Dose Escalation by Boosting Radiation Dose Within the Primary Tumor Using FDG-PET-CT Scan in Stage IB, II and III NSCLC

NCT01024829 | Unknown DMC

• 1 other identifier: PET Boost
• Study Type: interventional
• Target: 150
• Locations: 5 countries
• Sites: 7

Brief Summary

Increasing ("boosting") the radiation dose for patients with non-small cell lung carcinoma to the individual maximal dose which can safely be given. The question is if patients should receive this boost on the whole tumor on part of the tumor. Therefore patients are randomized for one of these two treatment options. All patients will receive 24 radiations. Dose increasement will be enabled by a so called integrated boost. Furthermore: \- PET imaging of hypoxia using \[18F\]HX4, single injection and then PET CT scanning two and four hours post injection.

Conditions

NSCLC

Keywords

Non small cell lung cancer; Inoperable; HX4

Outcome Measures

Primary Outcomes (1)

• Local progression-free survival at 1 year

  1 year

Secondary Outcomes (3)

• Toxicity

  1 year

• Overall survival

  1 year

• Quality of life

  1 year

Study Arms (2)

Whole tumor boost

OTHER

Patients in this arm will receive radiotherapy (66Gy) in 24 fractions of 2.75 Gy with an integrated boost to the primary tumor as a whole

Radiation: Radiotherapy

Boost 50% SUV area

OTHER

Patients in this arm receive radiotherapy (66Gy) in 24 fractions of 2.75Gy with an integrated boost to the 50% SUVmax area of the primary tumor (of the pre-treatment FDG-PET-CT scan)

Radiation: Radiotherapy

Interventions

Radiotherapy RADIATION

Radiotherapy

Boost 50% SUV area; Whole tumor boost

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \> 18 years with any subtype of pathologically proven (biopsy or cytology), non-small cell lung cancer. The diagnosis may be established from biopsy or cytology obtained from the primary tumor and/ or from metastatic lymph nodes.
• Minimal diameter of the primary tumor 4 cm, this to allow for boosting of sub-volumes.
• UICC TNM Stage T2-4, N0-3, M0 disease (TNM definition see appendix 2).
• Only stage IB-II patients who are nog candidates for surgery are study candidates.
• Measurable disease at registration.
• ECOG-performance status ≤ 2 (see appendix 6)
• Lung function: FEV1 and DLCO at least 40 % of the age-adjusted normal value
• Willing and able to give a written informed consent.
• Patients with locoregional recurrent lung tumor following surgery or a second primary cancer (at least 3 years after treatment) are eligible, unless a pneumonectomy was performed.
• SUVmax in the pre-treatment FDG-PET scan ≥ 5 for the primary tumor.
• Adequate organ function, including the following:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL.
• Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (AP), aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) ≤ 3.0 x ULN (AP, AST, and ALT ≤ 5 x ULN is acceptable if liver has tumor involvement).
• Renal: calculated creatinine clearance (CrCl) ≥ 45 ml/min based on the original weight based Cockcroft and Gault formula
• For women: Must be surgically sterile, postmenopausal, or compliant with a highly reliable contraceptive method (failure rate \<1%) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding.

You may not qualify if:

• Prior radiotherapy to the thorax.
• Clinical superior vena cava syndrome, malignant pleural effusion or malignant pericardial effusion.
• T4, specified as:Tumor growth in large blood vessels on spiral CT scan or encasement \>50%
• multiple nodules in the same or ipsilateral lobe(s).
• Post-obstructive atelectasis or infiltration that cannot be distinguished from tumor on a CT-PET scan.
• Patients with a diagnosis of other cancer within the last 3-years (except in situ carcinoma's and / or non-melanoma skin cancer).
• Pregnant women, lactating women

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• European Union: collaborator

Study Sites (7)

University Hospital Leuven, campus Gasthuisberg

Leuven, B-3000, Belgium

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

MAASTRO clinic

Maastricht, Limburg, 6229 ET, Netherlands

Location

NKI/AVL

Amsterdam, 1066CX, Netherlands

Location

Academic Medical Centre

Amsterdam, 1105AZ, Netherlands

Location

Karolinska Hospital

Stockholm, Sweden

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (5)

• Cooke SA, Belderbos JSA, Stam B, Reymen B, Lambrecht M, Fredberg Persson G, Faivre-Finn C, Dieleman EMT, van Diessen J, de Ruysscher D, Sonke JJ. Esophageal Toxicity After Dose-Escalated Radiation Therapy for Stage II-III Non-Small Cell Lung Cancer: A Secondary Analysis of the Phase 2 Randomized ARTFORCE PET-Boost Trial. Int J Radiat Oncol Biol Phys. 2025 Aug 1;122(5):1227-1237. doi: 10.1016/j.ijrobp.2025.03.001. Epub 2025 Mar 28.

  PMID: 40156600 DERIVED

• Cooke SA, de Ruysscher D, Reymen B, Lambrecht M, Fredberg Persson G, Faivre-Finn C, Dieleman EMT, Lewensohn R, van Diessen JNA, Sikorska K, Lalezari F, Vogel W, van Elmpt W, Damen EMF, Sonke JJ, Belderbos JSA. 18F-FDG-PET guided vs whole tumour radiotherapy dose escalation in patients with locally advanced non-small cell lung cancer (PET-Boost): Results from a randomised clinical trial. Radiother Oncol. 2023 Apr;181:109492. doi: 10.1016/j.radonc.2023.109492. Epub 2023 Jan 24.

  PMID: 36706958 DERIVED

• van Diessen J, De Ruysscher D, Sonke JJ, Damen E, Sikorska K, Reymen B, van Elmpt W, Westman G, Fredberg Persson G, Dieleman E, Bjorkestrand H, Faivre-Finn C, Belderbos J. The acute and late toxicity results of a randomized phase II dose-escalation trial in non-small cell lung cancer (PET-boost trial). Radiother Oncol. 2019 Feb;131:166-173. doi: 10.1016/j.radonc.2018.09.019. Epub 2018 Oct 13.

  PMID: 30327236 DERIVED

• Defraene G, La Fontaine M, van Kranen S, Reymen B, Belderbos J, Sonke JJ, De Ruysscher D. Radiation-Induced Lung Density Changes on CT Scan for NSCLC: No Impact of Dose-Escalation Level or Volume. Int J Radiat Oncol Biol Phys. 2018 Nov 1;102(3):642-650. doi: 10.1016/j.ijrobp.2018.06.038. Epub 2018 Jul 2.

  PMID: 30244882 DERIVED

• van Elmpt W, Zegers CML, Reymen B, Even AJG, Dingemans AC, Oellers M, Wildberger JE, Mottaghy FM, Das M, Troost EGC, Lambin P. Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion. Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):240-248. doi: 10.1007/s00259-015-3169-4. Epub 2015 Sep 4.

  PMID: 26338178 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• José Belderbos, MD, PhD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 3, 2009
• Study Start: May 1, 2010
• Primary Completion: December 1, 2020
• Study Completion: March 1, 2022
• Last Updated: January 21, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); NL (3); GB (1); BE (1); SE (1)