Skip to main content
Download PDF

Impact of radiation response on survival in pediatric medulloblastoma with residual or disseminated disease

Radiation Oncology volume 20, Article number: 52 (2025) Cite this article

Abstract

Background

This study aimed to determine the clinical impact of radiation response on survival in patients with medulloblastoma (MB) and to explore the predictive factor of radiation response.

Methods

Data from 170 pediatric patients with MB and residual disease or metastasis before radiotherapy (RT) were analyzed.

Results

The median follow-up period was 5.2 years. A total of 74 (43.5%) patients achieved CR, 85 (50.0%) patients achieved PR, 8 (4.7%) patients had SD, and 3 (1.8%) patients developed PD after RT. The five-year post-RT progression-free (prtPFS) and overall survival (prtOS) were superior in patients who achieved CR compared to those who did not (prtPFS: 67% ± 6% vs. 42% ± 6%, P < 0.001; prtOS: 82% ± 5% vs. 44% ± 6%, P < 0.001). Multivariable logistic regression analysis showed that residual disease site was the predictive factor for radiation response, patients who had residual disease in both the brain and spinal cord before RT had higher non-CR rate (OR: 7.312, 95%CI 3.375–15.845, P < 0.001). Multivariate Cox analysis revealed that radiation response and large cell/anaplastic subtype were independent prognostic factors for survival (P < 0.05).

Conclusions

Radiation response was an independent prognostic factor for survival in patients with MB. Patients who did not achieve CR after RT should receive intensified adjuvant chemotherapy to improve survival.

Background

Medulloblastoma (MB) is the most prevalent intracranial embryonal tumor in pediatric patients, exhibiting notable heterogeneity [1, 2]. The current standard of care for children over the age of three is a maximum safe excision of the tumor, followed by craniospinal irradiation (CSI) and adjuvant chemotherapy [3]. A multidisciplinary approach to treatment has led to a considerable increase in the long-term survival of patients with MB. Patients in the standard-risk (SR) group have achieved a 5-year overall survival (OS) rate of over 75%, while the prognosis for patients in the high-risk (HR) group, particularly those with residual disease and metastases, remains unsatisfactory [4,5,6]. The clinical outcome of MB is highly dependent on the efficacy of radiotherapy (RT). Omission of RT is associated with an unacceptable neuraxial failure even in patients with the best prognosis [7, 8]. However, few studies have reported the clinical impact of radiation response on survival in patients with MB especially those with residual disease prior to RT [9]. In this study, we retrospectively evaluated a cohort of 170 patients with MB who had measurable residual disease and/or metastases before RT to assess the impact of radiation response on prognosis. On the other hand, we explored the risk factors predicting radiation response.

Methods

Patient cohort

This retrospective study included all consecutive MB patients with residual disease (> 1.5 cm2 of enhancing lesion present at the primary site) or disseminated lesions (M2/3) or both who received RT at Xinhua Hospital between 2009 and 2022. Baseline assessments were conducted via cranial and spinal MRI scans prior to the initiation of RT. The irradiation volume encompassed CSI with a boost to the tumor bed or whole posterior fossa (WPF). The gross tumor volume (GTV) was defined as the initial extent of disease before surgery or any other treatment. The GTV was extended by 1–1.5 cm in all directions to define the clinical target volume (CTV) that included all risk areas for microscopic disease as indicated by surgical reports and pathological examinations, taking into account anatomical constraints. The planning target volume (PTV) consisted of a geometric extension (0.3–0.5 cm) of the CTV to account for setup error or patient movement and was intended to be covered by the 95% isodose line. The CSI doses ranged from 23.4 Gy to 40 Gy (median 36 Gy), delivered in 1.8–2.0 Gy per fraction. Patients who were treated prior to April 2016 underwent RT using intensity modulated radiation (IMRT), while those treated subsequently received treatment using the helical Tomo-therapy. Cranial and spinal MRI scans were reperformed within 3 days after the end of RT and every three months thereafter for the initial two years, every six months during years three to five, and annually thereafter. The therapeutic effect was classified as complete response (CR) or non-CR (including partial response (PR), stable disease (SD), and progressive disease (PD)) according to the RAPNO (Response Assessment in Pediatric Neuro-Oncology) criteria [10]. Alkylator and platinum-based adjuvant chemotherapy was administered at our hospital or at an external facility after RT. Vincristine was used for concomitant chemotherapy. Patients younger than 3 years at diagnosis received chemotherapy first to delay RT and reduce long-term toxicity. Patients who had severe postoperative complications and could not tolerate CSI also received chemotherapy first. The patients’ survival status was followed up by telephone, with the endpoint of follow-ups occurring in October 2024.

Acute hematologic toxicity

Blood cell data were collected retrospectively from complete blood counts performed before and weekly during RT. Average blood cell counts were used when more than one complete blood count was performed in each week. The Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE5) was used to grade hematologic toxicities.

Statistical analysis

Overall survival was defined as the time interval between the end of RT and death from any cause, or the date of the last follow-up (prtOS). Progression free survival was defined as the time interval starting from the end of RT to the date of disease progression or last follow-up (prtPFS). Survival analyses were performed using the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards models. Multivariable logistic regression analyses were used to explore the factors predicting radiation response. Statistical evaluations were performed using SPSS version 23.0 software, and a P-value of less than 0.05 was considered statistically significant.

Results

Clinicopathologic characteristics

The clinicopathological characteristics of the cohort are summarized in Table 1. Of the 170 patients, 106 (62.4%) patients were male; 141 (82.9%) patients were older than 3 years of age at diagnosis; 122 (71.8%) patients had metastatic disease at diagnosis; Most of the tumors (45.3%) were classic histological subtypes and non-WNT/non-SHH molecular subtypes occupied the major types in patients with molecular evidence. All patients had residual diseases before RT and the residual lesions were distributed in the brain (32.9%), spinal cord (19.4%) or both (47.6%).

Treatment characteristics

A total of 35 (20.6%) patients received chemotherapy prior to RT, 11 (6.5%) patients had concurrent chemotherapy. IMRT was employed in 33 (19.4%) cases, while Tomo-therapy was utilized in 137 (80.6%) cases. The median dose of CSI was 36 Gy (range 23.4–40 Gy, only one patient received 23.4 Gy CSI), and the median dose of boost was 54 Gy (range 52.2–57.6 Gy). 74 (43.5%) patients achieved CR, 85 (50.0%) patients achieved PR, 8 (4.7%) patients exhibited SD, and 3 (1.8%) patients developed PD after RT.

Survival and prognostic factors

The median follow-up period after the end of RT for survivors (n = 107) was 5.2 years (range: 0.5–14.8 years). During the observational period of the study, 71 (41.8%) patients suffered disease progression at a median time of 12.0 months after RT. Among these patients, 50 individuals still demonstrated residual disease after RT, with 17 cases occurring in the brain, 10 cases in the spinal cord, and 23 cases involving both the brain and spinal cord. A total of 63 (37.1%) patients died. Of these, 60 patients died due to tumor-related causes, 2 patients died due to severe pneumonia and 1 patient died due to intracranial hypertension without disease progression. For the entire cohort, the 5-year prtPFS and prtOS were 57% ± 4.0% and 60% ± 4%, respectively. In the univariate Cox analyses, patients with residual disease in both brain and spinal cord before RT (P = 0.006) and non-CR after RT (P = 0.001) were associated with poorer prtPFS. Large cell/anaplastic subtype (P = 0.042), metastases (P = 0.045), residual disease in both brain and spinal cord before RT (P = 0.001) and non-CR after RT (P < 0.001) were associated with poorer prtOS (Table 2; Fig. 1). Gender, age at diagnosis, pre-RT chemotherapy, concurrent chemotherapy, radiotherapy mode and radiotherapy dose had no significant difference on prognosis. Forward stepwise multivariate Cox analysis revealed that non-CR after RT (HR, 2.204; 95% CI, 1.222–3.974; P = 0.009) was an independent adverse prognostic factor for prtPFS. Furthermore, non-CR after RT (HR, 3.596; 95% CI, 1.722–7.662; P < 0.001) and large cell/anaplastic subtype (HR, 3.180; 95% CI, 1.104–9.163; P = 0.032) were adverse prognostic factors for prtOS (Table 3).

Fig. 1
figure 1

Patient outcomes after RT for medulloblastoma with residual or dissimilated diseases. The prtPFS for patients achieved CR and non-CR after RT (A), metastatic status at diagnosis (B), residual disease site before RT (C) and histological subtype (D). The prtOS for patients achieved CR and non-CR after RT (E), metastatic status at diagnosis (F), residual disease site before RT (G) and histological subtype (H)

Full size image

The 5-year prtPFS for patients who achieved CR after RT was significantly higher than those who did not achieve CR (67% ± 6% vs. 42% ± 6%, P < 0.001). Similarly, the five-year prtOS was also superior in the CR group (82% ± 5% vs. 44% ± 6%, P < 0.001). Subsequently, the demographic and clinical characteristics of the two sub-cohorts with disparate radiation responses were compared (Table 4). A greater proportion of patients in the non-CR group had metastasis at diagnosis compared to the CR group (81.2% vs. 59.5%). Similarly, a greater proportion of patients in the non-CR group had residual diseases in both the brain and spinal cord before RT (67.7% vs. 21.6%). In univariable logistic regression analyses, patients with stage M+ (OR, 2.955; 95%CI, 1.480–5.899, P = 0.002) and residual diseases in both sites (OR, 7.312; 95%CI, 3.375–15.845, P < 0.001) were associated with non-CR. No significant differences were observed in the distribution of patients regarding gender, age, histology, concurrent chemotherapy, or RT mode. In multivariable analyses, the residual diseases site prior to RT was the independent predictor of radiation response in both the all-inclusive model and forward-stepwise models (Table 5). Patients with residual disease in both brain and spinal cord exhibited a higher likelihood of having non-CR after RT.

With the development of genomics, molecular typing of medulloblastoma has received increasing attention. Molecular typing became popular in our center after 2017, and 91 out of 170 patients had molecular subgroup based on targeted mutation and CNV analysis (n = 61) or NanoString gene expression assay (n = 30) in our study. We then collected molecular information, including MYC or MYCN amplification status, CNV profiles (event number ≥ 5), and integrated these molecular data into our statistical analysis to evaluate their impact on radiation response and prognosis. The results showed that patients with 17p loss (P < 0.001) and MYC amplification (P = 0.051) had poor prtPFS compared to wild-type patients, whereas patients with 7p gain (P = 0.024), 7q gain (P = 0.094) and 17p gain (P = 0.067) had good prtPFS compared to wild-type patients (Table S1). While none of the molecular characteristics can predict the radiation response (Table S2).

Hematologic toxicity

Hematologic toxicity is a well-documented adverse effect of CSI. Our analysis of hematologic data during RT in 158 patients revealed that most patients exhibited grade 3 leukopenia, grade 3 neutropenia, grade 1 anemia, grade 0 thrombocytopenia and grade 4 lymphopenia (Table 6). No patients died because of hematologic toxicity during RT.

Several studies have indicated that RT-associated lymphopenia is associated with poorer clinical outcomes in patients with solid tumors [11,12,13,14]. Subsequently, we explored the dynamic change of lymphocyte during RT. As shown in Fig. 2, the median baseline absolute lymphocyte count (ALC) prior to RT was 1.5 × 109/L (range 0.56–3.52), and no patient had grade 3/4 lymphopenia. In comparison to the baseline, the ALC exhibited a notable decline during the initial three weeks of RT, with a median ALC of 0.61 × 109/L (range 0.18–4.06), 0.32 × 109/L (range 0.13–2.32), and 0.25 × 109/L (range 0.08-3.00), respectively. The ALC ceased its decline from the fourth week of RT and recovered to 0.48 × 109/L (range 0.09–2.61) at the seventh week of RT. Accordingly, the proportion of grade 3/4 lymphopenia in our cohort exhibited a notable increase during the initial four-week period, followed by a gradual decline during the subsequent treatment phase. The ALC exhibited no significant difference between the CR and non-CR groups during RT, while the ALC nadir was observed to be higher in patients who achieved CR (0.19 ± 0.13) ×109/L compared to those who did not (0.15 ± 0.07) ×109/L (t = 2.445, P = 0.016) (Supplementary Fig. S1). Patients were divided into two groups according to the median ALC nadir. There was no significant difference in survival between the two groups (Supplementary Fig. S2).

