2.3. Treatment protocol

As a rotating gantry for irradiating pancreatic cancers was not available at our institute in 2016 [16], all patients were immobilised in the supine and/or prone positions in customised cradles (Moldcare; Alcare, Tokyo, Japan) using thermoplastic shells (Shellfitter; Kuraray, Osaka, Japan). A respiratory gating system using pressure monitoring under thermoplastic shell was used for conducting planning computed tomography (CT) and for delivering C-ion RT. The peak exhalation ±10% respiratory phase was used for both planning CT and treatment execution to mitigate the respiratory movement of the tumour and surrounding organs. Non-contrast CT images with a slice thickness of 2 mm were obtained for treatment planning. Planning CT images were fused with those obtained using contrast-enhanced CT, gadolinium-enhanced magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for accurate gross tumour volume (GTV) delineation. The clinical target volume (CTV) was defined as the GTV plus a 0–5 mm margin and was reduced in size if it lay close to the gastrointestinal tract. The PTV was defined as the CTV plus a 5-mm margin to account for set-up errors. The goals for target volume coverage were that 95% of the GTV and 90% of the PTV should be covered by 95% of the prescribed dose. All doses of initial and repeat C-ion RT were both administered in 12 fractions by passive beam, 4 times a week for 3 weeks.

We followed our institutional protocol concerning dose constraints to the organs at risk. The total dose of the initial and repeat C-ion RT to the gastrointestinal tract covering 2 cc (D2cc) was ≤60 Gy (RBE), while that to the spinal cord was ≤40 Gy (RBE). Three-dimensional treatment planning was performed using the in-house HIPLAN (NIRS, Chiba, Japan) and Xio-N (ELEKTA, Stockholm, Sweden; Mitsubishi Electric, Tokyo, Japan) planning software. To reduce the gastrointestinal and spinal doses, personalised separate angles including a beam originating from the oblique dorsal side were used. Biological treatment plan optimisation that took into account a clinical RBE value of 3 at the distal part of the Bragg peak was used. A representative case is shown in Fig. 1.

A representative patient with pancreatic body cancer. The initial carbon-ion radiotherapy (C-ion RT) was 50.4 Gy (RBE)/12 fraction/3 weeks. Moreover, gemcitabine was administered as bridging and concurrent chemotherapy. The patient developed in-field local failure 13 months after initial C-ion RT. S-1 was delivered as bridging chemotherapy, and re-irradiation with 55.2 Gy (RBE)/12 fraction/3 weeks was delivered 17 months after the initial C-ion RT. The patient received a third round of C-ion RT following marginal recurrence at the site of initial C-ion RT 29 months after that initial treatment. Furthermore, the patient received intensity-modulated radiotherapy for recurrence at the para-aortic lymph node more than 5 years after the initial C-ion RT. However, the patient developed septic shock for unknown reasons and died 75 months after the initial C-ion RT. (A) An 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) image of the pancreas before initial C-ion RT. (B) Dose distribution of the initial C-ion RT. (C) An 18F-FDG-PET image showing in-field local failure. (D) Dose distribution for re-irradiation.

With respect to chemotherapy, 10 patients received concurrent chemotherapy with intravenous gemcitabine 1000 mg/m² on days 1, 8, and 15. Three patients received S-1 (a combination of tegafur, gimeracil, and oteracil) 80 mg/m² twice daily for 2 weeks, followed by 1 week of rest as one course. There were 13 and 10 patients who received induction chemotherapy and adjuvant chemotherapy, respectively.