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Optimising Cancer Therapy And Identifying Causes of Pneumonitis USing Artificial Intelligence (COVID-19)

Completed
Conditions
Lung Cancer
Covid19
Pneumonitis
Interventions
Diagnostic Test: Machine Learning Classification of parenchymal lung change cause
Diagnostic Test: Machine Learning Classification of recurrence and non-recurrence
Registration Number
NCT04721444
Lead Sponsor
Royal Marsden NHS Foundation Trust
Brief Summary

Distinguishing changes on patients that have received thoracic radiotherapy and patients that are currently receiving or have recently received IO and presenting lung changes which will be identified using AI.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1211
Inclusion Criteria

Cohort A1 (from Arm A) - Immunotherapy (IO) pneumonitis cases: patients currently on or having received ICI IO in the last 3 months of presentation with:

• New radiological lung changes on CT/CXR (confirmed on report) of a severity and distribution consistent with IO pneumonitis. These changes should be of severity and distribution that are not incompatible with viral or lower respiratory tract infection.

AND Must not have had RT involving the thorax (unless this was breast/chest wall RT more than 5 years ago, which is permissible) AND

  • Where there is documented clinical concern for infection, have undergone one or more laboratory investigations for viral or lower respiratory tract infection including, but not limited to Nasopharyngeal aspirate or swab for respiratory virus by PCR; Sputum sample or bronchial washings MCS with no organism(s) consistent with lower respiratory tract infection, cytology or beta-glucan/galactomannan for PCP or fungal infection; broncho-alveolar lavage for markers of infection such as MCS, PCR, fungal culture, beta-glucan/galactomannan for PCP or evidence of lower respiratory tract infection (including invasive fungal infection) by cytology, none of which were considered positive for infection by the clinical team.
  • Where empirical antibiotics were prescribed, patients must either have had a negative BAL infection screen or may be included at the discretion of the local site PI and local radiologist with lung interest or two members of the trial management group, one of whom must be a radiologist with lung interest or respiratory physician or oncologist with suitable experience of thoracic CT imaging, after after review of the case-notes.
  • Prophylactic co-trimoxazole prescribed in the context of high-dose steroid therapy is permitted.

Cohort A2 (from Arm B) - Radiotherapy (RT) pneumonits cases: Patients that have completed a course of RT involving the thorax (e.g. lung, breast, oesophageal RT) in the last 12 months prior to presentation, that have not received immunotherapy, with:.

• New radiological lung changes on CT/CXR (confirmed on report) of a severity and distribution consistent with radiation pneumonitis or early fibrosis (should not include established fibrosis). These changes should be of severity and distribution that are not incompatible with viral or lower respiratory tract infection.

AND

  • Where there is documented clinical concern for infection, have undergone one or more laboratory investigations for viral or lower respiratory tract infection including, but not limited to Nasopharyngeal aspirate or swab for respiratory virus by PCR; Sputum sample or bronchial washings MCS with no organism(s) consistent with lower respiratory tract infection, cytology or beta-glucan/galactomannan for PCP or fungal infection; broncho-alveolar lavage (BAL) for markers of infection such as MCS, PCR, fungal culture, beta-glucan/galactomannan for Pneumocystis Pneumonia (PCP) or evidence of lower respiratory tract infection (including invasive fungal infection) by cytology, none of which were considered positive for infection by the clinical team. Where empirical antibiotics were prescribed, patients must either have had a negative BAL infection screen or may be included at the discretion of the local site PI and local radiologist with lung interest or two members of the trial management group, one of whom must be a radiologist with lung interest or respiratory physician or oncologist with suitable experience of thoracic CT imaging, after review of the case-notes.
  • Prophylactic co-trimoxazole prescribed in the context of high-dose steroid therapy is permitted.

B1 (Utilised in Arms A & B) Non-COVID-19 infective cases:

  • New radiological lung changes on CT/CXR (confirmed on report) of a severity and distribution consistent with lower respiratory tract infection but compatible with the grade and nature of pneumonitis seen with IO or RT
  • AND
  • Laboratory findings that fulfil one or more of the following criteria of infection: Nasopharyngeal aspirate or swab positive for a respiratory virus by PCR; Sputum sample or bronchial washings positive MCS for an organism(s) consistent with lower respiratory tract infection, cytology or beta-glucan/galactomannan positive for PCP or fungal infection, positive urine legionella/pneumococcal antigen screen, positive serology for mycoplasma pneumonia; broncho-alveolar lavage for markers of infection (MCS, PCR, fungal culture, beta-glucan/galactomannan for PCP or other evidence of lower respiratory tract infection (including invasive fungal infection) by cytology. Where no such laboratory findings were positive but the patient improved with anti-microbial therapy, such cases may be included at the discretion of the local site PI and local radiologist with lung interest or two members of the trial management group two members of the trial management group, one of whom must be a radiologist with a lung interest or respiratory physician or oncologist with suitable experience of thoracic CT imaging, after review of the case-notes and imaging.
  • Not previously treated with immunotherapy OR
  • Must not have had RT involving the thorax (unless this was breast/chest wall RT more than 5 years ago, which is permissible)
  • First assessed prior to 1st January 2020 (and therefore not attributable to COVID-19)

