Hypofractionated sequential radiotherapy boost: a promising strategy in inoperable locally advanced pancreatic cancer patients

Gian Carlo Mattiucci, Luca Boldrini, Alessia Nardangeli, Andrea D’Aviero, Milly Buwenge, Francesco Cellini, Francesco Deodato, Nicola Dinapoli, Vincenzo Frascino, Gabriella Macchia, Alessio Giuseppe Morganti, Vincenzo Valentini

Research output: Contribution to journalArticlepeer-review


Purpose: To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints. Materials and methods: Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30 Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up. Results: Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20 Gy in 5 fr (N: 6; 19.4%), 20 Gy in 4 fr (N: 5; 16.2%), 25 Gy in 5 fr (N: 18; 58.0%) and 30 Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19 months (range 1–156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28 months; range 2–139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18 months (range 1–139). The 2-year OS after HRB was 57.4%, while 2-year OS from diagnosis was 77.3%. Conclusion: Treatment intensification with hypofractionated radiotherapy boost is well tolerated in pts affected by unresectable LAPC previously treated with CT/CRT. Its rates of local and pain control are encouraging, supporting its introduction in clinical practice. Timing, schedule and dose of HRB need to be further investigated to personalize therapy and optimize clinical advantages.

Original languageEnglish
Pages (from-to)661-667
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Issue number3
Publication statusPublished - Mar 2021


  • Hypofractionation
  • Locally advanced pancreatic adenocarcinoma
  • Radiotherapy boost

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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