Abstract
Background
Effective therapy for medulloblastoma at the time of relapse is limited. The objective of this study is to review outcomes from the Seattle Children’s Hospital (SCH) institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen.
Methods
Retrospective review of patients treated for relapsed medulloblastoma from 2012-2024 treated with modified ACNS0821 therapy, including combination bevacizumab, irinotecan, and temozolomide, referred to as “TIB.” Each TIB cycle includes oral temozolomide (200 mg/m2/day) for the first 5 days, intravenous (IV) bevacizumab (10 mg/kg/dose), and IV irinotecan (125 mg/m2/dose or 340 mg/m2) on days 1 and 15 of each cycle. Patient medical history, prior treatment, therapy toxicity, response, and outcome were collected. The analysis included Kaplan–Meier estimates of 3-year overall survival (OS) and 3-year progression-free survival.
Results
Fifteen patients were treated with TIB for relapsed medulloblastoma at SCH (median age 5.81 (0.21–23.6) years, 60% male). Twelve patients completed planned therapy. Therapy was discontinued for toxicity (n = 1) and family preference (n = 1). The most common toxicities were thrombocytopenia (n = 7), neutropenia (n = 4), nausea (n = 5), vomiting (n = 5), and diarrhea (n = 3). Five patients required dose modification of one agent for toxicity. Median follow-up from TIB therapy start was 1.61 (0.47–7.66) years. Three-year OS was 48% (95% CI: 18%–74%) and 3-year event-free survival was 16% (95% CI: 1%–49%).
Conclusions
TIB was well-tolerated in pediatric patients with relapsed medulloblastoma, and outcomes were similar to those published in clinical trials. TIB therapy should be considered for patients with relapsed medulloblastoma, especially patients with limited access to care due to travel barriers.
Keywords: children, medulloblastoma, pediatric, relapse
Key Points.
A combination of temozolomide, irinotecan, and bevacizumab at this modified schedule is well-tolerated in pediatric and young adult patients with relapsed or refractory medulloblastoma.
This therapy regimen and schedule should be considered for patients with relapsed or refractory medulloblastoma, especially those with additional clinic visits that may pose an increased burden.
Importance of Study.
Effective therapy options for patients with relapsed medulloblastoma are limited. Combination chemotherapy, as published in the Children’s Oncology Group Study ACNS 0821 demonstrated improved progression-free survival with the addition of bevacizumab to irinotecan and temozolomide and is standard of care in many pediatric institutions to treat relapsed disease. This regimen involves 6 days in the clinic per each 28-day cycle, which may be burdensome to those patients who travel long distances to seek oncologic care. Here, we review outcomes from the Seattle Children’s Hospital institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen to be given over 2 days in clinic per each 28-day cycle. The data presented here demonstrate that this modified regimen appeared to be well-tolerated and the rate of progression and survival were similar to published ACNS0821 clinical trial data.
Medulloblastoma is the most common malignant central nervous system (CNS) tumor in children and young adults1 and represents approximately 20% of childhood CNS tumors. Treatment approaches for medulloblastoma are typically multimodal and include surgical resection, chemotherapy, and/or radiation therapy. The standard of care often involves a combination of these modalities tailored to the individual patient based on factors such as age, tumor subtype, and extent of disease.2,3 Typically, therapy begins with surgical resection, with the goal of maximal safe resection while preserving neurological function. In school-aged and adolescent children, craniospinal radiation therapy is administered followed by multiagent maintenance chemotherapy. In young children, a radiation-sparing approach is often utilized, which involves high-dose chemotherapy followed by autologous stem cell transplant.4–8 Specifics of treatment plans are typically adjusted for a child’s age, tumor type, and molecular features as well as extent of disease for the ultimate goal of achieving a durable cure while minimizing treatment-related complications.2,3
While current therapeutic approaches for medulloblastoma have led to a vast improvement in the efficacy of initial therapy, approximately 30% of patients experience relapse, and effective therapeutic options at the time of relapse remain limited.9–11 In the relapse setting, long-term survival remains dismal with approximately 12% surviving 5 years after relapse,10 emphasizing the importance of optimizing care in this at-risk population.
