State of the Art Photon Therapy Versus Particle Therapy for Small Lung Tumors; a Planning Study Based on a Reference Dataset of Patients (Lung stage I)

In Silico Clinical Trial, Comparing State of the Art Photon Modalities With Proton and 12C-ion Therapy for Stage I NSCLC: A Multicentric ROCOCO Planning Study Based on a Reference Dataset of Patients

Compared to conventional radiotherapy with photons (CRT), particle therapy (PT) has the potential to inflict maximum damage on tumors with minimum collateral damage to neighboring healthy tissue. Given that the cost of particle therapy (PT) is considerably higher than that of conventional radiotherapy (RT) with photons, it is necessary to establish whether these higher costs are worthwhile in light of the expected advantages. Thus, clear evidence of the situations in which PT outperforms conventional photon treatment is needed.

In a previous ROCOCO study (lung stage I-IIIB) an inhomogeneous group of patients with regard to tumor stage and size was included1. Conformal radiotherapy and Intensity Modulated Radiotherapy were used in the comparison. In this study patients with smaller tumors are included (stage I). A stereotactic treatment schedule and more advanced treatment techniques, such as CyberKnife, RapidArc, IMRT and Tomotherapy, are eligible for these kind of lesions. As a result the comparison as demonstrated in our previous study maybe invalid. We propose to investigate to what extend proton and 12C-ion therapy decrease the amount of irradiated normal tissue compared to state of the art photon modalities in stage I lung cancer patients.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer

Detailed Description

For this in silico planning study all treatment plans will be performed in centers that are already operating and have experience in treatment planning. IMRT treatment plans will be calculated in Eindhoven (NL), Tomotherapy plans in Deventer (NL), Cyberknife plans in Liege (BE) and RapidArc treatment plans in Hasselt (BE). Proton treatment plans will be performed at the University of Pennsylvania (USA) and the C-ion treatment plans at the University of Marburg (GE).

A dataset with state-of-the-art image data is available. 25 patients will be included according to a-priori defined selection criteria. Each patient will function as his or her own control. For this reason, the number of patients per tumor group can be limited to 25 patients per tumor group (power = 80%, alpha = 5%).

The datasets will be stored on a secure website hosted by MAASTRO. High quality CT-images will be used for radiotherapy treatment planning. Secondary image information such as FDG-PET and MRI will be used for GTV delineation. GTV and all relevant OARs will be delineated in MAASTRO (NL). The GTV to PTV margin will be determined by the individual institutes according to the treatment technique and treatment modality.

Photons will be planned with state of the art treatment techniques. Protons will be planned using active beam delivery with Intensity Modulated proton therapy (IMPT)and carbon-ions with a pencil beam delivery treatment planning technique with gantry. Each participating center will use its own treatment planning system according to standard practice at that center. The same tumor dose, overall treatment time (OTT) and an equal number of fractions will be used for all treatment modalities.

Photon, proton and C-ion treatments will be compared based on dosimetric parameters on normal tissues. DVH's will be calculated for the OARs. In addition, the NTCP for a fixed tumor dose will be determined. Cobalt Gy equivalent doses will be used when reporting the proton and carbon-ion dose. In the case of protons, a constant RBE value of 1.1 will be used for both the tumor and the normal tissues. The RBE of carbon-ions will be calculated based on the models used by the participating centers.

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 ET
      • Maastro Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of 25 NSCLC patients; stages I (cT1/cT2aN0M0). Consecutive patients were identified from October 2009 onwards in MAASTRO clinic, Maastricht. All patients received respiratory gated CT (4DCT) scans. All were patients referred for primary radiotherapy or chemo radiation.

Description

Inclusion Criteria:

• >18 years of age
• referred for primary radiotherapy or chemo radiation
• NSCLC stage I
• received respiratory gated CT (4DCT) scans

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
NSCLC stage I; Consecutive patients were identified from October 2009 onwards in MAASTRO clinic, Maastricht. All patients received respiratory gated CT (4DCT) scans. All were patients referred for primary radiotherapy or chemo radiation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation exposure for organs at risk (OAR) in a stereotactic lung radiotherapy treatment.	A wide range of organs is included, to be able to document doses to organs that are further away from the target volume, and also to quantify low doses to organs. Included OAR's are; left lung, right lung, (part of the) ribs if less then 2 cm from the CTV, for non-apical tumors: liver, spinal canal resembling the spinal cord, esophagus (full length), trachea, and main bronchi up to the first bifurcation, skin (with a thickness of standardized 4 mm), thyroid area, heart, mediastinal great vessels (aorta, vena cava, main lung arteries, ...), portacath, pacemaker (or any other implanted device to be avoided), brachial plexus and stomach.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The risk of side effects in the irradiated normal tissue	1 year

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Collaborators: University of Pennsylvania
• Investigators: Study Director: Esther Troost, PhD, Maastro Clinic, The Netherlands; Study Director: Erik Roelofs, Maastro Clinic, The Netherlands; Study Director: Esther Bloemen, Maastro Clinic, The Netherlands

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 15, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (Estimate): January 16, 2014

Study Record Updates

• Last Update Posted (Estimate): January 12, 2016
• Last Update Submitted That Met QC Criteria: January 11, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: NSCLC; cT1/cT2aN0M0; Stereotactic lung treatment; MAASTRO; age >18 years
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ROCOCO Lung stage I