Leptomeningeal metastases from non-small cell lung cancer: state of the art and recent advances

Pellerino, Alessia; Internò, Valeria; Muscolino, Erminia; Mo, Francesca; Bruno, Francesco; Pronello, Edoardo; Franchino, Federica; Soffietti, Riccardo; Rudà, Roberta

doi:10.20517/2394-4722.2020.80

Cited by 10 publications

(10 citation statements)

References 135 publications

(182 reference statements)

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“…LMC is a life-threatening consequence of solid tumors that has a poor prognosis regardless of treatment ( Pellerino et al, 2020 ). Because effective treatment strategies against primary tumors are developing every day, LMC incidences are increasing ( Lee et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of commonly mutated genes in leptomeningeal carcinomatosis

Congur

Koni

Onat

et al. 2023

PeerJ

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Background Leptomeningeal carcinomatosis (LMC) is a rare type of cancer that settles at the meninges through metastasis of non-small cell lung cancer (NSCLC), breast cancer and melanoma. The molecular mechanism underlying LMC is not known, therefore molecular studies investigating the development of LMC are needed. Here, we aimed to identify commonly mutated genes in LMC caused by NSCLC, breast cancer, and melanoma using an in-slico approach and their interactions using integrated bioinformatic approaches/tools in this meta-analysis. Methods We conducted a meta-analysis using information from 16 studies that included different sequencing techniques of patients with LMC caused by three different primary cancers: breast cancer, NSCLC, and melanoma. All studies that assessed mutation information from patients with LMC were searched in PubMed, from their inception to February, 16 2022. Studies that performed NGS on LMC patients with NSCLC, breast cancer, or melanoma were included, while studies that did not apply NGS to CSF samples, did not provide information on altered genes, were reviews, editorials, or conference abstracts, or whose main goal was the detection of malignancies were all excluded. We identified commonly mutated genes in all three types of cancer. Next, we constructed a protein-protein interaction network, then performed pathway enrichment analysis. We searched National Institutes of Health (NIH) and Drug-Gene Interaction Database (DGIdb) to find candidate drugs. Results We found that TP53, PTEN, PIK3CA, IL7R, and KMT2D genes were commonly mutated genes in all three types of cancer via our meta-analysis that consisted out of 16 studies. Our pathway enrichment analysis showed that all five genes were primarily associated with regulation of cell communication and signaling, and cell proliferation. Other enriched pathways included regulation of apoptotic processes of leukocytes and fibroblasts, macroautophagy and growth. According to our drug search we found candidate drugs; Everolimus, Bevacizumab and Temozolomide, which interact with these five genes. Conclusion In conclusion, a total of 96 mutated genes in LMC were investigated via meta-analysis. Our findings suggested vital roles of TP53, PTEN, PIK3CA, KMT2D, and IL7R, which can provide insight into the molecular basis of LMC development and paving the door to the development of new targeted medicine and will encourage molecular biologists to seek biological evidence.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of commonly mutated genes in leptomeningeal carcinomatosis

Congur

Koni

Onat

et al. 2023

PeerJ

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“…The pathogenesis of LMD in patients with GBM remains unclear.Tumor cells reach and invade leptomeninges in various ways, such as through hematogenous spread, perineural and perivascular lymphatic spread, and direct seeding from the brain parenchyma. [20,21]Direct spread to the CSF space is particularly relevant to primary brain tumors, [22] as tumor contact with the subventricular zone is a known risk factor for LMD. [23]Moreover, tumor cells may disseminate through the CSF with a predilection to regions with slow CSF ow or gravity-dependent sites, such as the basal cisterns or posterior fossa.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Prognosis of Patients with Glioblastoma with Infratentorial Leptomeningeal Dissemination

