Top

Published in:

01-12-2020 | Particle Therapy | Study protocol

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

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

Published in: BMC Cancer | Issue 1/2020

Abstract

Background

Radiotherapy 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.

Methods

The 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.

Discussion

Recently, 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 registration

The trial is registered at ClinicalTrials.gov: NCT04194268 (Retrospectively registered on December, 11th 2019).

Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic Cancer: global trends, etiology and risk factors. World J Oncol. 2019;10(1):10–27.PubMedPubMedCentralCrossRef

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed

Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–77.CrossRefPubMed

Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–20.PubMedPubMedCentralCrossRef

Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, et al. Effect of Chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic Cancer controlled after 4 months of gemcitabine with or without Erlotinib: the LAP07 randomized clinical trial. JAMA. 2016;315(17):1844–53.PubMedCrossRef

Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27(11):1806–13.PubMedPubMedCentralCrossRef

Kavanagh BD, Pan CC, Dawson LA, Das SK, Li XA, Ten Haken RK, et al. Radiation dose-volume effects in the stomach and small bowel. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S101–7.PubMedCrossRef

Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S10–9.PubMedPubMedCentralCrossRef

Erkan M, Kurtoglu M, Kleeff J. The role of hypoxia in pancreatic cancer: a potential therapeutic target? Expert Rev Gastroenterol Hepatol. 2016;10(3):301–16.PubMedCrossRef

10.

El Shafie RA, Habermehl D, Rieken S, Mairani A, Orschiedt L, Brons S, et al. In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines. J Radiat Res. 2013;54(Suppl 1):i113–9.PubMedPubMedCentralCrossRef

11.

Matsui Y, Asano T, Kenmochi T, Iwakawa M, Imai T, Ochiai T. Effects of carbon-ion beams on human pancreatic cancer cell lines that differ in genetic status. Am J Clin Oncol. 2004;27(1):24–8.PubMedCrossRef

12.

Prescribing, recording, and reporting proton-beam therapy: contents. Journal of the International Commission on Radiation Units and Measurements. 2007;7(2). https://doi.org/10.1093/jicru/ndm021.

13.

Shinoto M, Yamada S, Terashima K, Yasuda S, Shioyama Y, Honda H, et al. Carbon ion radiation therapy with concurrent gemcitabine for patients with locally advanced pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2016;95(1):498–504.PubMedCrossRef

14.

Combs SE, Habermehl D, Kessel K, Bergmann F, Werner J, Brecht I, et al. Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer. Outcome analysis and comparison with a 3D-treated patient cohort. Strahlenther Onkol. 2013;189(9):738–44.PubMedCrossRef

15.

Kawashiro S, Yamada S, Isozaki Y, Nemoto K, Tsuji H, Kamada T. Carbon-ion radiotherapy for locoregional recurrence after primary surgery for pancreatic cancer. Radiother Oncol. 2018;129(1):101–4.PubMedCrossRef

16.

Habermehl D, Brecht IC, Bergmann F, Welzel T, Rieken S, Werner J, et al. Chemoradiation in patients with isolated recurrent pancreatic cancer - therapeutical efficacy and probability of re-resection. Radiat Oncol. 2013;8:27.PubMedPubMedCentralCrossRef

17.

Steinstrater O, Grun R, Scholz U, Friedrich T, Durante M, Scholz M. Mapping of RBE-weighted doses between HIMAC- and LEM-based treatment planning systems for carbon ion therapy. Int J Radiat Oncol Biol Phys. 2012;84(3):854–60.PubMedCrossRef

18.

Weyrather WK, Kraft G. RBE of carbon ions: experimental data and the strategy of RBE calculation for treatment planning. Radiother Oncol. 2004;73(Suppl 2):S161–9.PubMedCrossRef

19.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.PubMedCrossRef

20.

Shinoto M, Yamada S, Yasuda S, Imada H, Shioyama Y, Honda H, et al. Phase 1 trial of preoperative, short-course carbon-ion radiotherapy for patients with resectable pancreatic cancer. Cancer. 2013;119(1):45–51.PubMedCrossRef

21.

Liermann J, Shinoto M, Syed M, Debus J, Herfarth K, Naumann P. Carbon ion radiotherapy in pancreatic cancer: a review of clinical data. Radiother Oncol. 2020;147:145–50.PubMedCrossRef

22.

Vitolo V, Cobianchi L, Brugnatelli S, Barcellini A, Peloso A, Facoetti A, et al. Preoperative chemotherapy and carbon ions therapy for treatment of resectable and borderline resectable pancreatic adenocarcinoma: a prospective, phase II, multicentre, single-arm study. BMC Cancer. 2019;19(1):922.PubMedPubMedCentralCrossRef

23.

Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker-Prietz A, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121(7):1128–37.PubMedCrossRef

24.

Shinoto M, Shioyama Y, Matsunobu A, Okamoto K, Suefuji H, Toyama S, et al. Dosimetric analysis of upper gastrointestinal ulcer after carbon-ion radiotherapy for pancreatic cancer. Radiother Oncol. 2016;120(1):140–4.PubMedCrossRef

Title: Carbon ion radiotherapy as definitive treatment in non-metastasized pancreatic cancer: study protocol of the prospective phase II PACK-study
Authors: Jakob Liermann
Patrick Naumann
Adriane Hommertgen
Moritz Pohl
Meinhard Kieser
Juergen Debus
Klaus Herfarth
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Particle Therapy
Radiotherapy
Pancreatic Cancer
Pancreatic Cancer
Published in: BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-020-07434-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2020

Effects of reduced platelet count on the prognosis for patients with non-small cell lung cancer treated with EGFR-TKI: a retrospective study

Evaluation of radioactive 125I seed implantation for the treatment of refractory malignant tumours based on a CT-guided 3D template-assisted technique: efficacy and safety

Real-world patient-reported outcomes of women receiving initial endocrine-based therapy for HR+/HER2− advanced breast cancer in five European countries

A pilot study of improved psychological distress with art therapy in patients with cancer undergoing chemotherapy

Three-year outcome after transanal versus laparoscopic total mesorectal excision in locally advanced rectal cancer: a multicenter comparative analysis

Clinical significance of peripheral blood and tumor tissue lymphocyte subsets in cervical cancer patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer