ThOracic Umbrella RadIotherapy STudy in stage IV NSCLC - TOURIST

Background

Non-Small Cell Lung Cancer (NSCLC) is the leading global cause of cancer death with an incidence of >1.2 million; 70% of patients present with incurable disease with treatment aimed at alleviating symptoms, maintaining / improving quality of life (QoL) as well as prolonging survival.

Radiotherapy is widely used in stage IV NSCLC and has proven to be effective in reducing patients’ symptom burden. Current radiotherapy practice is based on data originating from a series of dose-fractionation trials in the 1990s (Stevens R; 2015), when systemic therapy options were limited. Trials tended to focus on patients with locally advanced disease with a predominance of patients with good performance status (PS 0-1).

The last decade has seen major improvements in systemic therapy (chemotherapy, immunotherapy and mutation-targeted tyrosine kinase inhibitors (TKIs)). These improvements mean that systemic therapy is now standard of care for PS 0–2 patients (NICE; 2019) and radiotherapy as a single-modality treatment for less fit patients (PS 2–4). Sadly many patients suffer from loco-regional symptomatic relapse leading to increasing variation in the use of radiotherapy to manage this problem.

The variation seen in palliative thoracic radiotherapy reflects the limited evidence of its use in together with modern systemic treatments and improvements in palliative care and symptom management since the 1990s. It is timely that thoracic radiotherapy benefits are investigated to guide practice over the coming decades. The TOURIST platform aims to use advanced radiotherapy techniques to establish the utility of thoracic radiotherapy in the primary treatment of stage IV NSCLC.

Methods

TOURIST will establish a phase III platform; the two initial studies will cover the needs of differing patient populations, defined by the use of first line systemic therapy.

Study 1 (PRINCE) addresses the addition of early high-dose palliative thoracic radiotherapy in patients receiving standard of care first line systemic treatment to assess if improvement in local control results in improved QoL / survival for patients. 472 participants, recruiting over a 27-month period will be randomised (1:1) at the start of their first-line treatment with Patient Reported Outcome Measures (PROMS) assessing health utilities as the primary outcome. Secondary endpoints include overall survival, progression free survival, lung cancer symptoms and toxicity.

Study 2 (QUARTZ LUNG) Radiotherapy is used as single-modality treatment in the cohort of stage IV patients unsuitable for systemic therapy. This cohort is underrepresented in the 1990s’ dose fractionation studies. This arm seeks to establish the role of low-dose palliative thoracic radiotherapy by applying the methodology developed for the original QUARTZ study (Mulvenna; 2016). 448 participants, recruited over a 42-month period, will be randomised (1:1) to the addition of thoracic radiotherapy to symptomatic palliative care.

Follow up by patient-selected mode will be used for the PROMs data collection and to measure health utility with primary and secondary outcomes as listed above.

An economic evaluation to measure the quality adjusted life years at 21 months (PRINCE) and 6 months (QUARTZ LUNG) will be performed alongside a process evaluation using qualitative methods to identify issues for implementation. Translational studies will be conducted (separate funding streams) focused on tumour biomarker and radiomics.