Role of Local Treatment for Oligometastasis: A Comparability Based Meta-Analysis

Recent evidence supports the role of aggressive local treatment in the oligometastatic setting.In this review, we discuss the top 10 lessons we have learned from trials in oligometastatic cancers. Major lessons learned pertain to definitions of oligometastatic disease, outcomes, toxicity, costs, and the combination of ablative therapies with systemic therapy, including immunotherapy. Barriers to accrual for trials and upcoming phase III trials are also reviewed.These lessons may help to inform clinical practice and may be the basis for future research in the oligometastatic space.

Section: Lesson #1: There May Never Be An Exact Cut-off For What Cons...mentioning

confidence: 99%

Section: Lesson #3: In Choosing a Treatment Modality The Evidence Bes...mentioning

confidence: 99%

Top Ten Lessons Learned from Trials in Oligometastatic Cancers

Tan

Palma

2023

“…However, there are still no clinically biomarkers or other techniques to identify oligometastasis that can distinguish the real oligometastatic state from a rapidly of oligometastatic NSCLC and elucidating its potential difference from the polymetastasis will enable a more thorough selection of patients with a low metastatic burden in whom local radical treatment integrated into multimodality regime can be applied to all metastatic sites. Systemic therapies, including targeted therapies and immunotherapy, combined with local treatments such as surgery, stereotactic ablative radiotherapy or thermal ablation can indeed obtain a long-term survival with promising progression-free survival (PFS) or overall survival (OS) [6][7][8][9] in oligometastatic NSCLC. Previous researches on actionable genomic alterations for targeted therapies and predictive biomarkers of immunotherapy mainly focused on populations of conventional NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non–Small Cell Lung Cancer

Liao¹,

Chen²,

Li³

et al. 2023

Oligometastatic non-small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome.However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and MethodsWe performed next-generation sequencing (NGS) to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. ResultsWe found ERBB2, ALK, MLL4, PIK3CB and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden (TMB) of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair (DDR) genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion A c c e p t e d A r t i c l eCANCER RESEARCH AND TREATMENT (CRT) 3

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confidence: 99%

Oligometastasis: More Lessons to Be Learned

Kim¹,

Ahn²

2023

Self Cite

The first use the term "oligometastasis' in the literature was done by Hellman and Weichselbaum, who also built its concept as "the status between localized and widely metastatic" [1]. Though not all previous trials that evaluated the role of local aggressive treatment (LAT) in oligometastatic settings were affirmative, it cannot be denied that LAT has a strong tendency of improving clinical outcomes, which was elucidated through the effort of Oligometastasis Working Group of Korea Cancer Association [2]. As the meaning of the prefix "oligo-", with Latin origin, contains "few, small, or little" in number, the definition of oligometastasis has mostly been based on the metastatic lesion number, and most clinical trials, in fact, have adopted the number-based definition. The metastatic state, however, is more of a spectrum from none to numerous, and an exact cut-off number defining the oligometastatic status [3].In this issue, Tan and Palma [4] summarized "10 lessons learned from clinical trials on oligometastasis", and suggested that, instead of the metastatic lesion number per se, the possibility of benefit to the patients by applying LAT should be more importantly considered. Since there should have existed a few practical limitations in counting the actual metastatic lesion number even with the most up-to-date diagnostic imaging studies. There has been no single perfect imaging modality, and all have varying ranges of false-negative and false-positive rates in almost all real-world clinical situations. The usually proposed numbers, therefore, are not the absolute criteria with "all or none" magic, but could usually serve as the useful guidance to the clinicians who encounter some important decision points. One of the extreme example has been elucidated in the National Comprehensive Cancer Network guideline for the management of metastatic brain tumors [5], in which the "limited metastasis" has been defined mainly based on the applicability of radiosurgery instead of whole-brain radiation therapy, while notwithstanding the number of metastatic lesions detected. In addition, shortly following the acceptance of Tan and Palma's review article on our journal, a substudy of the SABR-COMET-10 trial [6], ongoing randomized phase 3 trial that intends to assess the stereotactic ablative radiation therapy (SABR) effect in the patients having 4 to 10 metastatic lesions, was published. These authors have already started recruiting the patients with larger lesion number than the previously reports, which limitedly recruited those with 3 or 5 lesions [7-9], and found that the planning outcomes of the first 60 patients were within minimal compromise of dose constraints. This could serve another endorsement to the Tan and Palma's speculation. The simple counting the metastatic lesion number may not have as great critical significance when compared with the past era. This trend of broader criteria of oligometastasis may have been possible in close relation with the wide availability of highly reliable, safe, and effective LAT mod...