Fig. 2
figure 2

Lymphocyte count and lymphopenia during RT. (A) The average absolute lymphocyte count (ALC) during RT, (B) the incidence of lymphopenia during RT

Full size image

Discussion

The current standard of care for MB includes initial surgery followed by a combination of radiation and chemotherapy. Despite advances in systemic therapy and neurosurgical techniques, radiation therapy remains essential. Omission of upfront CSI or radiation is associated with unacceptable neuraxial failure, even in low-risk WNT MB with the best prognosis [7, 8]. Here, we provided the real-word data of MB, analyzed the clinical characteristics of patients with residual or disseminated disease before RT and evaluated the effect of radiation response on prognosis. A total of 170 patients were enrolled in the study, and the 5-year prtPFS and prtOS were 57% and 60%, respectively, for the entire cohort. These results are comparable to those of previous studies [15,16,17,18,19].

A series of studies have been conducted to assess the efficacy of postoperative neoadjuvant chemotherapy before RT in patients with high-risk MB, while the results are controversial. The SIOP/UKCCSG PNET-3 study involved the administration of two courses of chemotherapy, comprising vincristine, etoposide, carboplatin, and cyclophosphamide, followed by CSI of 35 Gy and a posterior fossa boost of 20 Gy. With a median follow-up period of 7.2 years, the 5-year EFS rate was 34.7%, and the 5-year overall survival OS rate was 43.9%. There was no apparent improvement in outcome for M2-3 patients undergoing pre-RT chemotherapy [17]. Kortmann et al. performed a prospective, multicenter, randomized trial by using postoperative neoadjuvant chemotherapy before RT to improve survival of patients with MB. However, the results demonstrated that the RT first group exhibited superior outcomes compared to the neoadjuvant chemotherapy group, particularly in patients between 3 and 5.9 years of age [20]. Postoperative neoadjuvant chemotherapy was usually accompanied by increased myelotoxicity of the subsequent RT and lead to a higher rate of interruptions and delayed RT which have a negative impact on outcome. The long-term outcome of the study also corroborated the excellent results in post-RT chemotherapy group compared with the neoadjuvant chemotherapy group [21]. In the prospective multicenter trial HIT 2000, intensified neoadjuvant induction chemotherapy, hyperfractionated CSI and additional four cycles of maintenance chemotherapy were used in patients with metastatic MB. In comparison to the HIT 91 trial, the HIT 2000 trial demonstrated superior OS and comparable EFS although the study did not further explore the impact of RT timing on survival [6]. In another randomized study, POG 9031, patients with high-risk MB were assigned to receive either chemotherapy before RT or chemotherapy after RT. The 5-year EFS and 5-year OS did not exhibit a statistically significant difference between the two groups, but RT first group achieved higher objective response rate than chemotherapy fist group (86% vs. 66%, P = 0.01) [22]. In our study, 79.4% of patients received post-operative RT directly. The prognoses of the RT first group and the chemotherapy first group were found to be similar. Moreover, the objective response rate in our study exceeded 90%, which is higher than that observed in previous studies, may be attributed to the high dose of radiation therapy administered. Subgroup analysis revealed that the radiation response is an independent prognostic factor. Patients who achieved CR after RT exhibited a higher survival rate than those who did not achieve CR. Patients who still had residual disease after RT may require intensified adjuvant chemotherapy to improve survival. Admittedly, intensive treatment may lead to increased treatment-related toxicity [23], and the balance between treatment efficacy and treatment toxicity is an issue that needs to be further explored in the future.

In this study, we also explore the factors affecting radiation response. Multivariable logistic regression analyses indicated that the site of residual disease before RT was associated with radiation response. Patients with residual disease in both the brain and spinal cord had the lowest CR rate and the worst prognosis compared with the other two groups, which may be due to the high tumor burden. Concurrent chemotherapy is common practice in brain tumor, employed with the objective of sensitizing RT and improving survival [24]. In this study, a limited number of patients received concurrent chemotherapy, with the primary chemotherapy agent being vincristine. No significant difference in survival was observed between the patients who received concurrent chemotherapy and those who did not. In a previous study, Liu et al. found that the use of chemotherapy during CSI or the choice of alkylator had no significant impact on patient outcomes [18]. Jakacki and colleagues evaluated the feasibility of administering carboplatin as a radiosensitizer during CSI and proposed that the use of carboplatin represents a promising strategy for patients with metastasis [25]. A subsequent randomized clinical trial demonstrated that intensifying therapy with carboplatin only improved the survival of Group 3 patients [5]. For patients falling into other molecular subgroups, it would be beneficial to explore new radiosensitizers.

