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Open Access Study protocol

Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial

Stephanie E Combs1*, Meinhard Kieser2, Daniel Habermehl1, Jürgen Weitz3, Dirk Jäger4, Piero Fossati5, Roberto Orrechia5, Rita Engenhart-Cabillic6, Richard Pötter7, Manjit Dosanjh8, Oliver Jäkel19, Markus W Büchler3 and Jürgen Debus1

Author affiliations

1 Deparment of Radiation Oncology, Im Neuenheimer Feld 400, University Hospital of Heidelberg, Heidelberg 69120, Germany

2 Department of Biostatistics, Im Neuenheimer Feld 305, University Hospital of Heidelberg, Heidelberg 69120, Germany

3 Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, Heidelberg 69120, Germany

4 Nationales Centrum für Tumorerkrankungen (NCT), Medizinische Onkologie, Im Neuenheimer Feld 360, Heidelberg 69120, Germany

5 Fondazione CNAO - Centro Nazionale di Adroterapia Oncologica, Via Caminadella, 16, Milano 20123, Italy

6 Department of Radiation Oncology, Baldingerstraße, University Hospital of Marburg, Marburg 35043, Germany

7 Department of Radiation Oncology, University of Vienna, Währinger Gürtel 18-20, Wien 1090, Austria

8 CERN, Geneva 23 1211, Switzerland

9 Heidelberger Ionenstrahl Therapiezentrum (HIT), Im Neuenheimer Feld 450, Heidelberg 69120, Germany

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Citation and License

BMC Cancer 2012, 12:137  doi:10.1186/1471-2407-12-137

Published: 3 April 2012

Abstract

Background

Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed.

Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.

Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions.

Methods and design

In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study.

Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied.

The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival.

Discussion

With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial.

Trial registration

NCT01528683