The Children’s Oncology Group (COG) completed a randomized phase 2 trial (ACNS0821, NCT01217437) evaluating combination chemotherapy in 28-day cycles with temozolomide, and irinotecan for days 1–5 versus temozolomide, irinotecan with bevacizumab on days 1 and 15 of each cycle in children and young adults with relapsed medulloblastoma. In this trial, bevacizumab-containing combination chemotherapy was found to be superior compared with temozolomide and irinotecan alone and both arms improved survival when compared to previously reported regimens for relapsed medulloblastoma.9 Specifically, median overall survival on the ACNS0821 trial was 19 months in the arm containing bevacizumab compared to 13 months with temozolomide and irinotecan alone.9 Following the publication of these results, many centers adopted this regimen as standard therapy for patients with relapsed medulloblastoma to prolong survival.
The ACNS0821 regimen involves daily intravenous chemotherapy for the first 5 days and day 15 of a total 28-day cycle, thereby necessitating multiple visits to an ambulatory clinic or infusion center each cycle. Concurrently, during the development of the ACNS0821 trial, a cohort of 9 patients with medulloblastoma were described, and treated with the same regimen; however, with a modified dosing regimen of visits every 2 weeks.12
Seattle Children’s Hospital is a stand-alone tertiary care children’s hospital in the Pacific Northwest of the United States with the largest regional pediatric neuro-oncology tumor program and serves a wide geographical area that includes Washington State, Alaska, Montana, and Idaho. Due to the institutional geographic reach, patients and families travel great distances to receive oncologic care and, as such, the neuro-oncology program has modified regimens to optimize therapeutic effect while maintaining safety and minimizing travel burden for families. Furthermore, recent reports have demonstrated decreased therapy compliance and worsened patient quality-of-life for those oncology patients who are required to travel long distances for care.13–16 In an effort to reduce this travel burden for patients, our local institution’s neuro-oncology tumor team modified the ACNS0821 regimen for patients with relapsed medulloblastoma. Here, we review our institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen.
Methods
Patients and Study Procedures
This study was approved by the Seattle Children’s Institutional Review Board (STUDY00000945). We retrospectively reviewed patients with relapsed medulloblastoma from 2012-2024 who were treated with modified ACNS0821 therapy, including a combination of bevacizumab, irinotecan, and temozolomide, referred to as “TIB.” Electronic records were reviewed retrospectively and patient demographics, diagnosis, disease staging, upfront therapy and response, relapse location and staging, relapse therapy and response, complications, and outcome were collected.
Treatment Regimen
The Seattle Children’s relapsed medulloblastoma standard therapy (“TIB”) was adapted from the Children’s Oncology Group Protocol, ACNS0821, and includes 28-day cycles. Each cycle includes oral temozolomide (200 mg/m2/day) for the first 5 days, and intravenous (IV) bevacizumab (10 mg/kg/dose) and IV irinotecan (125 mg/m2/dose) on days 1 and 15 of each cycle (Supplementary Figure 1). TIB was offered as one of multiple treatment options available at the time of relapsed/progressive disease and planned for 12 cycles or until no longer tolerable or beneficial for the patient.
TIB was administered in an ambulatory setting. Supportive care measures included pre-medications with ondansetron and diphenhydramine for nausea and to prevent infusion reactions, respectively. Atropine and loperamide guidelines were provided for the management of irinotecan-induced diarrhea as needed for infusion or for late diarrheal symptoms, respectively. All patients were also treated with oral trimethoprim-sulfamethoxazole (5 mg TMP/kg/day) for 2 days/week for prevention of pneumocystis jiroveci pneumonia.