Hematologic toxicity is the most common acute toxicity during RT. Patients with high-risk MB usually receive high dose of CSI and the hematologic toxicity is usually obvious. In this study, the grade 3–4 hematologic toxicities are leukopenia, neutropenia and lymphopenia, which are comparable to the previous study [14, 26]. Even through ALC nadir did not prove an effective predictor of prognosis in patients with MB, those with a high ALC nadir demonstrated a higher CR rate. Consequently, strategies to mitigate the risk of radiation-induced lymphopenia warrant consideration.

Conclusions

In conclusion, we summarized the clinical characteristics of MB with residual or disseminated disease before RT and evaluated the effect of radiation response on prognosis. Radiation response is an independent prognostic factor for patients with MB. Patients who achieved CR after RT had higher prtPFS and prtOS compared to those who did not. Patients with residual disease in both the brain and spinal cord exhibited a poorer CR rate and prognosis and may should receive intensified adjuvant chemotherapy. Admittedly, the relatively short follow-up period and the retrospective nature of the study are limitations of the analysis. A prospective randomized study with a long follow-up period is needed for further confirmation.

Table 1 The clinicopathological characteristics of the entire cohort
Full size table
Table 2 Univariate Cox analyses of prognostic factors of survival
Full size table
Table 3 Multivariate Cox analyses of prognostic factors of survival
Full size table
Table 4 Clinical and pathologic characteristics of the two sub-cohorts with different radiation response
Full size table
Table 5 Multivariable logistic regression analysis of predictors of RT response
Full size table
Table 6 Grades of acute hematologic toxicity during radiotherapy
Full size table

Data availability

All data generated and analyzed during this study are available from the corresponding author on request.

Abbreviations

MB:

Medulloblastoma

CSI:

Craniospinal irradiation

SR:

Standard-risk

HR:

High-risk

GTV:

Gross tumor volume

CTV:

Clinical target volume

PTV:

Planning target volume

IMRT:

Intensity modulated radiation

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

prtPFS:

Post-radiotherapy progression-free survival

prtOS:

Post-radiotherapy overall survival

ALC:

Absolute lymphocyte count

References

  1. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united States in 2012–2016. Neuro Oncol. 2019;21(Suppl 5):v1–100. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/neuonc/noz150.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jackson K, Packer RJ. Recent advances in pediatric Medulloblastoma. Curr Neurol Neurosci Rep. 2023;23(12):841–8. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s11910-023-01316-9.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Baliga S, Gandola L, Timmermann B, Gail H, Padovani L, Janssens GO, et al. Brain tumors: Medulloblastoma, ATRT, ependymoma. Pediatr Blood Cancer. 2021;68(Suppl 2):e28395. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/pbc.28395.

    Article  PubMed  Google Scholar 

  4. Salloum R, Chen Y, Yasui Y, Packer R, Leisenring W, Wells E, et al. Late morbidity and mortality among Medulloblastoma survivors diagnosed across three decades: A report from the childhood cancer survivor study. J Clin Oncol. 2019;37(9):731–40. https://doiorg.publicaciones.saludcastillayleon.es/10.1200/jco.18.00969.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Leary SES, Packer RJ, Li Y, Billups CA, Smith KS, Jaju A, et al. Efficacy of carboplatin and isotretinoin in children with High-risk Medulloblastoma: A randomized clinical trial from the children’s oncology group. JAMA Oncol. 2021;7(9):1313–21. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jamaoncol.2021.2224.

    Article  PubMed  PubMed Central  Google Scholar 

  6. von Bueren AO, Kortmann R-D, von Hoff K, Friedrich C, Mynarek M, Müller K, et al. Treatment of children and adolescents with metastatic Medulloblastoma and prognostic relevance of clinical and biologic parameters. J Clin Oncol. 2016;34(34):4151–60. https://doiorg.publicaciones.saludcastillayleon.es/10.1200/jco.2016.67.2428.

