Introduction: Subependymal giant cell astrocytoma (SEGA) is the most common CNS tumor in patients with tuberous sclerosis complex (TSC). Although these are benign, their proximity to the foramen of Monroe frequently causes obstructive hydrocephalus, a potentially fatal complication. Open surgical resection has been the mainstay of treatment; however, this can cause significant morbidity. The development of mTOR inhibitors has changed the treatment landscape, but there are limitations to their use. Laser interstitial thermal therapy (LITT) is an emerging treatment modality that has shown promise in treatment of a variety of intracranial lesions, including SEGAs. We present a single institution, retrospective study of patients treated for SEGAs with LITT, open resection, mTOR inhibitors, or a combination of these modalities. The primary study outcome was tumor volume at most recent follow-up compared with volume at treatment initiation. The secondary outcome was clinical complications associated with treatment modality.
Methods: Retrospective chart review was performed to identify patients with SEGAs treated at our institution from 2010 to 2021. Demographics, treatment information, and complications were collected from the medical record. Tumor volumes were calculated from imaging obtained at initiation of treatment and at most recent follow-up. Kruskal-Wallis nonparametric testing was used to assess differences in tumor volume and follow-up duration between groups.
Results: Four patients underwent LITT (3 with LITT only), three underwent open surgical resection, and four were treated with mTOR inhibitors only. Mean percent tumor volume reduction for each group was 48.6 ± 13.8, 90.7 ± 39.8, and 67.1 ± 17.2%, respectively. No statistically significant difference was identified comparing percent tumor volume reduction between the three groups (p = 0.0513). Additionally, there was no statistically significant difference in follow-up duration between groups (p = 0.223). Only 1 patient in our series required permanent CSF diversion and 4 discontinued or decreased the dose of mTOR inhibitor due to either cost or side effects.
Conclusions: Our study suggests that LITT could be considered as a treatment option for SEGAs as it was effective in reducing tumor volume with very few complications. This modality is less invasive than open resection and may be an alternative for patients who are not candidates for mTOR inhibitors. We recommend an updated paradigm for SEGA treatment which includes LITT in select cases after consideration of patient-specific factors.
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http://dx.doi.org/10.1159/000531210 | DOI Listing |
Cancers (Basel)
December 2024
Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Brown University Health, Providence, RI 02903, USA.
In hormone receptor-positive and HER2-negative breast cancers, a growing number of revolutionary personalized therapies are in clinical use or trials, such as CDK4/6 inhibitors, immune checkpoint inhibitors, and PIK3CA inhibitors. Those treatment options are largely driven by the presence or absence of genomic alterations in the tumor. Therefore, molecular profiling is often performed during disease progression.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Sarcoma Unit, The Royal Marsden Hospital and Institute of Cancer Research, London SW3 6JZ, UK.
There has been noteworthy progress in molecular characterisation and therapeutics in soft tissue sarcomas. Novel agents have gained regulatory approval by the FDA. Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Purpose: Ovarian clear cell carcinoma is a highly malignant gynecological tumor characterized by a high rate of chemotherapy resistance and poor prognosis. The PI3K/AKT/mTOR pathway is well-known to be closely related to the progression of various malignancies, and recent studies have indicated that this pathway may play a critical role in the progression and worsening of OCCC.
Methods: In this study, we investigated the combined effects of WX390, a dual inhibitor of PI3K/mTOR, and cisplatin on OCCC through both in vitro and in vivo experiments to further elucidate their therapeutic effects.
Int J Oncol
February 2025
Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, 6229HX Maastricht, The Netherlands.
Human papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in , loss of or activation of receptor tyrosine kinases. In HPV‑negative tumors, (encoding p16 protein) inactivation or (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines.
View Article and Find Full Text PDFNat Commun
January 2025
NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Mutations in RAS and PI3Kα are major drivers of human cancer. Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway. Disrupting RAS-PI3Kα interaction enhances survival in lung and skin cancer models and reduces tumor growth and angiogenesis, although the structural details of this interaction remain unclear.
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