Imaging NSCLC Treatment Response to Immunotherapy

Imaging NSCLC Treatment Response to Immunotherapy: Relating Inflammatory Activity on 18FDG PET to Tumour Specific Measures From DW-MRI

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).

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Radiation: FDG PET-CT; Other: Imaging - DW-MRI

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.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • The Royal Marsden NHS Foundation Trust

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: Probability Sample

Study Population

The study population includes patients with NSCLC requiring palliative radiotherapy to the chest and for which no curative therapy exists.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in DW-MRI derived ADC	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.	Duration of Study - 2 year
Changes in FDG PET/CT SUV	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.	Duration of Study - 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess for differences in tumour volume using DW-MRI	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.	Duration of Study - 2 year
Assess for differences in tumour volume using 18FDG PET-CT	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.	Duration of Study - 2 year
Assess correlation between DW-MRI derived ADC and FDG PET/CT SUV	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.	Duration of Study - 2 year
Ability to predict progression free time and overall survival using DW-MRI ADC	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.	Duration of Study - 2 year
Ability to predict progression free time and overall survival using 18FDG SUV	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.	Duration of Study - 2 year

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Royal Marsden NHS Foundation Trust; National Institute for Health Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 31, 2016
• Primary Completion (ACTUAL): May 14, 2020
• Study Completion (ACTUAL): May 14, 2020

Study Registration Dates

• First Submitted: April 20, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (ESTIMATE): April 28, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 29, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: PET/CT; non-small cell lung cancer; Magnetic Resonance Imaging
• Other Study ID Numbers: CCR4364