Re-irradiation for children with recurrent medulloblastoma in Toronto, Canada: a 20-year experience

Tsang, Derek S.; Sarhan, Nasim; Ramaswamy, Vijay; Nobre, Liana; Yee, Ryan; Taylor, Michael D.; Hawkins, Cynthia; Bartels, Ute; Huang, Annie; Tabori, Uri; Hodgson, David C.; Bouffet, Éric; Laperrière, Normand

doi:10.1007/s11060-019-03272-2

Cited by 21 publications

(27 citation statements)

References 21 publications

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“…(12). Although Tsang et al were unable to evaluate the role of repeat CSI, the very high incidence of distant failures amongst their 14 patients treated with focal re-irradiation, suggested that CSI may be one of the treatment tools of distant disease control (13). Our study showed an OS advantage of re-irradiation as part of a multiagent approach over the history reports, with signi cantly better outcome in the CSI subgroup.…”

Section: Discussionmentioning

confidence: 51%

“…Previously, the study from St. Jude Children's Research Hospital suggested that undergoing a second course of radiation may have contributed to better overall survival in patients with recurrent medulloblastoma and may be considered a reasonable salvage treatment option in selected patients who have minimal residual disease at the time of recurrence (12). Furthermore, Sick Children Hospital experience showed that re-irradiation can offer some patients disease control, particularly those with focally recurrent disease in the brain but poor outcome in symptomatic recurrence or disseminated disease (13). Recently, Gupta et al provided encouraging survival outcomes with acceptable toxicity in selected recurrent medulloblastoma treated by reirradiation as part of multimodality salvage therapy (14).…”

Section: Introductionmentioning

confidence: 99%

“…Craniospinal irradiation (CSI) as a component of re-irradiation was previously reported in small series (12,13,14). Recently, the Sick Children group suggested that CSI could be considered one of the treatment tools to help with distant tumor control, considering the very high incidence of distant failures after focal reirradiation (13). Moreover, Gupta et al suggested that recurrence medulloblastoma with leptomeningeal dissemination could be bene ted by re-CSI (14).…”

Section: Introductionmentioning

confidence: 99%

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Craniospinal irradiation as part of re-irradiation for children with recurrent medulloblastoma

et al. 2021

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BackgroundMany studies have demonstrated in the last years that once medulloblastoma has recurred, the probability of regaining tumor control is poor despite salvage therapy. Although re-irradiation has an emerging role in other relapsed brain tumors, there is a lack of strong data on re-irradiation for medulloblastoma. MethodsThis is a retrospective cohort study of patients aged 18 years or under, treated at least by a second course of external beam for recurrence medulloblastoma at Garrahan Hospital between 2009 and 2020. Twenty-four patients met eligibility criteria for inclusion. All patients received upfront radiotherapy as part of the curative-intent rst radiotherapy, either craniospinal irradiation (CSI) followed by posterior fossa boost in 20 patients or focal posterior fossa radiation in 4 infants. The second course of radiation consisted of CSI in 15 and focal in 9. The 3-year post rst failure OS (50% vs. 0%; p = 0.0010) was signi cantly better for children who received re-CSI compared to children who received focal re-irradiation. Similarly, the 3-year post-re-RT PFS (31% vs. 0%; p = 0.0005) and OS (25% vs. 0%; p = 0.0003) was signi cantly improved for patients who received re-CSI compared to patients who received focal re-irradiation. No symptomatic intratumoral haemorrhagic events or symptomatic radionecrosis were observed. Survivors fell within mild to moderate intellectual disability range, with a median IQ at last assessment of 58 (range 43-69). ConclusionRe-irradiation with CSI is a safe and effective treatment for children with relapsed medulloblastoma; improves disease control and survival compared with focal re-irradiation. However this approach carries a high neurocognitive cost.All radiation treatments were given at Garrahan Hospital, Buenos Aires, Argentina. Photon external beam therapy was used for all patients. All but four patients received CSI as part of the rst radiation course (RT1), followed by a boost to the entire posterior fossa. Standard risk (SR) patients received CSI 23.4Gy followed by posterior fossa boost 30.6Gy and high-risk (HR) patients received CSI 36Gy followed by posterior fossa boost 19.8Gy. Except for one, all of them received maintenance platinum based chemotherapy; SR as per ACNS0331 (N=2) and COG 9961 (regimen A=3, regimen B= 6); HR as per ACNS0332 (Regimen A=4, Regimen B=4). Four patients received upfront posterior fossa radiotherapy (54 Gy) due to the young age at diagnosis as per standard of care treatment administered between 2002 and 2020 at Hospital Garrahan, based on a modi ed POG-9934 strategy (15). Upon recurrence, most patients with brain solitary lesions were offered surgery followed by metronomic chemotherapy and a second course of irradiation (RT2), while those with multifocal disease received chemotherapy followed by radiotherapy. CSI was administered using standard beam's eye-view treatment planning techniques. Boost treatment and focal radiotherapy was administered using 3D-conformal radiation therapy methods. Hypofractionated stereotactic radiother...

