Background/Aim: Interstitial brachytherapy (iBT) seems to achieve higher local tumor control rates for lesions limited in size. The objective was to evaluate the efficacy and safety of iBT in the treatment of limited and large liver metastases from rare or less common cancers (RLCC). Patients and Methods: A total of 194 unresectable liver metastases categorized as limited (<4 cm, n=153, subgroup A) and large lesions (≥4 cm, n=41, subgroup B) were treated. Clinical and image-based follow-up was conducted every 3 months after iBT. Results: Cumulative local recurrence (CLR) rate was 9.8% (19 recurrences; A: n=16; B: n=3). No significant difference in CLR was noted between subgroup A and B (A:10.5%, B:7.3%, p=0.339). Median follow-up was 6.2 months (range=2.2-92.9 months). Complication assessment revealed 5 severe adverse events (grade 3: 4.3%, grade 4 and 5: 0%) with 4 events in A and 1 event in B. Conclusion: IBT is a feasible, effective, and safe minimally invasive treatment for small and large liver metastases from RLCC.According to the RARECAREnet project, rare cancers belong to a defined group of diseases with an incidence rate of <6/100,000, whereas less common cancers could be defined by an incidence of ≥6/1,000,000 outside the common or frequent cancers, such as breast, colorectal, lung and prostate (1, 2). Taken together, these two groups of neoplasms add up to 47% of all newly diagnosed malignancies (2). Since treatment experience is limited even in major cancer centers, rare or less common cancers (RLCC) are a significant challenge to clinical practice with varying survival rates among European countries (3). In particular, developing adequately powered clinical trials for advanced-stage cancer is demanding due to the low number of patients; therefore, evidence for effectiveness of new therapeutic methods is difficult to provide, leading to limited therapy options. Hence, for advanced/metastasized RLCC, research is frequently confined to case reports or small retrospective series.From a theoretical oncological perspective, metastases limited in number and distribution (i.e. oligometastases) are increasingly considered suitable for localized therapy aiming for disease control and prolongation of life in selected patients, as shown for colorectal cancer (CRC). In fact, for CRC patients with oligometastatic disease (OMD) confined to one organ, i.e. most commonly the liver, 5-year survival rates of 25-40% are reported after complete metastasectomy, furthermore, after a survival of 10 years post-surgery, patients are even considered cured (4-6). However, effective surgical resection is applicable to a limited number of cases, as the ability to perform complete macro-and microscopic resection of multiple liver metastases relies on the capacity of the future liver remnant to minimize the risk of posthepatectomy liver failure. Resectability is limited by the distribution and accessibility of metastases, consequently, curative resection of liver metastases is not possible in up to 80% of CRC patients (7).However, ...