Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 17;25(16):8957.
doi: 10.3390/ijms25168957.

Role of Bone Metastases in Lung Neuroendocrine Neoplasms: Clinical Presentation, Treatment and Impact on Prognosis

Roberta Modica  1 , Elio Benevento  1 , Barbara Altieri  2 , Roberto Minotta  1 , Alessia Liccardi  1 , Giuseppe Cannavale  1 , Gianfranco Di Iasi  1 , Annamaria Colao  1   3
Affiliations

Role of Bone Metastases in Lung Neuroendocrine Neoplasms: Clinical Presentation, Treatment and Impact on Prognosis

Roberta Modica et al. Int J Mol Sci. .

Abstract

Lung neuroendocrine neoplasms (L-NEN) are heterogeneous tumors. While bone metastases (BM) have been associated with worse prognosis in other NEN, their role in L-NEN deserves in-depth analysis. This study analyzes the clinical presentation, treatment and survival outcomes of L-NEN, focusing on patients with BM compared with patients without metastases or with metastases in other sites (OtherMtx). The clinicopathological and survival data of L-NEN admitted to the Federico II University were retrospectively evaluated. Fifty L-NEN were included. Among 27 metastatic patients (54%), 13 (26%) had BM, more commonly occurring in males than females and in primary bilateral L-NEN or L-NEN > 26 mm, with higher Ki67. Atypical carcinoid and hypovitaminosis D were associated with BM. The number of metastatic sites was higher in patients with BM than OtherMtx. Synchronous metastases were associated with shorter overall survival (OS). The median progression-free survival (PFS) and OS in patients with BM were similar to OtherMtx, but a two-times increased risk of shorter OS was detected. BM do not impact PFS or OS more than OtherMtx, but the increased risk of shorter OS in patients with BM should be considered. Periodic bone evaluation in L-NEN should be recommended.

Keywords: atypical carcinoid; bone metastases; lung neuroendocrine neoplasm; neuroendocrine; pulmonary NEN; typical carcinoid.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Levels of 25OH-vitamin D at L-NEN diagnosis in patients without metastases (No mtx), with bone metastases (BM) or with metastases in different organs (OtherMtx). Legend: * p < 0.05; the error bars represent minum and maximum value.
Figure 2
Figure 2
(a) Distribution of the samples based on histotype and metastases, with atypical carcinoid incidence being significantly higher in the BM group. (b) Levels of Ki67 in the three groups. Legend: BM: bone metastases; mtx: metastases; ** p < 0.01; the error bars represent minum and maximum value.
Figure 3
Figure 3
(a) Cumulative incidence of metachronous metastases between patients with BM or with OtherMtx. Even if not statistically significant, a trend of OtherMtx towards metachronous metastases could be observed. (b) Number of metastatic sites in patients with BM towards patients with OtherMtx. Legend: BM: bone metastases; mtx: metastases; ** p < 0.01; the error bars represent minum and maximum value.
Figure 4
Figure 4
(a) BM sites. (b) BM characteristics. Legend: BM: bone metastases.
Figure 5
Figure 5
(a) Progression-free survival (PFS) of patients with BM compared with patients with OtherMtx: no difference is observed. (b) Overall survival (OS) of patients with BM compared with patients with OtherMtx: a trend towards a worse OS in BM is observed. Legend: BM: bone metastases; mtx: metastases.
See this image and copyright information in PMC

References

    1. Ruggeri R.M., Benevento E., De Cicco F., Fazzalari B., Guadagno E., Hasballa I., Tarsitano M.G., Isidori A.M., Colao A., Faggiano A. Neuroendocrine Neoplasms in the Context of Inherited Tumor Syndromes: A Reappraisal Focused on Targeted Therapies. J. Endocrinol. Investig. 2023;46:213–234. doi: 10.1007/s40618-022-01905-4. - DOI - PubMed
    1. Modica R., Liccardi A., Minotta R., Cannavale G., Benevento E., Colao A. Current Understanding of Pathogenetic Mechanisms in Neuroendocrine Neoplasms. Expert. Rev. Endocrinol. Metab. 2024;19:49–61. doi: 10.1080/17446651.2023.2279540. - DOI - PubMed
    1. Das S., Dasari A. Epidemiology, Incidence, and Prevalence of Neuroendocrine Neoplasms: Are There Global Differences? Curr. Oncol. Rep. 2021;23:43. doi: 10.1007/s11912-021-01029-7. - DOI - PMC - PubMed
    1. Alsina M., Marcos-Gragera R., Capdevila J., Buxó M., Ortiz R.M., Barretina P., Vilardell L., Brunet J., Beltran M., Izquierdo À. Neuroendocrine Tumors: A Population-Based Study of Incidence and Survival in Girona Province, 1994–2004. Cancer Epidemiol. 2011;35:e49–e54. doi: 10.1016/j.canep.2011.05.011. - DOI - PubMed
    1. Dasari A., Shen C., Halperin D., Zhao B., Zhou S., Xu Y., Shih T., Yao J.C. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States. JAMA Oncol. 2017;3:1335–1342. doi: 10.1001/jamaoncol.2017.0589. - DOI - PMC - PubMed

LinkOut - more resources