    Article  CAS  Google Scholar 

  7. Gupta T, Pervez S, Dasgupta A, Chatterjee A, Epari S, Chinnaswamy G, et al. Omission of upfront craniospinal irradiation in patients with Low-Risk WNT-Pathway Medulloblastoma is associated with unacceptably high risk of neuraxial failure. Clin Cancer Res. 2022;28(19):4180–5. https://doiorg.publicaciones.saludcastillayleon.es/10.1158/1078-0432.Ccr-22-0758.

    Article  CAS  PubMed  Google Scholar 

  8. Cohen KJ, Munjapara V, Aguilera D, Castellino RC, Stapleton SL, Landi D, et al. A pilot study omitting radiation in the treatment of children with newly diagnosed Wnt-Activated Medulloblastoma. Clin Cancer Res. 2023;29(24):5031–7. https://doiorg.publicaciones.saludcastillayleon.es/10.1158/1078-0432.Ccr-23-0348.

    Article  CAS  PubMed  Google Scholar 

  9. Massimino M, Barretta F, Dossena C, Minasi S, Buttarelli FR, Biassoni V, et al. Long-term outcome of the Milano-hyperfractionated accelerated radiotherapy strategy for high-risk Medulloblastoma, including the impact of molecular subtype. Neurooncology. 2025;27(1):209–18. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/neuonc/noae189.

    Article  Google Scholar 

  10. Warren KE, Vezina G, Poussaint TY, Warmuth-Metz M, Chamberlain MC, Packer RJ, et al. Response assessment in Medulloblastoma and leptomeningeal seeding tumors: recommendations from the response assessment in pediatric Neuro-Oncology committee. Neuro Oncol. 2018;20(1):13–23. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/neuonc/nox087.

    Article  CAS  PubMed  Google Scholar 

  11. Lee BM, Byun HK, Seong J. Significance of lymphocyte recovery from treatment-related lymphopenia in locally advanced pancreatic cancer. Radiother Oncol. 2020;151:82–7. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.radonc.2020.07.026.

    Article  PubMed  Google Scholar 

  12. Liu H, Wang H, Wu J, Wang Y, Zhao L, Li G, et al. Lymphocyte nadir predicts tumor response and survival in locally advanced rectal cancer after neoadjuvant chemoradiotherapy: Immunologic relevance. Radiother Oncol. 2019;131:52–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.radonc.2018.12.001.

    Article  PubMed  Google Scholar 

  13. Xie X, Gong S, Jin H, Yang P, Xu T, Cai Y, et al. Radiation-induced lymphopenia correlates with survival in nasopharyngeal carcinoma: impact of treatment modality and the baseline lymphocyte count. Radiat Oncol. 2020;15(1). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-020-01494-7.

  14. Grassberger C, Shinnick D, Yeap BY, Tracy M, Hess SGE. Circulating lymphocyte counts early during radiation therapy are associated with recurrence in pediatric Medulloblastoma. Int J Radiat Oncol Biol Phys. 2021;110(4):1044–52. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ijrobp.2021.01.035.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Allen J, Donahue B, Mehta M, Miller DC, Rorke LB, Jakacki R, et al. A phase II study of preradiotherapy chemotherapy followed by hyperfractionated radiotherapy for newly diagnosed high-risk Medulloblastoma/primitive neuroectodermal tumor: a report from the children’s oncology group (CCG 9931). Int J Radiat Oncol Biol Phys. 2009;74(4):1006–11. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ijrobp.2008.09.019.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Taylor RE, Howman AJ, Wheatley K, Brogden EE, Large B, Gibson MJ, et al. Hyperfractionated accelerated radiotherapy (HART) with maintenance chemotherapy for metastatic (M1–3) Medulloblastoma– A safety/feasibility study. Radiother Oncol. 2014;111(1):41–6. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.radonc.2014.01.022.

    Article  PubMed  Google Scholar 

  17. Taylor RE, Bailey CC, Robinson KJ, Weston CL, Walker DA, Ellison D, et al. Outcome for patients with metastatic (M2–3) Medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer. 2005;41(5):727–34. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ejca.2004.12.017.

