Image Assisted Optimization of Proton Radiation Therapy in Chordomas and Chondrosarcomas

NCT04832620 | Recruiting

• 1 other identifier: 41335
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Rationale: Chordomas and chondrosarcomas located in the axial skeleton are malignant neoplasms of bone. These tumors share the same clinical challenges, as the effect of the disease is more a function of their local aggressiveness than their tendency to metastasize (20% metastasize). The local aggressive behavior can cause debilitating morbidity and mortality by destruction of nearby located critical neurovascular structures. Imaging has, in addition to histopathology, a role in diagnosis and in guiding (neo)adjuvant and definitive treatment. Despite the low sensitivity to radiotherapy, proton radiotherapy has been successfully used as an adjunct to resection or as definitive treatment for aggressive chordomas and chondrosarcomas, making it a standard indication for proton therapy in the Netherlands. Chordomas and chondrosarcomas consist, especially after previous therapy, of non-viable and viable tumor components. Identification of these viable components by functional imaging is important to determine the effect of previous therapy, as change in total tumor volume occurs more than 200 days after change of functional imaging parameters. Objective: The main objective of this study is to determine if functional MRI parameters change within 6 months, and earlier than volumetric changes after start of proton beam therapy. This would allow timely differentiation between affected and unaffected (viable) tumor components, which can be used for therapy adjustment. Secondary objectives: Determine which set of parameters (PET-CT and secondary MRI) can predict clinical outcome (tumor specific mortality, development of metastases, morbidity secondary to tumor activity and morbidity secondary to treatment); determine what type of imaging can accurately identify viable tumor nodules relative to critical anatomical structures; improving understanding of relevance of changing imaging parameters by correlating these with resected tumor. Study design: Prospective cohort study Study population: LUMC patients diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton. A number of 20 new patients per year is expected. Main study parameters: Volumetric and functional MR imaging parameters including permeability parameters. Secondary parameters are generated by PET-CT (SUV, MTV and TLG), MR (perfusion, permeability and diffusion), therapy (proton beam dose mapping, surgery) and clinical outcome. End points are disease specific survival, progression free survival (including development of metastases), side effects of treatment, and functional outcome (see CRF). In patients who are treated with surgical resection following neo-adjuvant therapy, the surgical specimen will be correlated with imaging findings. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment and clinical management will not be affected in this study, thus the additional burden, risks, and benefits associated with participation in this study are minimal. Two extra MRI and one PET-CT examination will be planned during proton therapy.

Conditions

Bone Neoplasm of Vertebral Column; Chordoma; Chondrosarcoma; Magnetic Resonance Imaging; PET-CT; Proton Therapy

Keywords

Chordoma; Chondrosarcoma; MRI; PET-CT; Proton therapy

Outcome Measures

Primary Outcomes (1)

• Vp(max), Vp(min)

  MRI permeability parameter - tumor plasma volume

  At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment

Secondary Outcomes (16)

• Rel Enhancement (%)

  At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment

• Max Enhancement (%)

  At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment

• Max Rel Enhancement (%)

  At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment

• Time of arrival T0 (s)

  At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment

• Time To Peak (s)

  At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients referred to HollandPTC, or LUMC, or the Netherlands Committee of Bone tumors, histologically diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton (clivus, spine and sacrum), and accepted for standard proton beam therapy.

You may qualify if:

• Histologically diagnosed with primary or recurrent chordoma or chondrosarcoma in the axial skeleton (clivus, spine and sacrum)
• Accepted for standard proton beam therapy

You may not qualify if:

• Diagnosis other than chordoma or chondrosarcoma is made.
• Patient refuses (parts) of the standard treatment protocol.
• Patient refuses MRI due to claustrophobia.
• Patient not suitable for MRI due to the presence of MRI incompatible implants.
• Incapacitated patients.
• Patient doesn't allow coded data to be used for analysis.
• Patient is under 50 years of age.
• Lesion size less than 1cm.
• Patients with WHO 3 and higher.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• HollandPTC: collaborator
• Varian Medical Systems: collaborator

Study Sites (2)

HollandPTC

Delft, South Holland, 2629 JH, Netherlands

RECRUITING

LUMC

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

MeSH Terms

Conditions

Chordoma; Chondrosarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Study Officials

• Stijn Krol, MD PhD

  LUMC/HollandPTC

  PRINCIPAL INVESTIGATOR

• Hans Bloem, prof. MD PhD

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stijn Krol, dr. PhD

CONTACT

+31624539398; A.D.G.Krol@lumc.nl

Vesna Miladinovic

CONTACT

+31682225869; v.miladinovic@lumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiation oncologist

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 6, 2021
• Study Start: February 2, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

NL (2)