Response and Safety
MRI of the brain and spine with gadolinium contrast was performed prior to TIB therapy start and at 3-month intervals or earlier if clinical concerns. Radiographic interpretation was reviewed retrospectively and is reported according to a modified RANO criteria.17 Complete response (CR) was defined as the disappearance of all enhancing disease (measurable and non-measurable), partial response (PR) was defined as 50% or more decrease of all measurable enhancing lesions, progression was defined as 25% or more increase in size of lesion, stable disease (SD) was defined as does not qualify for CR, PR or progression. Patient data were reviewed via secure electronic medical record and all adverse events during TIB therapy were collected, as well as all reasons for dose modification.
Analysis
All variables were summarized descriptively. Overall survival (OS) was defined as the time from the date of TIB therapy start to the date of death from any cause or last follow-up. Event-free survival (EFS) was defined as the time from the date of TIB therapy start to the date of subsequent relapse, progression, death, or last follow-up. We used Kaplan–Meier methods to estimate 3-year and 5-year OS and EFS and plot survival curves for both outcomes. Statistical analyses were performed using STATA software version 18 (College Station, Texas).
Results
Fifteen patients with a histologic or integrated histologic and molecular diagnosis of medulloblastoma were treated with a combination of temozolomide, irinotecan, and bevacizumab after upfront therapy. Patient demographics are shown in Table 1.
Table 1.
Patient Demographics
| N = 15 N (%) | |
|---|---|
| Age at diagnosis (years) | 5.81 (0.21–23.6) |
| % male | 9 (60.0) |
| Group | |
| WNT | 1 (6.7) |
| SHH | 1 (6.7) |
| Group 3 | 2 (13.3) |
| Group 4 | 2 (13.3) |
| Non-SHH/non-WNT (group 3 or 4) | 9 (60.0) |
| Metastatic disease at initial diagnosis | 5 (33.3) |
| Initial surgery—primary lesion | |
| GTR | 9 (60.0) |
| STR | 5 (33.3) |
| Biopsy | 1 (6.7) |
| Initial chemotherapy protocol | |
| CCG9961 Reg A | 6 (40.0) |
| ACNS0332 Reg A | 3 (20.0) |
| ACNS0334 Reg A | 2 (13.3) |
| ACNS0334 Reg B | 4 (26.7) |
| Initial radiation N (%) | 9 (60.0) |
| CSI dose 23.4 Gy | 5 (33.3) |
| CSI dose 36 Gy | 4 (26.7) |
| Relapse surgery | |
| GTR | 1 (6.7) |
| STR | 2 (13.3) |
| Biopsy | 2 (13.3) |
| Relapse radiation N (%) | 7 (46.7) |
| Focal | 4 (26.7) |
| CSI | 3 (20.0) |
CSI, craniospinal radiation; GTR, gross total resection; STR, subtotal resection.
Molecular Information
Medulloblastoma grouping practice has evolved over the time period that this cohort was treated and in its current state is consistently completed in all patients. Within this cohort, medulloblastoma grouping was completed using a methylation array and targeted next-generation sequencing (NGS) either at diagnosis or time of relapse in 7 patients. The group included WNT (n = 1), SHH (n = 2), group 3 (n = 2), and group 4 (n = 1). In the 9 patients where the medulloblastoma subgroup was unknown, 6 tumors were non-SHH/non-WNT by NGS and 2 did not have molecular information available. Molecular sequencing revealed a somatic TP53 mutation in 2 patients and a somatic SMARCA4 alteration in one patient. In 1 patient, the histology of the tumor was initially classified as medulloblastoma but was subsequently re-classified using molecular information as having a RELA fusion and therefore most likely in keeping with an embryonal tumor not otherwise specified. That patient was not included in the Kaplan–Meier analyses.
Upfront Therapy
Therapy for each patient is summarized in Table 2. Upfront therapy prior to bevacizumab, irinotecan, and temozolomide included craniospinal radiation (CSI) with maintenance chemotherapy (n = 9) or high-dose chemotherapy with autologous stem cell rescue (n = 6).
Table 2.
