MedPath

Imaging NSCLC Treatment Response to Immunotherapy

Completed
Conditions
Cancer
Registration Number
NCT02753569
Lead Sponsor
Institute of Cancer Research, United Kingdom
Brief Summary

This feasibility study will aim to assess the potential for functional imaging biomarkers (18FDG PET-CT and DW-MRI) to differentiate immunotherapy induced inflammation, indicative of response from non-response in patients with stage IV non-small cell lung cancer (NSCLC).

Detailed Description

30 patients, recruited from within the PEAR Study (Phase 1 dose escalation of palliative radiotherapy with anti-PD1 antibody pembrolizumab in thoracic tumours) will be scanned both before and after receiving immunotherapy for NSCLC. Immunotherapy induced changes in tumour ADC on DW-MRI (a surrogate of apoptotic tumour cell death) will be compared with changes in near contemporaneous, anatomically co-registered 18FDG PET-CT SUV (a non-specific marker for GLUT expression and hence metabolic activity in both tumour and tumour infiltrating lymphocytes). For treatment response, an increase in ADC (reflecting apoptosis within the tumour) is expected, while 18FDG uptake is expected to decrease compared with baseline tumour uptake. In the presence of significant inflammatory cell recruitment, the investigators hypothesise a similar increase in ADC on DW-MRI but without associated reduction in 18FDG PET-CT SUV. Thus the relationship between the ADC change on DW-MRI and the 18FDG change should distinguish between response and non-response in the presence of inflammation.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
Inclusion Criteria
  • Recruited to PEAR: Phase 1 dose escalation of palliative radiotherapy with anti-PD1 antibody pembrolizumab in thoracic tumours Study
Exclusion Criteria
  • MRI incompatible metal implants
  • Claustrophobia

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Changes in FDG PET/CT SUVDuration of Study - 2 year

Describing changes in 18FDG-PET SUV will provide data that may be used to differentiate immune mediated response from non-response in a future study of treatment responses following immunotherapy.

Changes in DW-MRI derived ADCDuration of Study - 2 year

Describing changes in DW-MRI derived ADC will provide data that may be used to differentiate immune mediated response from non-response in a future study of treatment responses following immunotherapy.

Secondary Outcome Measures
NameTimeMethod
Ability to predict progression free time and overall survival using DW-MRI ADCDuration of Study - 2 year

Assess DW-MRI ADC, used alone or in combination with 18FDG SUV (before and after immunotherapy), for its ability to predict progression free and overall survivals following subsequent radiotherapy.

Assess for differences in tumour volume using DW-MRIDuration of Study - 2 year

Assess for differences in tumor volume evaluated using DW-MRI. This will be used as a comparison against other modalities for assessing differences in tumour volume e.g. 18FDG PET-CT. CT is the current standard for radiotherapy target volumes in the chest and with the greater soft tissue delineation facilitated by MRI, comparison of the modalities is warranted.

Assess for differences in tumour volume using 18FDG PET-CTDuration of Study - 2 year

Assess for differences in tumor volume evaluated using 18FDG PET-CT. This will be used as a comparison against other modalities for assessing differences in tumour volume e.g. MRI. CT is the current standard for radiotherapy target volumes in the chest and with the greater soft tissue delineation facilitated by MRI, comparison of the modalities is warranted.

Assess correlation between DW-MRI derived ADC and FDG PET/CT SUVDuration of Study - 2 year

Assess the correlation between 18FDG PET Standardised Uptake Values and DW-MRI derived ADC values. Correlations between ADCmax and SUVmax; ADCmean and SUVmean; plus total lesion ADC and total lesion glycolysis will be explored. Recent reports of imaging biomarkers for defining radiotherapy 'dose painting' schedules have focussed on PET imaging and correlation of these parameters with DW-MRI is not yet established.

Ability to predict progression free time and overall survival using 18FDG SUVDuration of Study - 2 year

Assess 18FDG SUV, used alone or in combination with DW-MRI ADC (before and after immunotherapy), for their ability to predict progression free and overall survivals following subsequent radiotherapy.

Trial Locations

Locations (1)

The Royal Marsden NHS Foundation Trust

🇬🇧

Sutton, Surrey, United Kingdom

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