Date Published: April 12, 2019
Publisher: Public Library of Science
Author(s): Jinhong Jung, Sang Min Yoon, Jin-hong Park, Dong-Wan Seo, Sang Soo Lee, Myung-Hwan Kim, Sung Koo Lee, Do Hyun Park, Tae Jun Song, Baek-Yeol Ryoo, Heung-Moon Chang, Kyu-pyo Kim, Changhoon Yoo, Jae Ho Jeong, Song Cheol Kim, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Yoon Young Jo, Jongmoo Park, Jong Hoon Kim, Sunil Krishnan.
Stereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC.
We retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24–36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed.
A total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients.
LAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.
Recent advances in radiotherapy techniques, including four-dimensional image acquisition, image-guided treatment, and respiratory-gated delivery as well as better understanding of normal organ tolerance to radiation have enabled delivery of high-dose radiation to tumors while minimizing the radiation dose to normal organs. Stereotactic body radiation therapy (SBRT) is a form of short course radiotherapy that allows conformal and accurate delivery of high doses of radiation. SBRT has demonstrated high rate of local control in patients with lung cancer or other malignancies [1,2].
Several studies on conventional fractionated radiotherapy for LAPC showed that although the major patterns of treatment failure was DM, there were high rates of local progression that led to development of pancreatic pain, obstruction symptoms, and other morbidities that decrease the quality of life . Therefore, improving local control is still an important aim of radiotherapy in LAPC patients. SBRT with single fraction for LAPC could give excellent FFLP: early SBRT studies for LAPC used single fraction radiotherapy and reported 1-year FFLP rates of 84 to 100% [7,8,12,14]. However, single-fraction SBRT was shown to result in significant late complication (grade 2 or above late toxicity of 13–47%). Recently, Herman et al. reported reduced incidence of late GI toxicity (grade 3 or above late toxicity of 6%) with fractionated SBRT of 33 Gy in 5 fractions compared with a historical cohort of patients treated with gemcitabine plus a single 25-Gy fraction SBRT . Several studies of fractionated SBRT also showed favorable 1-year FFLP rates of 70–87% and minimal toxicities (Table 4) [10,11,13,15,16]. Considering equivalent dose in 2 Gy fractions (EQD2, using the linear-quadratic model, assuming an α/β of 10 Gy for pancreatic tumor), the prescribed dose of fractionated SBRT studies was similar to those of conventional CRT studies. However, fractionated SBRT showed comparable local control rate with single-fraction SBRT. In the present study, 1-year FFLP rate was 80.1%, which is in line with those of previous studies (Table 4). Furthermore, acute and late toxicities were low and similar to those of previous fractionated SBRT studies. All 95 patients received SBRT using a respiratory-gated VMAT or IMRT technique, and three patient experienced grade 3 acute GI toxicity (nausea and vomiting), while another 3 patients experienced grade 3 late toxicity (2 duodenal ulcer bleeding and 1 gastric ulcer perforation). All acute and late complications were mitigated with conservative management and no patient died of treatment-related toxicities. Considering the poor prognosis of LAPC patients, our dose-fraction scheme of 28 Gy in 4 fractions seems to be a reasonable option regarding local control and toxicity.