Short summary

SOFT is a prospective, one-armed study exploring the toxicity and effect of a stereotactic ablative radiotherapy treatment strategy in patients with oligometastatic disease in the soft tissue, located in the infra-diaphragmatic region. It offers an MR-linac based SBRT solution, with daily adaption throughout the treatment period. This new technique can potentially allow radiation treatments to be delivered more precisely and accurately than with older treatment techniques. This improvement could help reduce side effects and hopefully improve the chance of controlling the disease. 

Rationale

Advances in systemic and local treatment options for cancer patients have gradually improved survival over the years, despite incurable disease. Evidence of prolonged overall survival after treatment with stereotactic ablative radiotherapy (SBRT) to patients with oligometastatic disease (OMD) have recently been published (OLIGOMEZ- NCT02759783 and SABR-COMET- NCT01446744). These data suggest that local ablative therapy of metastases could improve the systemic control of disease. Local control rates after SBRT generally exceed 80% at 1-year, and low rates of toxicity have been reported, provided strict dose constraints to organs at risk are respected. However, serious toxicities such as radiation-induced myelopathy, perforation, esophageal toxic effects and bone fracture have been reported. New technology facilitates SBRT in high risk anatomical regions. The MR- Linac is a new kind of accelerator, that generates magnetic resonance images continuously and deliver radiation treatment - allowing radiotherapy to be adjusted in real time.

The literature is scarce in respect to the optimal dose fractionation scheme when using SBRT, and the optimal imaging work-up for SBRT and MR-linac based treatment, is not yet clearly defined. Prospective studies are needed to further evaluate efficacy and toxicity risk before we can establish its role as a standard of care. The aim is to document long term follow-up in respect to local progression rate, overall survival, progression-free survival, time to progression outside the radiation field at 1-,2- and 5-years follow-up together with acute and late toxicities. Patient reported outcome will be analyzed as well. We hope to improve the chance of controlling the cancer by more precisely treating the cancer.

Description of the cohort

Patients (men and women) with metastatic disease and with a primary cancer diagnose from a solid tumour are candidates for inclusion. A maximum of 5 metastases in 3 organs are allowed for patients with newly diagnosed disease and patients with recurrent disease. A maximum of 3 metastases are allowed for patients with induced oligometastatic disease (widespread metastatic disease is mostly eradicated by systemic treatment, but drug resistant clones are left behind) and oligoprogressive disease (progression of a limited number of metastatic lesions, while remaining metastases are controlled with systemic therapy). At least one metastasis should be localized in the infra-diaphragmatic soft tissue and suited for SBRT. All metastatic sites should be treated or planned for an ablative strategy (e.g. surgery, SBRT, radiofrequency ablation). 

Data and biological material

Participants will be followed for one year after end of treatment and will hereafter be registered through chart review and routine clinical appointments for up to 5 years. The clinical information registered will include: age, sex, medical and surgery history, allergy, medicine, performance status, objective examination, type of disease, stage, disease localization, type of treatment, details from the radiation treatment plan (e.g. prescription dose to target/organs at risk, size of targets and margins), toxicity assessment, quality-of-life (QOL) questionnaires (EQ-5D), patient-reported outcome questionnaires (PRO-CTCAE), time to disease progression, time to death, blood test results, pathology, and scan results. Blood samples are collected as part of the standard follow-up program. 

Collaborating researchers and departments

Odense University Hospital, Department of Oncology

• Associate professor, MD PhD Tine Schytte
• PhD student, RN MPH Pia Krause Møller

Herlev Hospital, Department of Oncology

• Associate professor, MD PhD Gitte Fredberg Persson  
• Staff Specialist, MD Mette Felter

Rigshospitalet, Department of Oncology

• Consultant, MD PhD Mette Pøhl
• Physicist PhD, Mirjana Josipovic
• Professor, PhD DMSc Ivan Richter Vogelius