Patients diagnosed with primary unresectable LAPC or LRPC after radical resection in our hospital from June, 2004 to February, 2018 were retrospectively reviewed. All of them received definitive CRT with or without neoadjuvant chemotherapy. Unresectable cancer was defined as superior mesenteric artery or celiac axis encasement> 180 degrees, unreconstructible superior mesenteric vein (SMV) / portal occlusion, or aortic invasion. Exclusion criteria included: (1) distant metastasis before radiotherapy, (2) patients received tumor resection after CRT, (3) LRPC patients with adjuvant RT after tumor resection before local recurrence, (4) missing data of clinical treatment. Detail of patients enrollment is shown in Fig. 1.
Totally, 65 patients are included into our study, with 47 unresectable LAPC patients and 18 unresectable LRPC patients. Among the 47 patients, primary tumor lay in pancreatic head, neck or uncinate process, and body or tail in 22, 7 and 18 patients, respectively. Among the 18 unresectable LRPC patients, tumor recurred in situ, at regional lymph nodes, and at both sites in 8, 6 and 4 patients, respectively.
The median age for all patients were 58 years (range 33-82 years). Male and female patients accounted for 60% and 40%, respectively. Other clinical characteristics are shown in Table 1.
All the radiologic image data were re-evaluated by a senior radiologist to assess the possibility of radical resection according to the guidelines from National Comprehensive Cancer Network and tumor response according to the RECIST criteria V1.1.
To fully appreciate the location of the gross tumor volume (GTV), the tumor is evaluated on all triphasic diagnostic scans (CT/MR) as well as on CT simulation images, to create an GTV. In recent years, an internal GTV (GTVin) is also defined by omitting the tumor part invading or locating approximate to the gastrointestinal tract, as shown in Fig. 2, for dose escalation, to treat GTVin volume to a higher dose level respecting the gastrointestinal tract tolerance. The clinical target volume (CTV) comprises a 5-10mm expansion from the GTVin all directions and may need to be further expanded to include areas at risk of microscopic extension, as well as nodal elective irradiation around the celiac axis, superior mesenteric artery (SMA), and SMV (generally starting at the origin of the arteries and including the vessels at the same axial slice levels as the GTV). The CTV can extend into bowel structures, ensuring coverage of microscopic risk of disease in the adjacent duodenum and nodal basins. Planning treatment volume (PTV) was generated by adding a 5-mm margin in all directions to the CTV in consideration of respiratory management.
There were 5 radiation techniques, including CT-SIM, 3D-CRT, IMRT, VMAT and SBRT. 17 patients accepted CT-SIM/3D-CRT radiation, 42 patients were treated with IMRT/VMAT and SBRT was applied to 6 patients. Radiotherapy delivered doses from 33 to 61.6 Gy, in 5-30 fractions. The majority of dose fraction was mainly conventional fraction (1.8-2.9 Gy) and a small part of patients received high-dose fraction (3.8-9 Gy) radiation. In addition, 23 person (35.4%) accepted contaminant boost radiation for GTVin. The average dose boost is totally 6 Gy (4-8 Gy). Biological effective dose (BED) equals to nd×[1+d/(α/β)]. (n refers to fraction times, d refers to fraction dose, and nd refers to total dose. The α/β was assigned as 10.) BED10 of the whole cohort ranged from 46.7 to 85.5 Gy. (Fig. 4)
46 patients accepted neoadjuvant chemotherapy before irradiation: 7 (10.8%) with single-agent gemcitabine or tegafur (S1), 30 (46.2%) with GS-based agents, 9 (13.8%) with FOLFIRINOX. 37 patients received concurrent chemotherapy, mainly using S1. 34 patients received adjuvant chemotherapy, including Gemcitabine, S-1, mFOLFOX or FOLFIRINOX.
The follow-up was performed regularly after treatments. Physical examination, serum CA199 detection and imaging examination (abdomen CT or magnetic resonance imaging) were implemented at follow-up. Afterwards the patients were followed by an outpatient interview or household registration system. The last follow-up was completed on 1 April, 2020.
Overall survival (OS) was defined as the time from the start of CRT to death or the last follow-up. All statistical analyses were conducted using the R statistical package (R software version 4-0.0; R foundation for statistical computing. Vienna, Austria). The Kaplan-Meier method was used to analyze OS. Differences between two groups were tested using Log-rank. Variables with P< 0.22 in the univariate analysis were subjected to the multivariate model. Cox proportion hazards model was performed to analyze variables. A two-sided P-value < 0.05 was considered statistically significant.