Kawauchi

Ohno

Honda‐Kitahara

et al. 2022

Preprint

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Objective: Leptomeningeal dissemination (LMD) is a severe complication of glioblastoma (GBM) and has become a more common and indispensable clinical proposition with improved patient prognosis. Although infratentorial leptomeningeal dissemination (ITD) of GBM is rare, it is clinically significant as it may largely influence patient prognosis. Here, we investigated the clinical characteristics and prognosis of patients with ITD.Methods: Data of patients with newly diagnosed isocitrate dehydrogenase (IDH)-wildtype GBM treated at our institution between October 2008 and December 2018 were reviewed. ITD was defined as the dissemination of GBM, which first emerged as a supratentorial tumor, and later disseminated in the infratentorial region as the first recurrent site.Results: Of 160 patients with newly diagnosed IDH-wildtype GBM, seven (4.4%) were classified as having ITD. ITD lesions were in the fourth ventricle in two patients, extra-cerebellum or extra-brainstem in two, and intra-cerebellum in three. The primary symptoms of ITD were gait disturbance (85.7%, n=6), nausea and vomiting (28.6%, n=2), cerebellar mutism (14.3%, n=1), and none (14.3%, n=1). In four cases (57.1%), symptoms were confirmed before ITD discovery.The median progression-free survival (PFS) and overall survival of the patients were 12.2 and 19.7 months, respectively. Radiotherapy was performed in five patients, and all the patients received chemotherapy. The PFS and overall survival rates from ITD diagnosis were 2.9 and 7.1 months, respectively. Patients with favorable prognoses were younger and had higher Karnofsky performance status (KPS) scores.Conclusions: Radiotherapy or molecular-targeted therapy may be effective in some cases of ITD and may contribute to extending survival. Carefully checking the infratentorial region of patients with GBM during follow-up and rapidly treating ITD before their KPS score starts declining are crucial.

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“…The pathogenesis of LMD in patients with GBM remains unclear. Tumor cells reach and invade leptomeninges in various ways, such as through hematogenous spread, perineural and perivascular lymphatic spread, and direct seeding from the brain parenchyma [20,21]. Direct spread to the CSF space is particularly relevant to primary brain tumors [22], as tumor contact with the subventricular zone is a known risk factor for LMD [23].…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognosis of patients with glioblastoma with infratentorial leptomeningeal dissemination

Kawauchi

Ohno

Honda‐Kitahara

et al. 2022

Preprint

View full text Add to dashboard Cite

Objective Leptomeningeal dissemination (LMD) is a severe complication of glioblastoma (GBM) and has become a more common and indispensable clinical proposition with improved patient prognosis. Although infratentorial leptomeningeal dissemination (ITD) of GBM is rare, it is clinically significant as it may largely influence patient prognosis. Here, we investigated the clinical characteristics and prognosis of patients with ITD. Methods Data of patients with newly diagnosed isocitrate dehydrogenase (IDH)-wildtype GBM treated at our institution between October 2008 and December 2018 were reviewed. ITD was defined as the dissemination of GBM, which first emerged as a supratentorial tumor, and later disseminated in the infratentorial region as the first recurrent site. Results Of 160 patients with newly diagnosed IDH-wildtype GBM, seven (4.4%) were classified as having ITD. ITD lesions were in the fourth ventricle in two patients, extra-cerebellum or extra-brainstem in two, and intra-cerebellum in three. The primary symptoms of ITD were gait disturbance (85.7%, n = 6), nausea and vomiting (28.6%, n = 2), cerebellar mutism (14.3%, n = 1), and none (14.3%, n = 1). In four cases (57.1%), symptoms were confirmed before ITD discovery. The median progression-free survival (PFS) and overall survival of the patients were 12.2 and 19.7 months, respectively. Radiotherapy was performed in five patients, and all the patients received chemotherapy. The PFS and overall survival rates from ITD diagnosis were 2.9 and 7.1 months, respectively. Patients with favorable prognoses were younger and had higher Karnofsky performance status (KPS) scores. Conclusions Radiotherapy or molecular-targeted therapy may be effective in some cases of ITD and may contribute to extending survival. Carefully checking the infratentorial region of patients with GBM during follow-up and rapidly treating ITD before their KPS score starts declining are crucial.

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Leptomeningeal metastases from non-small cell lung cancer: state of the art and recent advances

Cited by 10 publications

References 135 publications

Meta-analysis of commonly mutated genes in leptomeningeal carcinomatosis

Meta-analysis of commonly mutated genes in leptomeningeal carcinomatosis

Clinical Characteristics and Prognosis of Patients with Glioblastoma with Infratentorial Leptomeningeal Dissemination

Clinical characteristics and prognosis of patients with glioblastoma with infratentorial leptomeningeal dissemination

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