Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy.

Abstract

372 Background: In locally advanced pancreatic cancer, radiotherapy (RT) is an effective treatment modality, but challenged by conflicting results. Now, in the era of intensity-modulated radiation therapy (IMRT), dose escalation is possible without increasing the dose to organs-at-risk. We investigated whether RT dose escalation would improve treatment outcomes without increasing severe toxicity. Methods: From 2005 to 2015, a total of 497 locally advanced - including both borderline resectable and unresectable - pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy were included. A total of 281 (56.5%) patients received 3D conformal RT and 216 (43.5%) patients received IMRT. Most common dose scheme for IMRT was 58.42 Gy in 23 fractions (EQD2 61.05 Gy). Patients were divided into two groups; < 61 Gy group (n = 345) and ≥ 61 Gy group (n = 152). Overall survival (OS), progression-free survival (PFS), local failure-free rate (LFFR), distant failure-free rate (DFFR) and toxicity rates were assessed. Results: At a median follow-up time of 14.1 months (range, 2.3-128.5 months), OS, PFS, LFFR, and DFFR rates were significantly higher in ≥ 61 Gy group. The 1-year OS rates were 74.7% and 60.6% (p = 0.001) and 1-year PFS rates were 46.2% and 30.9% (p < 0.001), for ≥ 61 Gy and < 61 Gy group, respectively. The 1-year LFFR was 86.9% and 70.9% (p = 0.001) and 1-year DFFR was 56.4% and 45.8% (p = 0.007), respectively. After multivariate analysis, ≥ 61 Gy group remained a favorable significant factor for OS (p = 0.019), PFS (p = 0.001), LFFR (p = 0.004), and DFFR (p = 0.008). When 152 patients in each group were matched by propensity score matching, ≥ 61 Gy group still showed higher OS (p = 0.011), PFS (p = 0.016), and LFFR (p = 0.002), but not DFFR (p = 0.205). There was no acute gastrointestinal toxicity higher than Grade 3 in both groups. Late toxicity rates were also similar, with RT-related duodenal and gastric hemorrhage ( ≥ Grade 3) in 19 patients (5.5%) in < 61 Gy group and 7 patients (4.6%) in ≥ 61 Gy group. Conclusions: Patients who received higher RT dose showed not only improved PFS and LFFR but improved OS without an increase in severe toxicity. Dose escalation via IMRT is recommended for RT in locally advanced pancreatic cancer patients.

Effect of neoadjuvant radiotherapy on survival of non-metastatic pancreatic ductal adenocarcinoma: a SEER database analysis

“…However, the role of neoadjuvant radiotherapy in PDAC is still under debate due to the lack of relatively reliable data. Currently, neoadjuvant radiotherapy is mainly used for borderline resectable PDAC and locally advanced PDAC since which may improve the marginal negative resection rate and local control rate [12,13]. However, it is unclear whether neoadjuvant radiotherapy improves survival of patients with PDAC.…”

Biologically effective doses of 60-70Gy vs. >70Gy of stereotactic body radiotherapy (SBRT) combined with chemotherapy in locally advanced pancreatic cancer: protocol of a phase III study

“…As stated above, our previous studies have clari ed that BED 10 ≥60Gy may be associated with better prognosis, which was also proven by another study that demonstrated the correlation between BED 10 >70Gy and better outcomes [9]. In terms of hypofractionated IMRT, a Korean study evaluating almost 500 patients with LAPC also found that patients receiving ≥ 61Gy had improved LC, PFS and OS [14].…”

Effect of neoadjuvant radiotherapy on survival of non-metastatic Pancreatic Ductal Adenocarcinoma: A SEER Database Analysis

“…However, the role of neoadjuvant radiotherapy in PDAC is still under debate due to the lack of relatively reliable data. Currently, neoadjuvant radiotherapy is mainly used for borderline resectable PDAC and locally advanced PDAC since which may improve the marginal negative resection rate and local control rate 12,13 . However, it is unclear whether neoadjuvant radiotherapy improve survival of patients with PDAC.…”