Oligometastatic disease

Aim

We to aim provide a platform for treatment of oligometastatic disease across cancer diagnoses to share clinical information regarding definitive local treatment options. We will start a prospective registration study and couple these efforts to different translational research projects.

Background

Historically patients with metastatic cancer are considered incurable and treated with palliative therapies. However, some of these patients have long disease-free survival when treated with definitive treatment to all metastatic sites and the existence of an oligometastatic state between locoregional- and metastatic disease have been proposed. The introduction of targeted therapies and immune checkpoint inhibitors to control micrometastatic disease and precise local therapies lead us to believe that a more aggressive approach to these patients may be meaningful and result in prolonged progression-free survival and even cure in rare cases.

The oligometastatic state is rarely defined further and is likely cancer type dependent and best defined biologically. Most studies have focused on up to five metastases, but some have included patients with up to eight metastases.

Evidence is emerging that definitive treatment of oligometastases may beneficial. Definitive treatment of oligo liver and lung metastases are the standard approach in the treatment of sarcoma, colorectal cancer and is increasingly used for the oligometastatic lung, kidney- and breast cancer.

Definitive treatment of brain-, lung- and liver metastases have proven safe therapeutic strategies. Local treatment of oligometastases in the bone and soft tissues are emerging but further clinical studies are needed.

We propose to set-up a network of treatment options, including several clinical trials to ensure treatment options for patients with oligometastatic disease, within the frame of a prospective open registration study.

Methods

The OLIGO project will include a national survey, a startup workshop, a registration protocol and an umbrella for future studies.

• A national workshop with participants from the different Danish Multidisciplinary Cancer Groups (DMCGs) to establish a steering committee, present the different International efforts (ESTRO/EORTC) and to discuss the national survey and the OLIGO trial in detail.
• A national survey of patterns of care based on questionnaires sent out to all oncology centers in DK regarding which interventional treatment regimens are used. That will include stereotactic radiotherapy, surgery and radio-ablative treatment.
• The OLIGO study. National prospective open registry of patients with oligometastases. Estimated inclusion period will be from 2019-24. All patients with solid tumors with all kinds of oligometastases can be included if treated with local treatments. Systemic treatment is allowed according to the national and institutional guidelines. Primary endpoint is progression-free survival. Secondary endpoints are toxicity, treated lesions specific progression-free survival and overall survival. Patient-, oligometastatic category, tumor- and treatment specific characteristics will be registered. Patients will be followed for 5 years. The registration study will be accompanied by a parallel blood-sampling project to detect circulating tumor-DNA, micro RNA and other inflammatory cytokines.
• Registration of future and ongoing trials on definitive treatment of metastases. So far two studies are hosted by the OLIGO project:
  1. The bone SBRT registry will focus on stereotactic radiotherapy of bone metastases. The specific aim is to enhance quality assurance for a recently introduced treatment, to validate prognostic factors and improve the treatment technique. Data on primary disease, bone metastases characteristic, radiotherapy parameters, toxicity and follow up data for 24 months will be registered.
  2. The ESCABR trial – A phase 1 trial of dose-ESCAlation for stereotactic radiotherapy of surgical cavities after resection of BRain metastases. The aim is to investigate the dose tolerance for hypofractionated stereotactic radiotherapy in resection cavities of brain metastases.
• An OLIGO project homepage with registration of national and local phase I-III studies, as well as, standard definitive treatment of metastases.

Expected results

The OLIGO project will facilitate opportunities for treatment of most metastatic sites and a systematic registration of centers that offers these treatment options. Through the network, we will provide nationwide SBRT quality assurance and tested SBRT regimens for most metastatic sites.  The coupling these efforts with blood samples, pathology and outcome data would provide a better understanding of mechanisms behind treatment resistance and disease progression. The data from the OLIGO study will be used to make a prediction model to predict treatment outcome and form future studies and treatment algorithms.  

Milestones: Year 1: National workshop, national survey, writing of registration protocol, Year 2: start registration protocol, a publication of national survey, webpage up and running, Year 3: Inclusion in registration protocol.

Impact/Relevance/Ethics

This is a high impact project. Patients with metastatic cancer have more treatment options and live longer. The demand for further definitive treatment is increasing and the understanding of cancer as a more chronic disease is evolving. Multimodality treatment combining systemic treatment with definitive local treatment is emerging as a paradigm. Designing a nationwide study across diagnoses with pragmatic and clinical relevant inclusion criteria will give us the statistical strength to gain knowledge on this subset of patients. The study protocols will be submitted to the national ethical committee and the Danish data protection agency.

Clinical trials

• SOFT, ClinicalTrials.gov identifier: NCT04407897
• BONY-M, ClinicalTrials.gov identifier: NCT05101824
• RT-TREAT, ClinicalTrials.gov identifier: NCT05126875
• ESO-SPARE, ClinicalTrials.gov identifier: NCT05109819