Treatment Description
| Subject | Sex | Age (initial dx) | Initial staging* | Group | Initial RT | Previous chemotherapy regimen | Time to relapse (years) and relapse site | Relapse radiation | Abbreviated TIB | Number of cycles | TIB to follow-up (years) |
Current status | Subsequent Rx |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 2.5 | M0 | Group 3 | None | ACNS0334 Reg B | 1.04 Spine, CSF |
None | Standard, with IT MTX x 2 cycles | 12 | 0.97 | AWD | RT |
| 2 | M | 5.8 | M2 | Group 4 | None | ACNS 0334 Reg B | 1.89 Leptomeningeal |
Proton, CSI 36 Gy, PFB 54 Gy, thecal sac bst 50.4 Gy | Standard | 4 | 0.47# | AWD | TIB ongoing |
| 3 | M | 13.8 | M0 | Group 4 | Proton CSI 23.4 Gy, PFB 54 Gy | CCG 9961 Reg A | 5.39 Spine |
Proton, CSI 23.4 Gy; Spine bst 50.4 Gy | Standard | 6 | 0.92 | NED | None |
| 4 | M | 5.8 | M0 | Group 3/4 | Proton CSI 23.4 Gy; PFB 54 Gy | CCG 9962 Reg A | 2.50 Spine |
None | Standard, followed by 4 cycles BI | 16 | 3.81 | AWD | IT MTX, oral etoposide, IT topotecan |
| 5 | F | 12.9 | M0 | WNT | Proton CSI 23.4 Gy, PFB 54 Gy | CCG9961 Reg A | 2.85 Brain |
Photon, focal PF 50.4 Gy | Standard | 2 | 0.65 | DOC | None |
| 6 | M | 22.6 | M3 | Group 3 | Photon CSI 36 Gy, PFB 55.8 Gy | ACNS0332 Reg A | 1.68 Brain |
Photon, focal, 25 Gy | Standard | 12 | 2.89 | DOD | RT |
| 7 | F | 0.21 | M0 | RELA Fusion ET | None | ACNS 0334B | 3.29 Multiple lesions, brain |
Proton, CSI 36 Gy, PFB 54 Gy | Standard | 12 | 3.99 | AWD | Oral etoposide |
| 8 | M | 2.8 | M2 | Group 3/4 | None | ACNS 0334 Reg B | N/A N/A, persistent disease |
None | Standard | 6 | 3.34 | NED | None |
| 9 | M | 23.6 | M0 | SHH | Photon CSI 36 Gy, PFB 54 Gy | CCG9961 Reg A | 3.22 Brain |
Gamma knife | Standard, 2 doses B omitted | 12 | 2.11 | NED | Vismodegib |
| 10 | F | 1.5 | M0 | Group 3/4 | None | ACNS0334 Reg A | 1.43 Leptomeningeal |
None | Standard | 12 | 2.27 | NED | None |
| 11 | F | 11.8 | M0 | Group 3/4 | CSI 23.4 Gy, PFB 54 Gy | CCG9961 Reg A | 1.37 Brain and spine |
None | Standard | 12 | 0.69 | DOD | IT MTX, Gamma knife |
| 12 | M | 7.7 | M3 | Group 3/4 | CSI 36 Gy | ACNS0332 Reg A | 1.83 Brain and spine |
Focal photon, 35 Gy | Standard, B omitted cycles 7-12 | 12 | 7.66 | AWD | Laser ablation, Phase 1 trials, focal RT 25 Gy |
| 13 | M | 11.8 | M2 | Group 3/4 | CSI 36 Gy | ACNS0332 Reg A | 1.12 Brain and spine |
None | Standard | 12 | 0.47 | DOD | None |
| 14 | M | 1.3 | M0 | Group 3/4 | CSI 23.4 Gy | CCG9961 Reg A | 1.61 Brain and spine |
None | Standard | 12 | 1.61 | DOD | None |
| 15 | F | 2.8 | M0 | Group 3/4 | None | ACNS0334 Reg A | 1.34 Leptomeningeal |
None | Standard | 8 | 1.11 | DOD | IT MTX |
AWD, alive with disease; B, bevacizumab; BI, bevacizumab and irinotecan; bst, boost: CSI, craniospinal radiation; DOC, died of other cause; DOD, died of disease; Dx, diagnosis; ET, embryonal tumor; Fx, fraction; IT, intrathecal; MTX, methotrexate; NED, no evidence of disease; N/A, not applicable; PFB, posterior fossa boost; RT, radiation therapy; Rx, treatment.
