Carbon ion radiotherapy as definitive treatment in non-metastasized pancreatic cancer: study protocol of the prospective phase II PACK-study

Juergen Debus,Klaus Herfarth,Meinhard Kieser,Moritz Pohl,Patrick Naumann,Adriane Hommertgen,Jakob Liermann

doi:10.1186/s12885-020-07434-8

Abstract

BackgroundRadiotherapy is known to improve local tumor control in locally advanced pancreatic cancer (LAPC), although there is a lack of convincing data on a potential overall survival benefit of chemoradiotherapy over chemotherapy alone. To improve efficacy of radiotherapy, new approaches need to be evolved. Carbon ion radiotherapy is supposed to be more effective than photon radiotherapy due to a higher relative biological effectiveness (RBE) and due to a steep dose-gradient making dose delivery highly conformal.MethodsThe present Phase II PACK-study investigates carbon ion radiotherapy as definitive treatment in LAPC as well as in locally recurrent pancreatic cancer. A total irradiation dose of 48 Gy (RBE) will be delivered in twelve fractions. Concurrent chemotherapy is accepted, if indicated. The primary endpoint is the overall survival rate after 12 months. Secondary endpoints are progression free survival, safety, quality of life and impact on tumor markers CA 19–9 and CEA. A total of twenty-five patients are planned for recruitment over 2 years.DiscussionRecently, Japanese researches could show promising results in a Phase I/II-study evaluating chemoradiotherapy of carbon ion radiotherapy and gemcitabine in LAPC. The present prospective PACK-study investigates the efficacy of carbon ion radiotherapy in pancreatic cancer at Heidelberg Ion Beam Therapy Center (HIT) in Germany.Trial registrationThe trial is registered at ClinicalTrials.gov: NCT04194268 (Retrospectively registered on December, 11th 2019).

Highlights

Radiotherapy is known to improve local tumor control in locally advanced pancreatic cancer (LAPC), there is a lack of convincing data on a potential overall survival benefit of chemoradiotherapy over chemotherapy alone
There was no difference in overall survival, chemoradiotherapy was shown to improve local tumor control compared to chemotherapy alone
IcaobuzioDonahue et al could show that local tumor progression is related with approximately one third of all pancreatic cancer deaths [6], highlighting the necessity of effective treatment schemes for patients suffering from LAPC and from nonmetastasized locally recurrent pancreatic cancer

Summary

Introduction

Radiotherapy is known to improve local tumor control in locally advanced pancreatic cancer (LAPC), there is a lack of convincing data on a potential overall survival benefit of chemoradiotherapy over chemotherapy alone. An approach to overcome this gap of efficacy of photon irradiation is the use of particle therapy, which induces more direct radiation damage to the deoxyribonucleic acid (DNA) due to the known higher linear energy transfer (LET) corresponding with a higher relative biological effectiveness (RBE). Carbon ion radiotherapy shows higher RBE-values in pancreatic cancer than those commonly known from protons [10,11,12] It could be an effective treatment scheme for patients suffering from LAPC or non-metastasized locally recurrent pancreatic cancer

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