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Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma
Author(s) -
Christelle Bouchart,
Jean-Luc Engelholm,
Jean Closset,
Julie Navez,
Patrizia Loi,
Yeter Gökburun,
Thierry De Grez,
Laura Mans,
Alain Hendlisz,
Maria Antonietta Bali,
Pierre Eisendrath,
D. Van Gestel,
Matthieu Hein,
Luigi Moretti,
Jean–Luc Van Laethem
Publication year - 2021
Publication title -
therapeutic advances in medical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 49
eISSN - 1758-8359
pISSN - 1758-8340
DOI - 10.1177/17588359211045860
Subject(s) - medicine , clinical endpoint , irinotecan , adenocarcinoma , stereotactic biopsy , oxaliplatin , radiation therapy , folfirinox , oncology , chemotherapy , biopsy , radiology , cancer , colorectal cancer , clinical trial
Background: Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma.Materials and methods: Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC).Results: A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 versus 18.2 months, p = 0.02; PFS: 24.1 versus 7.1 months, p < 0.001). There was no survival difference between the BR and LAPC patients. The 1-year LC from SBRT was 74.1% and the median locoregional PFS was not reached for both BR and LAPC patients.Conclusions: iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials.

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