*Chang staging [Dufour C, et al. Metastatic Medulloblastoma in Childhood: Chang’s Classification Revisited. Int J Surg Oncol. 2012;2012:245385. PMID: 22312539].
#TIB Therapy ongoing.
Abbreviated TIB (Standard): 28-day cycles including oral temozolomide (200 mg/m2/day) for the first 5 days, intravenous (IV) bevacizumab (10 mg/kg/dose) every 2 weeks, and IV irinotecan (125 mg/m2/dose or 340 mg/m2 depending on status of anticonvulsant therapy) every 2 weeks.
Therapy at Recurrence
Twelve of the fifteen patients (80%) had metastatic disease at relapse. Seven patients underwent radiation at relapse followed by TIB therapy (focal n = 4, CSI n = 3). Two patients received craniospinal radiation to 36 Gy and 1 received 23 Gy. Focal radiation dose was 25–54 Gy. Three patients received TIB without any prior radiation therapy. Two patients received intrathecal methotrexate during TIB therapy, and 3 additional patients received intrathecal methotrexate after completion of TIB at a subsequent relapse. Ten patients had subsequent disease relapse or progression following TIB therapy. Other therapies beyond radiation and TIB included oral etoposide (n = 3) and vismodegib (n = 1). Two patients enrolled in an early phase clinical trial (one prior to TIB therapy and one following TIB therapy at the time of the second progression).
Therapy Tolerance
Median number of cycles received was 12 (range 4–16). Therapy was discontinued for toxicity in 1 patient, family preference in 1 patient, and completion of planned 12 cycles in 10 patients and 6 cycles in 2 patients. Therapy is ongoing in one patient.
Toxicities are shown in Table 3. The most common toxicity experienced during TIB therapy was thrombocytopenia (n = 7, 46.7%). Neutropenia (n = 4, 26.7%), nausea (n = 5, 33.3%), vomiting (n = 5, 33.3%), and diarrhea (n = 3, 20%) were also seen within this cohort. One patient required loperamide for diarrhea during one cycle. Transfusion of red blood cells was required in 2 patients (13%) and transfusion of platelets was required in 3 patients (20%). Granulocyte colony-stimulating factor (G-CSF) was not administered to any patients. One patient discontinued irinotecan due to an infusion reaction (flushing, hypotension); however, continued with a combination of temozolomide and bevacizumab. One patient received a decreased temozolomide dose for 2 cycles and 2 patients received a decreased temozolomide dose for 1 cycle due to cytopenias. Two patients missed 1 dose (n = 1) and 2 doses (n = 1) of bevacizumab due to concurrent surgery for central line placement. Two patients missed bevacizumab for 2 doses (n = 1) and 6 cycles (n = 1) due to hypertension and proteinuria. Two patients had admissions during TIB therapy, one for viral illness leading to respiratory distress and one for fever in the setting of neutropenia.
Table 3.
Toxicity During TIB
| Adverse events during therapy N (%) |
Toxicity-related TIB modification N |
|
|---|---|---|
| Thrombocytopenia | 7 (46.7) | 1 (temozolomide and irinotecan) |
| Anemia | 3 (20.0) | 0 |
| Neutropenia | 4 (26.7) | 1 (temozolomide and irinotecan) |
| Wound healing | 2 (13.3) | 1 (bevacizumab) |
| Nausea/vomiting | 5 (33.3) | 1 (temozolomide) |
| Diarrhea | 3 (20.0) | 0 |
| Infection | 2 (13.3) | 0 |
| Hypertension with proteinuria | 2 (13.3) | 1 |
| Hypotension | 1 (6.7) | 1 (irinotecan) |
TIB, temozolomide, irinotecan, bevacizumab.
