Immunological Function After Radiation With Either Proton or Photon Therapy (PRO-IMMUNO)

Effect of Protons Versus Photons on Immunological Function in Head and Neck Cancer: a Pilot Study

This is a pilot prospective observational cohort study, comprising patients with head and neck cancer (HNSCC) treated with standard of care definitive (chemo)radiation either with photons or protons. Patients will be assigned for protons or photons based on the guidelines of the National Indication Protocol for Proton therapy of the Netherlands.

Immunological function will be evaluated by the collection of peripheral blood mononuclear cells (PBMCs). Blood samples will be collected at baseline, during (chemo)radiation (end of week 3 and/or before week 4 of treatment) and after completion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation). To quantify immunological function, PBMCs collected during (chemo)radiation and after (chemo)radiation will be compared with that before (chemo)radiation (week 0), using IFN-γ-ELISPOT to screen for the presence of antigen-specific T-cell responses. Furthermore, flow cytometry panels will be used to determine global changes in immune cell proficiency.

Histological evaluation will take place at baseline and week 3 to examine changes in immune infiltration within tumour tissue during proton versus photon (chemo)radiation. This biopsy part of the study is optional for the patient. Archival tissue from the biopsy that was taken at diagnosis will be used for the baseline assessments. Biopsy at week 3 week will be taken for all patients who agree to participate in this optional part of the study.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Oropharynx Cancer; Larynx Cancer; HNSCC; Hypopharynx Cancer
• Intervention / Treatment: Other: blood draws

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Tineke Meijer, MD, PhD; Phone Number: 0015 361 6161; Email: t.van.zon@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700 RB
    • Recruiting
    • University Medical Center Groningen (UMCG)
    • Contact: Anneke Eerkens, MSc; Phone Number: 0015 361 6161; Email: a.l.eerkens@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will be recruited at the Univeristy Medical Center Groningen (UMCG( and consists of adult patients recently diagnosed with stage III-IV HNSCC. Both photon and proton radiation are standard-of-care treatments for patients with HNSCC.

Description

Inclusion Criteria:

• Newly diagnosed stage III-IV HNSCC of the oral cavity, oropharynx, hypopharynx or larynx.
• Treatment with definitive (chemo)radiation (70 Gy with or without weekly cisplatin) with photons or protons.
• Age of 18 years and older.
• Elective or therapeutic bilateral neck irradiation indicated.
• Written informed consent according to local guidelines.

Exclusion Criteria:

• Unilateral radiotherapy of the neck.
• (Diagnostic) resection of the primary tumour.
• Chemoradiation with carboplatin and 5-FU or radiation combined with cetuximab.
• History of an autoimmune disease or other systemic intercurrent disease that might affect the immunocompetence of the patient, or current or prior use (4 weeks before start of the trial) of high dose immunosuppressive therapy.
• Additional malignancy that is progressing or has required active treatment within the past 3 years. Note: participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Participation in a study of an investigational agent or has used an investigational device within 4 weeks prior enrolment in this trial. Note: participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Active infection requiring systemic therapy.
• Current pregnancy.
• History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of this trial, interfere with the subject's participation for the full duration of this trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chemoradiation with protons; HNSCC patients treated with standard-of-care chemoradiation with protons.	Other: blood draws; Blood draws to collect PBMCs at baseline (week 0), during (chemo)radiation treatment (end of week 3 and/or before delivery of cycle 4 of cisplatin) and after conclusion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation) in order to compare immunological function upon treatment with either protons or photons
Chemoradiation with photons; HNSCC patients treated with standard-of-care chemoradiation with photons.	Other: blood draws; Blood draws to collect PBMCs at baseline (week 0), during (chemo)radiation treatment (end of week 3 and/or before delivery of cycle 4 of cisplatin) and after conclusion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation) in order to compare immunological function upon treatment with either protons or photons
Radiation with protons; HNSCC patients treated with standard-of-care radiation with protons.	Other: blood draws; Blood draws to collect PBMCs at baseline (week 0), during (chemo)radiation treatment (end of week 3 and/or before delivery of cycle 4 of cisplatin) and after conclusion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation) in order to compare immunological function upon treatment with either protons or photons
Radiation with photons; HNSCC patients treated with standard-of-care radiation with photons.	Other: blood draws; Blood draws to collect PBMCs at baseline (week 0), during (chemo)radiation treatment (end of week 3 and/or before delivery of cycle 4 of cisplatin) and after conclusion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation) in order to compare immunological function upon treatment with either protons or photons

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in antigen-specific immunity in HNSCC patients undergoing (chemo)radiation with protons versus photons.	Antigen-specific immunity will be assessed by monitoring antigen-specific T-cell responses in peripheral blood before, during and after (chemo)radiation (up to 12 months after completion of (chemo)radiation) to viral peptides such as SARS-CoV-2 peptides and CEF peptides (CMV, EBV and Influenza).	At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in composition and function of circulating immune cells during and after (chemo)radiation with protons versus photons.	Differences in composition and function of circulating immune cells will be determined by flow cytometry-based assays using marker for e.g. T- and B-lymphocytes and different myeloid cells such as derived suppressor cells.	At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)
Immune infiltrate composition within the primary tumour tissue before and during (chemo)radiation with photons versus protons (optional part of the study).	Immunohistological staining will be performed on these tumour tissues to assess changes in the composition of immune cells after (chemo)radiation with protons versus photons These assays include molecular analyses and immunohistochemical staining to characterize the type of the intratumoral immune cell infiltrate. In particular, immunohistochemical staining to identify immune cell populations and T cell subpopulations within the tumour tissue can be applied, including, but not limited to, CD4, CD8, FoxP3, CD20, CD163, CD68, PDL1 and PD1. Both changes in absolute numbers and ratios of different immune cell types will be assessed.	At baseline (week 0) and during (chemo)radiation (week 3)

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2021
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms
• Other Study ID Numbers: NL75013.042.20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No