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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Craniospinal irradiation as part of re-irradiation for children with recurrent medulloblastoma

et al. 2021

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“…In addition, the development of more precise irradiation techniques alongside smaller target volumes may allow safer re-irradiation while minimising the dose to surrounding critical structures [ 87 ]. There is now a growing number of studies reporting feasibility and low rates of second malignancies and radionecrosis after re-irradiation for rMB [ 72 , 84 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ]. However, while both focal and CSI re-irradiation are increasingly considered as part of salvage therapy for rMB, only a minority of studies offer clear evidence for improved survival, which is highly dependent on principal molecular group and the re-irradiated site [ 72 , 84 , 88 , 93 ].…”

Section: Treatment Modalities and Considerationsmentioning

confidence: 99%

Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment

Hill

Plasschaert

Timmermann

et al. 2021

Cancers

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Relapsed medulloblastoma (rMB) accounts for a considerable, and disproportionate amount of childhood cancer deaths. Recent advances have gone someway to characterising disease biology at relapse including second malignancies that often cannot be distinguished from relapse on imaging alone. Furthermore, there are now multiple international early-phase trials exploring drug–target matches across a range of high-risk/relapsed paediatric tumours. Despite these advances, treatment at relapse in pre-irradiated patients is typically non-curative and focuses on providing life-prolonging and symptom-modifying care that is tailored to the needs and wishes of the individual and their family. Here, we describe the current understanding of prognostic factors at disease relapse such as principal molecular group, adverse molecular biology, and timing of relapse. We provide an overview of the clinical diagnostic process including signs and symptoms, staging investigations, and molecular pathology, followed by a summary of treatment modalities and considerations. Finally, we summarise future directions to progress understanding of treatment resistance and the biological mechanisms underpinning early therapy-refractory and relapsed disease. These initiatives include development of comprehensive and collaborative molecular profiling approaches at relapse, liquid biopsies such as cerebrospinal fluid (CSF) as a biomarker of minimal residual disease (MRD), modelling strategies, and the use of primary tumour material for real-time drug screening approaches.

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“…Patients with relapsed medulloblastoma have dismal outcomes, with a 3-year survival rate after relapse of less than 25% [39]. The treatment of relapsed and refractory medulloblastoma is varied, and options include re-irradiation [40], additional cytotoxic chemotherapy [41], and targeted agents [42]. There are greater than 20 currently open clinical trials that are enrolling children with relapsed medulloblastoma.…”

Section: Relapsed Medulloblastoma Treatmentmentioning

confidence: 99%

Overview and recent advances in the targeting of medulloblastoma cancer stem cells

Paul

Zage

2021

Expert Review of Anticancer Therapy

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Introduction: Medulloblastoma, an embryonal small round blue cell tumor primarily arising in the posterior fossa, is the most common malignancy of the central nervous system in children and requires intensive multi-modality therapy for cure. Overall 5-year survival is approximately 75% in children with primary disease, but outcomes for relapsed disease are very poor. Recent advances have identified molecular subgroups with excellent prognosis, with 5-year overall survival rates >90%, and subgroups with very poor prognosis with overall survival rates <50%. Molecular subtyping has allowed for more sophisticated risk stratification of patients, but new treatments for the highest risk patients have not yet improved outcomes. Targeting cancer stem cells may improve outcomes, and several candidate targets and novel drugs are under investigation. Areas covered: We discuss medulloblastoma epidemiology, biology, treatment modalities, risk stratification, and molecular subgroup analysis, links between subgroup and developmental biology, cancer stem cell biology in medulloblastoma including previously described cancer stem cell markers and proposed targeted treatments in the current literature. Expert opinion: The understanding of cancer stem cells in medulloblastoma will advance therapies targeting the most treatment-resistant cells within the tumor and therefore reduce the incidence of treatment refractory and relapsed disease.

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Re-irradiation for children with recurrent medulloblastoma in Toronto, Canada: a 20-year experience

Cited by 21 publications

References 21 publications

Craniospinal irradiation as part of re-irradiation for children with recurrent medulloblastoma

Craniospinal irradiation as part of re-irradiation for children with recurrent medulloblastoma

Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment

Overview and recent advances in the targeting of medulloblastoma cancer stem cells

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