B2 (Utilised in Arms A & B) COVID-19 cases:

• Laboratory findings that fulfil one or more of the following criteria of COVID-19 infection: positive COVID-19 PCR test and/or antigen test or other suitable assay that indicates current infection or previous exposure (including serology tests) as determined by the trial management group (TMG).

AND

  • New radiological lung changes on CT/CXR (confirmed on report) of a severity and distribution consistent with COVID-19. These changes should be of severity and distribution that is not incompatible with the grade of pneumonitis seen with IO or RT
  • Not previously treated with immunotherapy OR
  • Must not have had RT involving the thorax (unless this was breast/chest wall RT more than 5 years ago, which is permissible)
  • Assessed after 1st January 2020 (and therefore contemporaneous with COVID-19)
Exclusion Criteria

• Patients with documented past medical history of congestive cardiac failure or other cause for interstitial lung disease

Arm C:

Inclusion Criteria:

  • Adult patients (aged 18 or over) treated with radical thoracic RT (conventional fractionated RT +/- chemotherapy or SBRT) for NSCLC
  • RT planning scan imaging and labelled structure set data available from participating centre
  • Minimum 2 years of post-RT follow-up data including clinical or histological confirmation in the case of recurrence and whether the patient is alive as available from primary care or hospital records.
  • Patients with post-treatment surveillance CT imaging (minimum of first scan post-treatment and where available +/- further scans within 2 years post-RT, e.g. at 3/6/12 months post-treatment).

Exclusion Criteria:

  • Any patient that does not have a primary lung mass e.g. Tx disease
  • Any patient being treated for recurrence of a previously treated lung cancer
  • Any patient that did not have radical RT e.g. patients that had high dose palliative RT
  • Any patient that does not have imaging that meets technical requirements within the imaging processing and analysis manual

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Arm A - Test Cohort (Cohort C1)Machine Learning Classification of parenchymal lung change causeTest set C1: Patients on IO and with possible toxicity versus COVID-19 or other infective pneumonitis
Arms A and B - Cohort B1Machine Learning Classification of parenchymal lung change causeTraining set B1: IO and RT naive and pneumonia (without COVID-19)
Arm A - Cohort A1Machine Learning Classification of parenchymal lung change causeTraining set: Pneumonitis in the context of IO therapy and negative for infectious pneumonia (including COVID-19)
Arms A and B - Cohort B2Machine Learning Classification of parenchymal lung change causeTraining set B2: IO and RT naive and confirmed COVID-19 positive with pneumonia
Arm B - Test Cohort (Cohort C2)Machine Learning Classification of parenchymal lung change causeTest set C2: Patients with pneumonitis in context of thoracic RT with possible toxicity versus COVID-19 or other infective pneumonitis.
Arm B - Cohort A2Machine Learning Classification of parenchymal lung change causeTraining set: Pneumonitis in the context of thoracic RT and negative for infectious pneumonia (including COVID-19)
Arm CMachine Learning Classification of recurrence and non-recurrencePatients with radiotherapy planning CT scans and post-treatment surveillance CT scans at 3, 6 and 12-months post treatment
Primary Outcome Measures
NameTimeMethod
Development of a Machine Learning model to distinguish parenchymal lung changes3 years

The development and validation of an ML/radiomic classifier to distinguish between Infective/COVID-19 pneumonia and cancer therapy induced lung changes

Development of a Machine Learning model to predict recurrence risk after radical radiotherapy for non-small cell lung cancer3 years

to develop a prognostic AI/radiomic signature for NSCLC recurrence after radical RT (Conventional fractionated RT +/- chemotherapy or stereotactic body RT (SBRT)) to stratify appropriate surveillance and onward care, thus minimising unnecessary hospital visits and resource use.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (3)

Imperial College Healthcare NHS Trust

🇬🇧

London, United Kingdom

Guys and St. Thomas' NHS Foundation Trust

🇬🇧

London, United Kingdom

Royal Marsden NHS Foundation Trust

🇬🇧

London, United Kingdom

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