Longitudinal Registry Including Patients Treated With Heavy Particles

CNAO REgistry triAL - REGAL

The purpose of this registry is to collect retrospective and prospective standardized data of patients treated with particle therapy, either with protons or carbon ions, at the National Center for Oncological Hadrontherapy (CNAO) based in Pavia.

By keeping track of the patients treated, it will allow the investigators to periodically analyze and evaluate data collected of daily clinical activity. This will help gathering more information on the results of particle therapy and will provide the basis for in depth evaluation of patients' outcome with respect to the delivered treatment.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Radiation Toxicity; Oncology; Radiotherapy Side Effect; Radiation Exposure; Rare Disease
• Intervention / Treatment: Radiation: Heavy-ion therapy (hadrontherapy)

Detailed Description

Hadrontherapy is a unique radiotherapy (RT) that uses positively charged particles, namely protons and carbons, rather than photons used in conventional RT, to treat cancer.

Particle therapy represents a coming together of physics research applied to oncology and it is currently the most advanced form of radiotherapy for the treatment of tumors that are particularly radio resistant or located nearby sensitive structures.The strength of hadrontherapy lies in the unique physical and radiobiological properties of these particles. Indeed, protons and carbon ions have several biological advantages compared to conventional photon radiotherapy.

In this scenario we aim at constructing a patient registry to retrospectively and prospectively collect real-world data on all cancer patients treated at CNAO, either with protons or carbon ion radiation, independently of their disease (multiple cohorts will be included) for which they were treated.

We aim at collecting data on the natural history of the disease (how the disease presents, develops and progress, its association with other conditions). Those data will allow us to assess prognostic and predictive factors to evaluate treatment effects and toxicities and to provide evidence of the role of radiation oncology in a multidisciplinary approach.

Such registry will be used to generate clinical evidence and high-quality data that could better define the indications for heavy particles therapy and become a resource for the wider scientific community.

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: Chiara Campo, PhD; Phone Number: +39 0382078407; Email: campo@cnao.it
• Study Contact Backup: Name: Cristina Bono; Phone Number: +39 0382078613; Email: bono@cnao.it

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • National Center for Oncological Hadrontherapy (CNAO)
    • Principal Investigator: Ester Orlandi, MD
    • Contact: Cristina Bono; Phone Number: +39 0382078613; Email: bono@cnao.it
    • Contact: Chiara Campo, PhD; Phone Number: +39 0382-078 407; Email: campo@cnao.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients treated with particle therapy, protons and/or carbon ions, at the National Center for Oncological Hadrontherapy (CNAO), based in Pavia, who have signed the written informed consent document, can be enrolled in the study

Description

Inclusion Criteria:

• Patients treated with heavy particles at Fondazione CNAO, Pavia
• Patients who have the ability to understand and be willing to sign a written informed consent document

Exclusion Criteria:

• Patients or legal guardians who are unable to understand informed consent document

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Brain tumors, skull base tumors, spinal cord tumors; NEUROPARTICLE	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.
Ocular melanomas	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.
Head and Neck tumors	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.
Tumors of thorax and/or abdomen; GI-Particle	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.
Pelvic tumors; GYN-Particle	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.
Sarcomas and tumors of limbs; SarTAP-Particle	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.
Pediatric tumors	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.
Mobile spine and sacral tumors	Radiation: Heavy-ion therapy (hadrontherapy); Only data available from routine clinical practice at the National Center for Oncological Hadrontherapy (CNAO), based Pavia, will be collected. Intervention is not assigned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real world data collection	To collect real world data of patients treated with radiotherapy, to support particle radiotherapy and to provide evidence of the role of radiation oncology within the multidisciplinary approach.	50 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease evolution	To analyze the disease course and treatment performed by collecting demographic, disease characteristics and delivered treatment	50 years
Predicitive models	To collect details about the radiation treatment and radiobiological parameters to develop predictive models (outcome and toxicity)	50 years
Outcome data	To collect outcome data (in terms of overall survival, progression free-survival and local control) and to correlate them with the delivered treatment	50 years
Toxicities	To define acute, intermediate and late toxicities, according to CTCAE v 5.0 and to correlate it with the delivered treatment	50 years
QoL	To collect data on standardized QoL questionnaires and PROMS (e,g EORTC C30, EQDL) at 6, 12. 18, 24, 36 months and to correlate them with the delivered treatment	50 years
Future research	To generate hypotheses for further research	50 years

Collaborators and Investigators

• Sponsor: CNAO National Center of Oncological Hadrontherapy

Publications and helpful links

General Publications

• Tinganelli W, Durante M. Carbon Ion Radiobiology. Cancers (Basel). 2020 Oct 17;12(10):3022. doi: 10.3390/cancers12103022.
• Durante M, Paganetti H. Nuclear physics in particle therapy: a review. Rep Prog Phys. 2016 Sep;79(9):096702. doi: 10.1088/0034-4885/79/9/096702. Epub 2016 Aug 19.
• Kraft G. The radiobiological and physical basis for radiotherapy with protons and heavier ions. Strahlenther Onkol. 1990 Jan;166(1):10-3.
• Weber KJ, Flentje M. Lethality of heavy ion-induced DNA double-strand breaks in mammalian cells. Int J Radiat Biol. 1993 Aug;64(2):169-78. doi: 10.1080/09553009314551261.
• Mizoe JE, Hasegawa A, Jingu K, Takagi R, Bessyo H, Morikawa T, Tonoki M, Tsuji H, Kamada T, Tsujii H, Okamoto Y; Organizing Committee for the Working Group for Head Neck Cancer. Results of carbon ion radiotherapy for head and neck cancer. Radiother Oncol. 2012 Apr;103(1):32-7. doi: 10.1016/j.radonc.2011.12.013. Epub 2012 Feb 8.
• Weber DC, Langendijk JA, Grau C, Thariat J. Proton therapy and the European Particle Therapy Network: The past, present and future. Cancer Radiother. 2020 Oct;24(6-7):687-690. doi: 10.1016/j.canrad.2020.05.002. Epub 2020 Aug 1.
• Langendijk JA, Orecchia R, Haustermans K, Zips D, Balosso J, Lacombe D, Lievens Y, Weber DC, Grau C, Troost EGC. Prospective data registration and clinical trials for particle therapy in Europe. Radiother Oncol. 2018 Jul;128(1):9-13. doi: 10.1016/j.radonc.2018.06.001. Epub 2018 Jul 7.
• Grau C, Durante M, Georg D, Langendijk JA, Weber DC. Particle therapy in Europe. Mol Oncol. 2020 Jul;14(7):1492-1499. doi: 10.1002/1878-0261.12677. Epub 2020 Apr 22.

Helpful Links

• CNAO website

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2021
• Primary Completion (Estimated): June 4, 2030
• Study Completion (Estimated): June 4, 2071

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Cancer; Radiotherapy; Oncology; Protons; Hadrontherapy; Rare cancer; Carbon Ions; Heavy ions
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Rare Diseases
• Other Study ID Numbers: CNAO OSS 25 2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No