Patient case: 52-year-old male with Colon cancer. Genetic variant: KRAS (G13D), BRAF (V600E). Other conditions: Type II Diabetes, Hypertension.

Clinical trial: COLLISION Trial - Colorectal Liver Metastases: Surgery vs Thermal Ablation

Summary: The primary objective is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable colorectal liver metastases (≤3cm) and no extrahepatic disease.

Detailed description: Study design:
  COLLISION is a single-blind prospective multi-center phase-III randomized controlled trial. We hypothesize that thermal ablation is non-inferior to surgery for the selected patient groups in terms of the primary objective (overall survival). The Cox proportional hazards model (1-sided; non-inferiority or superiority) is used for sample size calculations. Given the superior safety profile we consider a hazard ratio of 1.3 to represent the upper limit of non-inferiority (non-inferiority margin). An HR of 1.3 corresponds to a 56.5% chance of the ablated patients to die first ((P = HR/(1 + HR) = 1.3/(1 + 1.3) = 0.565 (56.5%)). With 3 years of patient accrual and five years of follow-up we will have reached 60% of events (death) in approximately 6.5 years (overall probability of event, pE =0.6). The calculated sample size therefore is 599 (NS).To account for a 10% drop-out ratio (NDO=69) prior to randomization and a 3% loss to follow-up (NLTFU=18) after randomization we need to include 687 patients (NI). A total number of 618 patients will be randomized (NR) into one of two arms: arm A will undergo surgical resection (n=309) and arm B thermal ablation (n=309) for appointed target lesions.
  Study population:
  Patients with ≥1 resectable and ablatable CRLM (≤3cm), no extrahepatic disease, a good performance status (WHO 0-2) and a low-risk clinical risk score (CRS 0-2) are considered eligible. Supplementary resections for resectable lesions >3cm and thermal ablations for unresectable CRLM ≤3cm are allowed with a maximum number of CRLM of 10.
  Intervention:
  Eligible patients will be stratified into low-, intermediate- and high disease burden after assessment by an expert panel. The panel, consisting of at least two diagnostic radiologists, two interventional radiologists and two hepatobiliary and/or oncological surgeons, will appoint lesions that are resectable and ablatable as target lesions, resectable and unablatable lesions as unablatable lesions and ablatable but unresectable lesions as unresectable lesions. All unablatable lesions should be resectable and all unresectable lesions should be ≤3cm and ablatable.
  With the exception of patients that are suitable for laparoscopic resection or percutaneous ablation (low disease burden), eligibility needs to be reconfirmed during the surgical procedure. Hereafter patients will be randomized to undergo surgical resection of the target lesions (allowing thermal ablation for additional unresectable lesions) or thermal ablation (allowing resection for additional unablatable lesions). Patients will remain unaware of the appointed treatment arm and the actual treatment of their target lesions (single-blind). Postprocedural care will be identical between the two groups with the exemption that hepatic recurrences (either local site recurrence or new lesions) suitable for both resection and ablation will again be treated with the technique used to treat the initial target lesion(s). Conferring to national guidelines follow-up will include contrast-enhanced (ce) CT scans, 18F-FDG-PET-CT scans, laboratory tests including tumor markers (CEA) and quality of life questionnaires. Patients with recurrences that are considered unsuitable for additional focal therapy will be re-referred to their medical oncologist to assess additional systemic chemotherapy. In the event of chemotherapeutic down-staging hereafter, focal therapy can be reconsidered.

Eligibility: Participant inclusion criteria, some examples:
  -  Age above 18 years
  -  Life expectancy of at least 12 weeks
  -  Adequate blood samples
  -  Written informed consent
  -  Histological documentation of primary colorectal tumor
  Participant exclusion criteria, some examples:
  -  No target lesions suitable for both resection and ablation
  -  The presence of extrahepatic nodal or non-nodal metastases
  -  Pregnant or breast-feeding subjects
  -  Other therapy given/done prior to the procedure

Relevance to patient case: not relevant