Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial

Abstract

Background Choroid plexus carcinoma (CPC) is a rare and aggressive tumor of infancy without a clear treatment strategy. This study describes the outcomes of children with CPC treated on the multi-institutional phase 2 SJYC07 trial and reports on the significance of clinical and molecular characteristics. Methods Eligible children <3 years-old with CPC were postoperatively stratified to intermediate-risk (IR) stratum if disease was localized or high-risk (HR) stratum, if metastatic. All received high-dose methotrexate–containing induction chemotherapy. IR-stratum patients received focal irradiation as consolidation whereas HR-stratum patients received additional chemotherapy. Consolidation was followed by oral antiangiogenic maintenance regimen. Survival rates and potential prognostic factors were analyzed. Results Thirteen patients (median age: 1.41 years, range: 0.21–2.93) were enrolled; 5 IR, 8 HR. Gross-total resection or near-total resection was achieved in ten patients and subtotal resection in 3. Seven patients had TP53-mutant tumors, including 4 who were germline carriers. Five patients experienced progression and died of disease; 8 (including 5 HR) are alive without progression. The 5-year progression-free survival (PFS) and overall survival rates were 61.5 ± 13.5% and 68.4 ± 13.1%. Patients with TP53-wild-type tumors had a 5-year PFS of 100% as compared to 28.6 ± 17.1% for TP53-mutant tumors (P = .012). Extent of resection, metastatic status, and use of radiation therapy were not significantly associated with survival. Conclusions Non-myeloablative high-dose methotrexate–containing therapy with maximal surgical resection resulted in long-term PFS in more than half of patients with CPC. TP53-mutational status was the only significant prognostic variable and should form the basis of risk-stratification in future trials.

Final results of the Choroid Plexus Tumor study CPT-SIOP-2000

“…Establishing a treatment algorithm as guidance was a major objective of the CPT-SIOP-2000 study, and the algorithm developed was widely followed in the international pediatric neuro-oncology community. Comparing the overall outcome of this study to the original literature analysis suggests a benefit of a structured algorithm in that the 2-year survival rate in the historical data collection was only half of what was found in CPT-SIOP-2000 [15,19,21,23,25]. Subsequent guidelines were more detailed and included response to treatment and LFS status [28,30].…”

“…A quantitative literature review comparing chemotherapeutic agents suggested benefit of etoposide, carboplatin, cyclophosphamide and vincristine, while similar suggestive evidence was absent for cisplatin, procarbazine and ifosfamide [ 25 ]. Since then, methotrexate has been added to the spectrum [ 19 , 33 , 34 , 37 ]. CPT-SIOP-2000 adds evidence in support of the use of carboplatin (CarbEV) to achieve superior efficacy (significant for PFS, but not OS) compared to cyclophosphamide (CycEV), however the randomization numbers were low.…”

“…Treatment recommendations for CPT include multidisciplinary approaches, with maximal surgical resection for all CPT [8][9][10][11][12][13][14], followed by chemotherapy [11,[15][16][17][18][19][20][21] and radiotherapy [22][23][24] for high-risk CPT. The prognosis of CPC remains dismal when tumor resection is the only treatment modality, and the role, sequence, and intensity of primary chemotherapy remain debatable [13,19,21].…”

Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing

“…Previous studies have demonstrated that the TP53 status is a significant prognostic variable in CPC. Patients with wild-type TP53 treated with high doses of methotrexate presented a 100% 5-yr progression-free survival, compared to only 28.6% in patients with TP53 mutations (Liu et al 2021). This suggests that the TP53 status should be considered in future tumor stratification.…”

Approaches to Minimise the Neurodevelopmental Impact of Choroid Plexus Carcinoma and Its Treatment

“…The third challenge is the historically poor outcome of CPC patients, with the 5-year overall survival (OS) reported to be between 21% and 74% [ 5 , 7 , 15 , 16 , 17 , 18 ]. Physicians have fought for a ‘cure’ at the expense of the ‘cost’ of that cure.…”