Risk Adapted Ablative Radiotherapy After Intensive Chemotherapy for Locally Advanced Pancreatic Cancer

Gabriella Rossi; Nicola Simoni; Salvatore Paiella; Roberto Rossi; Martina Venezia; Renato Micera; Giuseppe Malleo; Roberto Salvia; Tommaso Giuliani; Anthony Di Gioia; Alessandra Auriemma; Michele Milella; Stefania Guariglia; Carlo Cavedon; Claudio Bassi; Renzo Mazzarotto

doi:10.3389/fonc.2021.662205

Risk Adapted Ablative Radiotherapy After Intensive Chemotherapy for Locally Advanced Pancreatic Cancer

Front Oncol. 2021 Apr 20:11:662205. doi: 10.3389/fonc.2021.662205. eCollection 2021.

Authors

Gabriella Rossi¹, Nicola Simoni¹, Salvatore Paiella², Roberto Rossi¹, Martina Venezia¹, Renato Micera¹, Giuseppe Malleo², Roberto Salvia², Tommaso Giuliani², Anthony Di Gioia², Alessandra Auriemma³, Michele Milella³, Stefania Guariglia⁴, Carlo Cavedon⁴, Claudio Bassi², Renzo Mazzarotto¹

Affiliations

¹ Department of Radiation Oncology, University of Verona Hospital Trust, Verona, Italy.
² Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.
³ Department of Oncology, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.
⁴ Department of Medical Physics, University of Verona Hospital Trust, Verona, Italy.

Abstract

Background and objective: To assess the efficacy of a Risk-Adapted Ablative Radiotherapy (RAdAR) approach, after intensive induction chemotherapy, in patients with locally advanced pancreatic cancer (LAPC).

Material and methods: Patients with LAPC who received RAdAR following induction chemotherapy from January 2017 to December 2019 were included in this observational study. The RAdAR approach consisted of an anatomy- and simultaneous integrated boost (SIB)-based dose prescription strategy. RAdAR was delivered with stereotactic ablative radiation therapy (SAbR), administering 30 Gy in 5 fractions to the tumor volume (PTV_t) and 50 Gy SIB (BED₁₀ 100 Gy) to the vascular involvement, or with (hypo-)fractionated ablative radiotherapy (HART) prescribing 50.4 Gy in 28 fractions to the PTV_t, with a vascular SIB of 78.4 Gy (BED₁₀ 100 Gy). Primary end points were freedom from local progression (FFLP), overall survival (OS), and progression-free survival (PFS).

Results: Sixty-four LAPC patients were included. Induction chemotherapy consisted of gemcitabine/nab-paclitaxel in 60.9% and FOLFIRINOX in 39.1% of cases. SAbR was used in 52 (81.2%) patients, and HART in 12 (18.8%). After RAdAR, surgery was performed in 17 (26.6%) patients. Median follow-up was 16.1 months. Overall local control (LC) rate was 78.1%, with no difference between resected and non-resected patients (2-year FFLP 75.3% vs 56.4%; p = 0.112). Median OS and PFS were 29.7 months and 8.7 months, respectively, for the entire cohort. Resected patients had a better median OS (not reached versus 26.1 months; p = 0.0001) and PFS (19 versus 5.6 months; p < 0.0001) compared to non-resected patients. In non-resected patients, no significant difference was found between SAbR and HART for median FFLP (28.1 versus 18.5 months; p = 0.614), OS (27.4 versus 25.3 months; p = 0.624), and PFS (5.7 versus 4.3 months; p = 0.486). One patient (1.6%) experienced acute grade 4 gastro-intestinal bleeding. No other acute or late grade ≥ 3 toxicities were observed.

Conclusions: The RAdAR approach, following intensive induction chemotherapy, is an effective radiation treatment strategy for selected LAPC patients, representing a promising therapeutic option in a multimodality treatment regimen.

Keywords: SAbR; SBRT (stereotactic body radiation therapy); ablative dose; hypofractionated ablative radiation; locally advanced; pancreatic cancer.