Outcomes
Imaging follow-up during TIB demonstrated CR (n = 2), PR (n = 6), SD (n = 4), and progressive disease (n = 3). Notably, one patient with a CR had refractory leptomeningeal (LM) disease (rather than relapse) after high-dose chemotherapy and autologous stem cell transplant and had not received radiation therapy. One patient had ongoing evidence of response to TIB therapy after 12 cycles and thus completed an additional 4 cycles of therapy, following which there was no evidence of disease. Median follow-up from TIB therapy start was 1.61 (range:0.47–7.66) years. Event-free survival and overall survival are shown in Figure 1A and B, respectively. Three-year overall survival was 48% [95% CI: 18%–74%]. Three-year EFS was 16% [95% CI: 1%–49%].
Figure 1.
(A) Event-free survival. (B) Overall survival.
Eight patients subsequently had a second progression after TIB therapy. Currently, within this cohort, there are 6 patients who have died due to tumor progression and 9 patients who were alive at the time of the last follow-up.
Discussion
Here we demonstrate the feasibility and tolerability of a modified TIB chemotherapy schedule in a single center, in a pediatric and young adult patient population with relapsed medulloblastoma.
The modified TIB regimen as described in this manuscript includes outpatient-administered chemotherapy for 2 days out of a 28-day cycle, rather than 6 days required on the ACNS0821 trial.9 This reduction in clinic days was designed to allow patients to travel to our institution twice per cycle with the goal to reduce extended periods of time away from home. The only difference was on the dosing schedule for irinotecan, whereas within the ACNS0821 trial, irinotecan is given intravenously for 5 days at the start of the cycle; however, here we delivered it on days 1 and 15 of each cycle in conjunction with bevacizumab. The total irinotecan dose per cycle (250 mg/m2) is identical between the 2 regimens.
This retrospective cohort demonstrates the well-established survival benefit of a combination of temozolomide, irinotecan, and bevacizumab for children and young adults with relapsed medulloblastoma. Of note, 7 patients within this cohort received radiation therapy and 3 received intrathecal methotrexate at the time of relapse in addition to TIB therapy. We did not observe a decrease in response or survival when compared to pediatric patients with medulloblastoma treated with the same 3 agents in the COG ACNS0821 trial.9 The 3-year OS of 48% (95% CI: 0.18–0.74) and 3-year progression-free survival (PFS) of 16% (95% CI: 0.01–0.49) seen in this cohort of patients were not decreased when compared to the estimated 3-year OS (25%) and 3-year PFS (20%) seen within the COG ACNS0821 trial arm containing the same 3 agents.9 While not powered to match/adjust and therefore detect significant differences between these 2 studies, it is reassuring that this modification in therapy schedule does not seem to be associated with a worsening in response or overall survival.
Overall, the TIB regimen was tolerated within this group of pediatric and young adult patients with relapsed medulloblastoma. Most relapse regimens for medulloblastoma involving multiagent chemotherapy are associated with significant toxicity, typically exacerbated by this fragile, often heavily pretreated patient population.2,9,10 Importantly, there was only 1 patient within this cohort who discontinued therapy due to therapy-related toxicity. Two-thirds of patients completed all planned cycles, a higher proportion than was seen within patients with medulloblastoma receiving TIB therapy on ACNS0821 (25%). Reported toxicity within this cohort was similar to that seen in the prior trial, with the most common toxicity being cytopenias and nausea/vomiting. Notably, the diarrhea incidence in this cohort was similar to that seen in prior publications; however, in this current cohort, few patients required loperamide supportive care. Therapy doses were missed in one-third of patients within this cohort, compared to close to half of patients treated on the ACNS0821 trial TIB arm. Within another retrospective cohort of 9 pediatric patients with relapsed medulloblastoma treated with a combination of temozolomide, irinotecan, and bevacizumab, toxicity was also similar to that observed within the current cohort, and the most common toxicity were cytopenias and diarrhea.12
It is well documented that increased travel and time away from home negatively impact cancer patients’ care and quality of life13 and our institutional TIB regimen is one example of therapy modification that may mitigate this burden for patients. Importantly, this cohort treated on our institutionally modified schedule does not demonstrate a clear difference in either response/survival or toxicity when compared to the larger cohort treated within the clinical trial.
