Necrosulfonamide br Methods and materials br Patients br

Methods and materials
Patients
A total of 42 unresectable LAPC patients treated with CCRT using proton beams at our institute between July 2009 and March 2016 were retrospectively reviewed. This study included 21 men and 21 women, whose age ranged from 39 to 83 (median: 66) years. Computed tomography (CT) or magnetic resonance imaging (MRI) with Necrosulfonamide agents was performed for staging prior to PBT in all patients. Re-evaluation in our institute was performed for 32 patients who had already received chemotherapy at their initial hospital. Clinical staging of IIB/III was 1/41 according to the Union for International Cancer Control (UICC) TNM staging system (7th edition). Regional lymph nodes were defined in accordance with the UICC system as superior and inferior to the head and body of the pancreas, anterior pancreaticoduodenal, posterior pancreatico-duodenal, common bile duct, and proximal mesenteric lymph nodes. Pyloric and celiac lymph nodes were included for head of pancreatic tumors, and the hilum of the spleen and the tail of the pancreatic lymph nodes were included for body and tail of it. ‘‘Unresectable” was defined as tumors involving more than 180 degree of celiac artery (CA) or superior mesenteric artery (SMA) on CT scan. A total of 32 patients had already received chemother-apy at their initial hospital before they came to our institute (Table 1). Pre-treatment chemotherapy outside of our center in 32 patients was done at their previous physician’s discretion and included GEM, S-1, FOLFOX, nab-PTX and combinations.
All procedures involving human participants, including case reviews of treatments, were conducted in accordance with the eth-ical standards of the 1964 Helsinki declaration and its later amend-ments (or comparable ethical standards) and approved by the University of Tsukuba Institutional Research Committee (Approval # H29-080). All treatments were discussed at an in-hospital con-ference and informed consent was obtained from all participants included in the study. We got informed consent from either living patients or the legally designated next-of-kin for those who died, as appropriate.
Proton beam therapy
Before making a treatment plan, CT images without intravenous contrast agent were taken at 2.5 mm intervals during the expira-
Table 1
Patients’ characteristics.
Number of patients 42
Age
Stage (IIB/III)
Pre-treatment (chemotherapy) 32
Concurrent
Chemotherapy + hyperthermia 23
Post treatment (chemotherapy/surgery) 34/2
The number inside the brackets means median value.
Abbreviations: GEM: Gemcitabine, S-1: Tegafur/Gimeracil/Oteracil, GyE: gray equivalent. 
tory phase under a respiratory gating system [15]. We defined the gross tumor volume as primary tumor and metastatic regional lymph nodes. The clinical target volume (CTV) was judged to be an approximately 5 mm margin around the gross tumor volume and the roots of celiac or superior mesenteric arteries (CA, SMA) were involved in cases of lesions which had invaded around the vessels. Regional but non-metastatic regional lymph nodes were not included in the CTV. The stomach, duodenum and intestine were counted as GI tract for our purposes. Beam-dependent margins were directly added to the CTV, such as a 1 cm margin around the CTV, and a 5-mm margin was added to the caudal direction to compensate for unexpected respiration-induced movements. Total irradiation doses were 50 Gray equivalents (GyE) with 25 fractions in 12 cases, 54 GyE in 27 fractions in 2 cases, 56 GyE in 28 fractions in 4 cases, 59.4 GyE in 33 fractions in 1 case, 60 GyE in 30 fractions in 6 cases, and 67.5 GyE in 25 fractions (concomi-tant boost technique) in 17 cases. The protocol was decided by irra-diation dosage sustained by the GI tract, which is mainly derived from tumor location. In the concomitant boost technique, 50 GyE was delivered to cover the entire CTV by anterior and posterior beams and another posterior beam of 17.5 GyE was added as in Terashima’s method [16] (Supplementary Fig. 1). The essence of this method is that the boost beam be processed so as not to reach the GI tract. This method was slightly modified so that the irradi-ation dose of the GI tract in the boost beam was less than 10% of the isocenter dose. We set the dose constraints for the GI tract at 50 GyE and in only 1 patient was the duodenal dose beyond 50 GyE due to the tumor’s location. However, we accepted this plan since the volume and dose was small (D0.1cc: 51.8 GyE). The relative biological effectiveness value was determined to be 1.1 [17]. During treatment, all patients were treated with 155– 230 MeV proton beams, using a passive spreading method, and beams were delivered at the expiratory phase for a maximum of 0.3 seconds under free-breathing conditions [18]. Spinal bones and 2 sets of orthogonal digital radiographs were used for daily confirmation of the position. We routinely use proton-pump inhi-bitors to preserve the GI tract during the treatment course and treatment was performed after at least 3 hours of fasting (6 hours if the pancreas was especially close to the GI tract).