Integration of a Personalized Molecular Targeted Therapy into the Multimodal Treatment of Refractory Childhood Embryonal Tumor with Multilayered Rosettes (ETMR)

Hartman, Lisa L.R.; Oaxaca, Derrick M.; Carcamo, Benjamin; Wilson, Harry; Ross, Jeremy A.; Robles-Escajeda, Elisa; Kirken, Robert A.

doi:10.1159/000497380

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…We have previously used molecular genetics to identify a driving metabolic pathway within refractory Inflammatory Myofibroblastic Tumor that was specifically targeted with the TKI Lorlatinib with good response [ 42 ]. We also used proteomics in a refractory childhood embryonal tumor with multilayered rosettes of the brain to identify a driving metabolic pathway that was targeted with the TKI desatinib that and resulted in gross total resection of the tumor and prolong survival [ 43 ]. Unfortunately we have also found that these heavily pretreated tumors frequently become resistant to TKI after a few months of response [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature

Carcamo

Francia

2022

JCM

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We report a retrospective case series of six Hispanic children with tumors treated with metronomic chemotherapy. The six cases comprised one rhabdoid tumor of the kidney, one ependymoma, two medulloblastomas, one neuroblastoma, and a type II neurocytoma of the spine. Treatment included oral cyclophosphamide daily for 21 days alternating with oral etoposide daily for 21 days in a backbone of daily valproic acid and celecoxib. In one case, celecoxib was substituted with sulindac. Of the six patients, three showed complete responses, and all patients showed some response to metronomic therapy with only minor hematologic toxicity. One patient had hemorrhagic gastritis likely associated with NSAIDs while off prophylactic antacids. These data add to a growing body of evidence suggesting that continuous doses of valproic acid and celecoxib coupled with alternating metronomic chemotherapy of agents such as etoposide and cyclophosphamide can produce responses in pediatric tumors relapsing to conventional dose chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature

Carcamo

Francia

2022

JCM

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“…Based on this, an international consensus was developed. The efficacy of personalized molecular targeted therapy for ETMR is also being explored ( 14 ). Proton radiotherapy has a far more adjustable dose distribution than high-energy X-ray radiotherapy, and its Bragg peak can realize the rapid dose drop behind the tumor, which can help protect the organs at risk.…”

Section: Discussionmentioning

confidence: 99%

Ependymoblastoma with pulmonary metastasis in an adolescent: A case report

et al. 2022

Front. Neurol.

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Ependymoblastoma is a rare embryonal neoplasm of the nervous system, and the entity is even rare with distant metastasis. This case can help refine the existing literature and provide lessons for the management of other patients with ependymoblastoma. The present case concerns an adolescent with supratentorial ependymoblastoma, who received gross-total resection (GTR), postoperative radiotherapy, and six cycles of chemotherapy, with disease-free survival (DFS) of about 5.3 years. Subsequently, pulmonary metastasis occurred, but no intracranial lesion was found. Finally, combined treatment with radiotherapy and chemotherapy significantly reduced the lung lesions, with progression-free survival (PFS) of 10 months and long-term survival of 6.3 years. This case indicates that the lung metastases of ependymoblastoma are relatively sensitive to radiation, but lung metastases have not completely disappeared. Perhaps, increasing the radiation dose to lung metastases can improve the efficacy, which is worth exploring.

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“…Currently, molecular-targeted therapy has gradually played an important role in tumor therapy. [6][7][8] However, to date, recognized prognostic markers and potential therapeutic targets for spinal chordoam patients remain limited. 9 Therefore, the determination of key molecules and signaling pathways related to the etiology and pathogenesis of chordoma lays the foundation for the development of new targeted drugs to improve the current treatment of patients with spinal chordoma.…”

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confidence: 99%

“…Therefore minimizing and controlling tumor progression has become important before surgical resection. Currently, molecular-targeted therapy has gradually played an important role in tumor therapy 6–8 . However, to date, recognized prognostic markers and potential therapeutic targets for spinal chordoam patients remain limited 9 .…”

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confidence: 99%

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

He,

Liu

2024

Spine

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Study Design: Retrospective study. Objective: In this study, we explore the potential relationship between HIF-1α and prognosis of patients with spinal chordoma. Summary of Background Data: Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between hypoxia inducible factor1α (HIF-1α) and tumor angiogenesis, metastasis and recurrence have been widely reported, it has been not investigated in the context of spinal chordoma. Methods: In this study, 32 samples of chordoma patients were compared to 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry (IHC). Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1α expression and the clinicopathological characteristics of patients with chordoma was analyzed using Pearson’s chi-square test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders. Results: HIF-1α mainly expressed in the cytoplasm or nucleus in all of the chordoma samples which showed significantly higher than that in the normal nucleus pulposus tissue (P=0.004). Multivariate Cox regression analyses showed that high HIF-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (HR=3.374; P=0.021) and OS (HR=4.511; P=0.012). In addition, we further found that high HIF-1α expression both in cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885; P=0.011) and OS (HR=4.014; P=0.011) in spinal chordoma patients. Conclusion: High HIF-1α expression may become a potential new biological indicator to predict poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.

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Integration of a Personalized Molecular Targeted Therapy into the Multimodal Treatment of Refractory Childhood Embryonal Tumor with Multilayered Rosettes (ETMR)

Cited by 5 publications

References 14 publications

Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature

Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature

Ependymoblastoma with pulmonary metastasis in an adolescent: A case report

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

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