The Impact of Radiotherapy on Oligometastatic Cancer

Study Overview
=================
Brief Summary
-----------------
Metastases represent the most threatening challenge in cancer. One of the management strategies for patients with Oligometastatic Cancer (OC) is Stereotactic ABlative Radiotherapy (SABR). However, there are few studies, and there is no defined clinical standard, nor are the radiobiological mechanisms that contribute to treatment response well understood. The focus should be on generating evidence to guide the personalization of radiotherapy beyond solely technological and anatomical precision. This could be achieved by recollecting clinical and biological data from patients that undergo this treatment and analyzing them to ultimately predict, with the help of artificial intelligence, which patients will be the most beneficiary and improve their survival rate.

Detailed Description
-----------------
Metastases are the most threatening challenge in cancer. In patients with metastatic cancer, local radiotherapy treatment remains an essential tool with different goals that depend on numerous factors, especially on the number and extent of the metastases and whether disease control is feasible and desirable according to the expected quality of life. Oligometastatic Cancer (OC), i.e., a few metastases in a few organs, has been recently incorporated as a less aggressive state than widely disseminated metastatic disease. Consequently, OC is a serious candidate for aggressive treatments based on Stereotactic ABlative Radiotherapy (SABR). This treatment has shown promising results and is already incorporated into habitual clinical practices. However, OC is a complex and heterogeneous disease, and not all patients have improved their life quality and expectation. Identifying patients who would benefit from this treatment is an important area of research that needs factual information from a large sample provided by multiple centers. Therefore, this multicenter, retrospective, prospective, observational, and longitudinal study incorporates clinical data, medical images, and biological samples to feed artificial intelligence algorithms. The objective is to determine which patient profile achieves complete response after SABR. The secondary objectives are: To analyze metastases by radiomics using computed tomography, magnetic resonance, or positron emission tomography images; and To evaluate intratumoral metabolites released into circulation by multi-omics analyses. These will contribute to determining the systemic molecular effects of treatment in search of biomarkers with predictive value. Centralized storage of patient management data, clinical image analysis, and candidate biomarkers measured in blood samples may eventually meet the expectations of integrating data into clinical decision-making and influence evolution based on precision medicine.

Official Title
-----------------
Stereotactic ABlative Radiotherapy (SABR) in Oligometastatic Cancer (OC): a Radiomics, Multi-omics, and Machine Learning Approach to Clinical Decision-making. The OC-SABR Multicentric Project

Conditions
-----------------
Metastasis, Metastatic Breast Cancer, Metastatic Prostate Cancer, Metastatic Colorectal Cancer, Metastatic Lung Cancer

Intervention / Treatment
-----------------
* Diagnostic Test: To propose a diagnostic test to determine the viability of Stereotactic ABlative Radiotherapy (SABR).
* Diagnostic Test: To propose a diagnostic test to determine the effectiveness of SABR.
* Diagnostic Test: To propose a diagnostic test for Oligometastatic Cancer (OC).


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic confirmation of primary tumor: breast, prostate, lung, colorectal. 18 years old or older. Up to five metastases located in the bone, lung, node, liver or brain. Eastern Cooperative Oncology Group (ECOG) Performance Status Scale 0 or 1. Exclusion Criteria: Non-melanoma skin cancer. Previous radiotherapy in the same anatomic location. Presence of vascular collagen disease. Pregnancy or lactation at the time of inclusion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| OC-SABR<br>Patients diagnosed with Oligometastatic Cancer (OC) that will receive Stereotactic ABlative Radiotherapy (SABR) that has been prescribed per clinical protocol. | Diagnostic Test: To propose a diagnostic test to determine the viability of Stereotactic ABlative Radiotherapy (SABR).<br>* Analyze clinical data, medical images and molecular circulating features to propose which variables serve to select the patients that will achieve complete response after SABR.<br>Diagnostic Test: To propose a diagnostic test to determine the effectiveness of SABR.<br>* Collect blood samples at five different time points before and after treatment and analyze circulating tumoral DNA, medical images, and metabolites to monitor the effect of SABR and its effectiveness.<br>Diagnostic Test: To propose a diagnostic test for Oligometastatic Cancer (OC).<br>* Analyze circulating tumoral DNA and metabolites from blood samples in search of the profile of OC.<br>|
| Controls<br>Individuals who have never been diagnosed with cancer or oligometastasis. | Diagnostic Test: To propose a diagnostic test for Oligometastatic Cancer (OC).<br>* Analyze circulating tumoral DNA and metabolites from blood samples in search of the profile of OC.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological rate | Images obtained by computerized tomography, magnetic resonance and positron emission tomography serve to evaluate the local control and response rate by: Complete response: absence of disease. Stable disease: no changes. Partial response: 50% or more injury reduction. Progression: 25% or more tumor size increase. According to RECIST Criteria 1.1 and PERCIST. | 3 months after treatment | 
| Progression-Free Survival | To assess the impact of SABR on the progression over time, precisely at 1, 2, 3, and 5 years, regarding Progression-Free Survival (PFS) based on RECIST Criteria 1.1 and PERCIST. | 5 years after treatment | 
| SABR toxicities | To evaluate the progression of SABR toxicities over time, precisely at 1, 2, 3, and 5 years, according to the CTCAE 4.0 scale. | 5 years after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metastasis, Radiosurgery, Metabolomics, Radiomics, Multi-omics, Molecular subtypes