    Article  CAS  PubMed  Google Scholar 

  18. Liu AP, Zhen Z, Yang Q, Yuan X, Ma X, Chen J, et al. Treatment barriers and clinical outcome of children with Medulloblastoma in China: a report from the Chinese children’s cancer group (CCCG). Neurooncol Adv. 2021;3(1):vdab134. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/noajnl/vdab134.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed Medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006;7(10):813–20. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s1470-2045(06)70867-1.

    Article  PubMed  Google Scholar 

  20. Kortmann RD, Kühl J, Timmermann B, Mittler U, Urban C, Budach V, et al. Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of Medulloblastoma in childhood: results of the German prospective randomized trial HIT ‘91. Int J Radiat Oncol Biol Phys. 2000;46(2):269–79. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s0360-3016(99)00369-7.

    Article  CAS  PubMed  Google Scholar 

  21. Hoff Kv, Hinkes B, Gerber NU, Deinlein F, Mittler U, Urban C, et al. Long-term outcome and clinical prognostic factors in children with Medulloblastoma treated in the prospective randomised multicentre trial HIT‘91. Eur J Cancer. 2009;45(7):1209–17. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ejca.2009.01.015.

    Article  PubMed  Google Scholar 

  22. Tarbell NJ, Friedman H, Polkinghorn WR, Yock T, Zhou T, Chen Z, et al. High-risk Medulloblastoma: a pediatric oncology group randomized trial of chemotherapy before or after radiation therapy (POG 9031). J Clin Oncol. 2013;31(23):2936–41. https://doiorg.publicaciones.saludcastillayleon.es/10.1200/jco.2012.43.9984.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lee JW, Lim DH, Sung KW, Cho HW, Ju HY, Hyun JK, et al. Promising survival rate but high incidence of treatment-related mortality after reduced‐dose craniospinal radiotherapy and tandem high‐dose chemotherapy in patients with high‐risk Medulloblastoma. Cancer Med. 2020;9(16):5807–18. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/cam4.3199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS, Khasraw M. Management of glioblastoma: state of the Art and future directions. CA Cancer J Clin. 2020;70(4):299–312. https://doiorg.publicaciones.saludcastillayleon.es/10.3322/caac.21613.

    Article  PubMed  Google Scholar 

  25. Jakacki RI, Burger PC, Zhou T, Holmes EJ, Kocak M, Onar A, et al. Outcome of children with metastatic Medulloblastoma treated with carboplatin during craniospinal radiotherapy: a children’s oncology group phase I/II study. J Clin Oncol. 2012;30(21):2648–53. https://doiorg.publicaciones.saludcastillayleon.es/10.1200/JCO.2011.40.2792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lopez Guerra JL, Marrone I, Jaen J, Bruna M, Sole C, Sanchez-Reyes A, et al. Outcome and toxicity using helical tomotherapy for craniospinal irradiation in pediatric Medulloblastoma. Clin Transl Oncol. 2014;16(1):96–101. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s12094-013-1048-7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This research was funded by the State Key Laboratory of Systems Medicine for Cancer (KF2405-93), Xinhua Hospital’s National Nature Incubation Project (FH2024G099), Clinical Research Project of the Health Industry of the Shanghai Municipal Health Commission (202140119), and the Shanghai Jiao Tong University Medical & Engineering Cross Fund (YG2019QNA44).

Author information

Author notes

  1. Xuejiao Shi and Xiaoyang Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, P. R. China

    Xuejiao Shi, Xiaoyang Sun, Wenqi Fan, Xuan Dai & Mawei Jiang

Authors
  1. Xuejiao Shi
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Xiaoyang Sun
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Wenqi Fan
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Xuan Dai
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Mawei Jiang
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

JMW concepted the study; Data collection was done by FWQ and DX; Data analysis was done by SXJ and SXY; SXJ drafted the manuscript; JMW revised the manuscript; All authors were involved in data visualization.

Corresponding author

Correspondence to Mawei Jiang.

Ethics declarations

Ethical approval

This study was approved by the Ethics Committee of Xinhua Hospital (XHEC-D-2022-181).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, X., Sun, X., Fan, W. et al. Impact of radiation response on survival in pediatric medulloblastoma with residual or disseminated disease. Radiat Oncol 20, 52 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-025-02632-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-025-02632-9

Keywords

Radiation Oncology

ISSN: 1748-717X

Contact us