Strengths and Limitations
These data must be interpreted within their limitations. Notably, this is a retrospective review of a cohort of pediatric patients with relapsed medulloblastoma previously treated with this regimen. As such, data were limited to that available within the patient record. Also, we were not powered to analyze therapy response by the medulloblastoma group as has been recommended in current trials18 due to this small sample size. Also, some patients within this cohort received radiation therapy or intrathecal therapy at the time of relapse, which is discordant with the therapy permitted in the published clinical trial. Furthermore, subsequent therapy for second relapse varied within this patient population and the small numbers within this cohort limited further analysis of follow-up therapy and its impact on survival. Nevertheless, this cohort represents a group of patients treated by a single team at a single institution, and therefore both tumor-directed therapy and supportive care measures were consistent amongst these patients. Although limited by the factors above, in descriptive review, survival within this cohort is comparable with published clinical trials, which provides reassurance of the potential use of this modified TIB schedule in a variety of clinical settings. Finally, while it is well documented that quality of life is impacted by travel to medical appointments, we did not directly measure or collect specific data on quality of life and were not able to discern the impact of the reduction in travel for this cohort, as this data was collected retrospectively. This is something that should be evaluated in a prospective cohort.
Conclusions
TIB therapy was well-tolerated in pediatric patients with relapsed medulloblastoma treated within this single institution. Overall survival was increased when compared to many pediatric medulloblastoma therapeutic approaches and not decreased when compared to the COG ACNS0821 trial utilizing the same drug combination. TIB therapy administered on this schedule should be considered for pediatric and young adult patients with relapsed medulloblastoma, especially those who may benefit from a decrease in clinic and hospital travel.
Supplementary material
Supplementary material is available online at Neuro-Oncology Practice (https://academic.oup.com/nop/).
Acknowledgments
None.
Contributor Information
Rebecca Ronsley, Fred Hutch Cancer Center, Seattle, Washington, USA; Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, Washington, USA; Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Miranda C Bradford, Biostatistics Epidemiology and Analytics in Research (BEAR) Core, Seattle Children’s Research Institute, Seattle, Washington, USA.
Erin E Crotty, Fred Hutch Cancer Center, Seattle, Washington, USA; Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, Washington, USA; Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Nicholas A Vitanza, Fred Hutch Cancer Center, Seattle, Washington, USA; Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, Washington, USA; Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Daniel V Runco, Fred Hutch Cancer Center, Seattle, Washington, USA; Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, Washington, USA; Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Jeffrey Stevens, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Corinne Hoeppner, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Susan L Holtzclaw, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Amy R Wein, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Amy Lee, Division of Neurosurgery, Seattle Children’s Hospital and Department of Neurological Surgery, University of Washington, Seattle, Washington, USA.
Bonnie L Cole, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Ralph Ermoian, Department of Radiation Oncology, University of Washington, Seattle, Washington, USA.
Sarah E S Leary, Fred Hutch Cancer Center, Seattle, Washington, USA; Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, Washington, USA; Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA.
Funding
This work was unfunded.
Conflict of interest statement
The authors have no relevant conflicts of interest or disclosures related to this manuscript.
Authorship statement
Design: R.R. and S.E.S.L.; Data collection: R.R. and J.S.; Data analysis: R.R. and M.C.B., Manuscript initial draft: R.R., M.C.B., and S.E.S.L.; Clinical care of patients: R.R., E.E.C., N.A.V., D.V.R., S.L.H., C.H., A.R.W., A.L., R.E., and S.E.S.L.; Manuscript critical review: all authors.
Data availability
Raw data are available upon request.
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Data Availability Statement
Raw data are available upon request.