 15 cm from the body surface, whereas the relative dose is low in shallower parts. Because of these features, CIRT is considered to be an effective treatment for cancers that are resistant to conventional radiation therapy.
l -Methyl-[ 11 C]-methionine (MET)
Amino acid metabolism in cancer is involved in various catabolic processes related to tumour growth . MET is a neutral essential amino acid that plays a central role in the metabolism of cancer cells . MET is an amino acid necessary for cancer cells to perform protein and polyamine synthesis and transmethylation. Enhancement of these reactions facilitates amino acid uptake by cancer cells . Such metabolic processes can be evaluated by positron emission tomography (PET) using radiolabelled MET. Because the half-life of carbon-11 is as short as 20 min, MET imaging is feasible only at institutions that have cyclotron and radiochemistry facilities. According to past studies comparing MET-PET and 18 F-fluorodeoxyglucose (FDG)-PET in the treatment of skull base tumours , MET is more useful because it accumulates in the tumour to a greater extent than FDG. The precision for differentiating recurrent glioma from radiation necrosis is also higher with MET than with FDG or 11 C-choline . MET-PET is thus very useful for evaluating the efficacy of radiation therapy.
Carbon ion radiotherapy and PET for head and neck cancers
The protocol used for CIRT has been described in detail in a previous report . With regard to the therapeutic outcomes of patients with head and neck malignant melanoma treated with CIRT, the 5-year local control rate has been reported as 75%, and the 5-year cumulative survival rate as 35% . The therapeutic efficacy of CIRT using MET-PET and the usefulness of MET-PET in CIRT for head and neck adenocarcinoma and adenoid cystic carcinoma has been investigated previously by the present authors’ study team . The purpose of this retrospective study was to investigate the usefulness of MET-PET for predicting the therapeutic efficacy of CIRT in patients with head and neck mucosal malignant melanoma.
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