Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience

Abstract

Objective: Embryonal tumors with multilayered rosettes (ETMRs) are highly aggressive pediatric brain tumors with poor prognosis. No standard treatment strategy for them exists because of their rarity. This study aimed to share experiences on the clinical diagnosis and treatment of ETMRs at China Children’s Medical Center (CCMC). Methods: Patients who received a diagnosis of an ETMR between January 2017 and June 2020 were included. Clinical characteristics, such as age of onset, tumor size, stage, tumor site, treatment strategy, and clinical outcome, were retrospectively analyzed. Results: There were four boys and one girl within 4 years who received a diagnosis during this 4-year timeframe, and were thus included. The average age of morbidity was 29 months (range 16–66 months). The common clinical presentation was headaches and nausea caused by intracranial hypertension. All four patients were chromosome 19 microRNA cluster (C19MC) amplification positive. Two patients achieved complete remission, and one patient attained partial remission after multimodal treatment. Of the two deaths, one died from the rapid progression of the disease and another from tumor-related complications. Conclusion: ETMRs are extremely rare brain tumors with a high, early mortality in children. Surgery is the mainstream treatment for ETMRs. Some patients may also benefit from postoperative adjuvant chemotherapy and radiotherapy.

Embryonal tumor with multilayered rosettes arising from the internal auditory canal of an adult: Illustrative case with molecular investigations

“…Surgery remains the cornerstone of therapy in ETMR to relieve symptoms, improve outcomes, and provide pathological samples, 3 and in this case a total resection of the tumor was achieved. Whole brain and spinal cord radiotherapy was also employed in our management, with retrospective studies indicating early radiotherapy has a positive impact on overall survival with ETMR 7,16 .…”

“…The "CHEMO" regimen of cyclophosphamide, vincristine, etoposide, cisplatin, and high-dose methotrexate induced complete remission in two out of the five ETMR patients included in a case series and partial remission in one other case. 3 Alternatively, the multicenter prospective "P-HIT" study trialed a carboplatin/etoposide induction followed by tandem high-dose chemotherapy involving carboplatin, etoposide, cyclophosphamide, thiotepa, and methotrexate, the so-called CARBO/ETO + HDCT treatment, 19 which resulted in 47% estimated overall survival (OS). Further studies and case reports have described other regimens, mainly based on cyclophosphamide, etoposide, cisplatin, and methotrexate, with mixed results.…”

“…Nonetheless, other studies and case series illustrate some encouraging outcomes using chemoradiotherapy. The “CHEMO” regimen of cyclophosphamide, vincristine, etoposide, cisplatin, and high‐dose methotrexate induced complete remission in two out of the five ETMR patients included in a case series and partial remission in one other case 3 . Alternatively, the multicenter prospective “P‐HIT” study trialed a carboplatin/etoposide induction followed by tandem high‐dose chemotherapy involving carboplatin, etoposide, cyclophosphamide, thiotepa, and methotrexate, the so‐called CARBO/ETO + HDCT treatment, 19 which resulted in 47% estimated overall survival (OS).…”

“…Only around 300 cases of ETMR have been reported worldwide to date, with an estimated incidence in Europe of just 1.35 out of 1 million children aged 1-4 years old. 3 Of these, the majority have been reported to occur in the cerebral hemispheres of infants, with a paucity of ETMR cases reported in adults.…”

“…ETMR have a universally poor prognosis, and their rarity has hindered the development of a standardized treatment protocol or research into new therapies. Only around 300 cases of ETMR have been reported worldwide to date, with an estimated incidence in Europe of just 1.35 out of 1 million children aged 1–4 years old 3 . Of these, the majority have been reported to occur in the cerebral hemispheres of infants, with a paucity of ETMR cases reported in adults.…”