CUratively Intended Thoracic REirradiation: An Observational Study of High-dose Reirradiation of Thoracic Tumours: A Multicentre Prospective Registration Protocol
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University of Aarhus
- Enrollment
- 500
- Locations
- 1
- Primary Endpoint
- Toxicity grade 4-5
Study Overview
Brief Summary
The number of long-term lung cancer (LC) survivors increases, however many patients are diagnosed with recurrent or new thoracic cancers. High-dose reirradiation (reRT) is promising but associated with high severe toxicity rates. Existing studies are small lacking high-quality data, with no clear correlation between toxicity risk and delivered radiotherapy (RT) dose.
This Danish multicentre prospective cohort study aims to provide a framework for collecting radiotherapy-related toxicity data, loco-regional control, and overall survival data for patients with thoracic cancer undergoing reirradiation; with the ultimate aim of providing safe reirradiation to more patients.
As a secondary aim, guidelines for dose accumulation and provisional constraints for the organs at risk will be used to establish a uniform treatment strategy for reirradiation.
The CURE Lung trial will provide high-impact, globally missing data. This project will ensure full utilization of and learning from the trial, adding SDM, PROMs, and modality referral to the trial. It will model the correlation between toxicity burden and doses, enabling individualized reRT with optimized dose prescription based on toxicity risk and patient preferences, and assisting in the decision-making on the prescription dose and optimal modality. This will ensure safe reRT for the increasing number of long-term LC survivors.
Detailed Description
- BACKGROUND:
The number of long-term survivors is increasing for thoracic cancers, however, a significant proportion of lung cancer (LC) patients treated with curatively intended radiotherapy (RT) may experience locoregional recurrence or develop a new cancer. This highlights the need for effective local treatment options. Repeated high-dose RT (reRT) is a promising approach gaining traction in clinical practice. At Aarhus University Hospital (AUH), the fraction of LC patients offered curative reRT has increased from 4% in 2015 to 13% in 2024. The overall survival (OS) of reirradiated recurrent or new LC range from 7-14 months (from time of reirradiation) and depends on a variety of parameters, including tumour dose and PTV volume. ReRT has been linked to high rates of severe toxicity, leading to some patients not being offered curative reRT. Establishing solid evidence of the risks associated with reRT is crucial to offering these patients reRT on an equal footing with patients treated for their first cancer. Former studies on reRT of LC include a median of 40 (maximum 102) patients16, with diverse results on OS and no clear correlations between toxicity risk and cumulative (summed) RT doses. 2. AIM:
Establish a framework for LC reRT based on data from CURE Lung to support clinical and shared decision-making (SDM). Four sub-studies obtain this:
2.1 Establish a national infrastructure for reRT and implement decision-making tools to guide patient referrals to specialised modalities like proton therapy and MR-linac, ensuring optimal treatment modality selection to reRT for the individual patient.
2.2 Integrate and analyse Patient Reported Outcome Measures (PROM), Quality of Life (QoL), and decision regret data in CURE Lung. Mapping of the patient's self-reported symptoms and correlation to toxicity data ensures an optimal overview of total disease burden and informs which patients are candidates for reRT.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Radiotherapy of thoracic lesion(s) (loco-regional lung cancer recurrence, new primary lung cancer, or solitary oligo metastasis) with the aim of long-term local control.
- •Reirradiation type 1 or type 2, i.e. previous radiotherapy to the thorax as per ESTRO-EORTC consensus definition of reirradiation [Andratschke 2022]. For the sake of this study, multiple treatments to the lungs will be classified as type 2 reirradiation.
- •Verification of malignancy based on biopsy. If no biopsy is available, the decision of reirradiation should be agreed upon in a multidisciplinary conference.
- •Available digital dose plan(s) from former radiotherapy course(s) (DICOM files) - note that multiple re-treatments are allowed.
- •Adequate lung function to tolerate treatment, at the discretion of the treating physician.
- •Ability to complete a radiotherapy course with the aim of local control.
- •ECOG Performance status 0-
- •Estimated life expectancy ≥ 6 months
- •Age ≥18 years
- •Signed informed consent
Exclusion Criteria
- •Uncontrolled other malignancy.
- •The primary and the reirradiation treatment may not be quasi-simultaneous (i.e. the two treatments should be planned independently)
- •Pregnancy
- •Radiotherapy to a minimum CTV mean dose of 45 Gy for SCLC and 50 Gy for NSCLC and oligometastatic lesions. Treatment schedule according to local protocols and treating physician preference.
Arms & Interventions
Patients with thoracic cancer elegible for reirradation.
Recurrent lung cancer, new primary lung cancer, solitary lung metastasis
Intervention: Radiotherapy (Radiation)
Outcomes
Primary Outcomes
Toxicity grade 4-5
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Radiotherapy-related toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) grade 4 - 5 one year after start of radiotherapy
Secondary Outcomes
- Late radiotherapy-related toxicity grade 3 - 5(From 6 months after the start of reirradiation and through study completion, assessed up to 60 months)
- Overall survival(From date of enrollment until the date of documented death)
- Decision regret according to the Ottawa Hospital scale(Baseline, at 3 months, and each year through study completion)
- Freedom from progressive disease(From date of enrollment until the date of documented progression)
- Patterns of failure(From date of enrollment until the date of documented recurrence)
- Acute radiotherapy-related toxicity grade 2 - 5(Up to 6 months from the start of reirradiation)
- Radiotherapy treatment compliance(Through study completion, assessed up to 60 months)
- Quality of Life (QoL)(Baseline, at 3 months, and each year through study completion)
- Patient reported outcome measures (PROM)(Baseline, at 3 months, and each year through study completion)