The landscape of small cell lung cancer metastases: Organ specificity and timing

Abstract

Background Early metastasis is a hallmark of small cell lung cancer (SCLC). However, the mechanisms and resulting patterns of SCLC dissemination are unclear. Our aim was thus to investigate the organ specificity and timing of blood‐borne metastases in a comprehensive large cohort of SCLC patients. Methods In this retrospective non‐interventional cross‐sectional study of 1009 Caucasian SCLC patients, we investigated the correlation between the distinct locations of the primary tumor and metastatic sites. Results The onset of bone (p < 0.001), brain (p < 0.001), and pericardial (p = 0.02) metastases were late events, whereas adrenal gland (p = 0.005) and liver (p < 0.001) metastases occurred earlier. No significant difference was found in the distribution of early versus late metastases when comparing central and peripheral primary tumors. Patients with bone metastases had a higher than expected likelihood of having liver metastases, while brain metastases tended to appear together with adrenal gland metastases. Pleural and both lung and pericardial metastases also tended to co‐metastasize together more frequently than expected if metastatic events occurred independently. Notably, patients with central primary tumors had decreased median overall survival (OS) compared to those with peripheral tumors, although this tendency does not appear to be significant (p = 0.072). Conclusion Our results are suggestive for particular site‐ and sequence‐specific metastasis patterns in human SCLC. SCLC bone metastases tend to appear together with liver metastases, while brain metastases occur together with adrenal gland metastases. Better understanding of metastasis distribution patterns might help to improve the diagnosis and therapeutic decision‐making in SCLC patients.

Bone-Specific Metastasis Pattern of Advanced-Stage Lung Adenocarcinoma According to the Localization of the Primary Tumor

“…With regards to lung cancer, our group previously found that peripheral LADCs more often give rise to lung metastases whereas skeletal metastases are more common in central tumors ( 7 ). In contrast, the metastasis pattern was not influenced by the bronchoscopic localization of the primary tumor in SCLC patients ( 30 ). In the present study, we found that femoral and rib metastases were more frequently associated with peripheral tumors whereas centrally located LADCs were associated with humeral metastases.…”

“…The impact of primary tumor location on the site preference of organ metastases has been investigated in different solid tumors including non-small cell lung cancer (NSCLC) ( 7 , 28 , 29 ), small cell lung cancer (SCLC) ( 30 ), colorectal‐( 31 – 33 ) and pancreatic cancer ( 34 ). In pancreatic cancer, primary tumors in the pancreatic body or tail correlated with a less aggressive phenotype compared to tumors in the head of the pancreas ( 34 ).…”

Mutational characteristics of bone metastasis of lung cancer

“…Different subtypes of LC have preferential metastatic sites, such as liver metastasis of small cell LC, and brain metastasis of small cell LC and adenocarcinoma (21,22). The percentage of bone metastases in LC patients ranges from 20% to 40% (23).…”

Neuronal mimicry generates an ecosystem critical for brain metastatic growth of SCLC

“…Brain metastases are particularly frequent in SCLC patients (Boire et al, 2020). Up to 15% of patients with SCLC have asymptomatic brain metastases at the time of the first diagnosis, and the incidence increases to 40-60% during the course of the disease (Ko et al, 2021; Megyesfalvi et al, 2021; Rusthoven et al, 2020). Brain metastases contribute so much to the morbidity and mortality of SCLC patients that prophylactic cranial irradiation protocols have been implemented, as even slowing the growth of brain metastases might lead to clinical benefit (Neal et al, 2011; Takahashi et al, 2017).…”