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

Abstract

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...

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

“…However, small patient numbers, heterogeneous treatment approaches and an understandable tendency to restrict care to palliative options preclude a clear understanding of the impact of surgery in rMB. Indeed, many reports have either not investigated, or not demonstrated the benefit of surgery at relapse [ 3 , 5 , 8 , 21 , 72 ].…”

“…Re-irradiation offers the potential to decelerate tumour progression, reduce symptoms, and in some cases, provide long-term disease control [ 72 , 84 ]. Re-irradiation of the CNS is associated with the risk of cumulative toxicity, including brain necrosis.…”

“…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 ].…”

“…As a rule, it is feasible to accept up to a total cumulative dose of 100 Gy to limited areas of the brain for conventional radiation techniques and up to 135 Gy with high-precision techniques such as stereotactic radiotherapy (SRT) and radiosurgery (SRS) [ 93 , 94 , 95 , 96 ]. Typically, a time interval of 6 months between first and second radiotherapy is acceptable and tolerated [ 72 , 97 ].…”

“…Given the reduction in initial CSI dose for low- and standard-risk MB (18–24 Gy), re-irradiation with second CSI may also be feasible albeit with unclear or mixed reports of additional benefit when compared to delivery of focal radiotherapy at relapse [ 72 , 94 ]. Most recently, Baroni et al reported on 12 patients in receipt of second CSI.…”