Clinical trial NCT04832620: Image Assisted Optimization of Proton Radiation Therapy in Chordomas and Chondrosarcomas
Official title: Defining Optimal Imaging Strategies for Diagnosis, Treatment, and Treatment Evaluation of Chordomas and Chondrosarcomas of the Axial Skeleton
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Bone Neoplasm of Vertebral Column
Chordoma
Chondrosarcoma
Magnetic Resonance Imaging
PET-CT
Proton Therapy
Keywords: Chordoma
Chondrosarcoma
MRI
PET-CT
Proton therapy
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: HollandPTC
name: Varian Medical Systems
First posted: 2021-04-06
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Vp(max), Vp(min)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
Secondary outcomes:
measure: Rel Enhancement (%)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Max Enhancement (%)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Max Rel Enhancement (%)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Time of arrival T0 (s)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Time To Peak (s)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Wash In Rate (sˉ¹)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Wash Out Rate (sˉ¹)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Brevity of Enhancement (s)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Ktrans
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: kep
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Ve
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: Area under the curve (AUC)
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: mean ADC, Min ADC, Max ADC
timeFrame: At inclusion, 4 and 8 weeks, 5,11,17 and 23 months after the start date of proton therapy treatment
measure: SUV
timeFrame: At inclusion and and 11 months following the start date fo proton therapy
measure: MTV
timeFrame: At inclusion and and 11 months following the start date fo proton therapy
measure: TLG
timeFrame: At inclusion and and 11 months following the start date fo proton therapy
Other outcomes:
Locations:
city: Delft
country: Netherlands
facility: HollandPTC
state: South Holland
city: Leiden
country: Netherlands
facility: LUMC
state: South Holland
Study officials:
affiliation: LUMC/HollandPTC
name: Stijn Krol, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: LUMC
name: Hans Bloem, prof. MD PhD
role: PRINCIPAL_INVESTIGATOR
References: