Abstract：
We characterize the patterns of progression across medulloblastoma (MB) clinical risk and molecular subgroups from SJMB03, a Phase III clinical trial.
One hundred and fifty-five pediatric patients with newly diagnosed MB were treated on a prospective, multi-center phase III trial of adjuvant radiotherapy (RT) and dose-intense chemotherapy with autologous stem cell transplant. Craniospinal radiotherapy to 23.4 Gy (average risk, AR) or 36-39.6 Gy (high risk, HR) was followed by conformal RT with a 1 cm clinical target volume to a cumulative dose of 55.8 Gy. Subgroup was determined using 450K DNA methylation. Progression was classified anatomically (primary site failure (PSF) +/- distant failure (DF), or isolated DF), and dosimetrically.
Thirty-two patients have progressed (median follow-up 11.0 years (range, 0.3-16.5 y) for patients without progression). Anatomic failure pattern differed by clinical risk (P = .0054) and methylation subgroup (P = .0034). The 5-year cumulative incidence (CI) of PSF was 5.1% and 5.6% in AR and HR patients, respectively (P = .92), and did not differ across subgroups (P = .15). 5-year CI of DF was 7.1% vs. 28.1% for AR vs. HR (P = .0003); and 0% for WNT, 15.3% for SHH, 32.9% for G3, and 9.7% for G4 (P = .0024). Of 9 patients with PSF, 8 were within the primary site RT field and 4 represented SHH tumors.
The low incidence of PSF following conformal primary site RT is comparable to prior studies using larger primary site or posterior fossa boost volumes. Distinct anatomic failure patterns across MB subgroups suggest subgroup-specific treatment strategies should be considered.
One hundred and fifty-five pediatric patients with newly diagnosed MB were treated on a prospective, multi-center phase III trial of adjuvant radiotherapy (RT) and dose-intense chemotherapy with autologous stem cell transplant. Craniospinal radiotherapy to 23.4 Gy (average risk, AR) or 36-39.6 Gy (high risk, HR) was followed by conformal RT with a 1 cm clinical target volume to a cumulative dose of 55.8 Gy. Subgroup was determined using 450K DNA methylation. Progression was classified anatomically (primary site failure (PSF) +/- distant failure (DF), or isolated DF), and dosimetrically.
Thirty-two patients have progressed (median follow-up 11.0 years (range, 0.3-16.5 y) for patients without progression). Anatomic failure pattern differed by clinical risk (P = .0054) and methylation subgroup (P = .0034). The 5-year cumulative incidence (CI) of PSF was 5.1% and 5.6% in AR and HR patients, respectively (P = .92), and did not differ across subgroups (P = .15). 5-year CI of DF was 7.1% vs. 28.1% for AR vs. HR (P = .0003); and 0% for WNT, 15.3% for SHH, 32.9% for G3, and 9.7% for G4 (P = .0024). Of 9 patients with PSF, 8 were within the primary site RT field and 4 represented SHH tumors.
The low incidence of PSF following conformal primary site RT is comparable to prior studies using larger primary site or posterior fossa boost volumes. Distinct anatomic failure patterns across MB subgroups suggest subgroup-specific treatment strategies should be considered.
摘要：
我们从III期临床试验SJMB03中表征了髓母细胞瘤（MB）临床风险和分子亚群的进展模式。
有前瞻性地治疗了125例新诊断为MB的儿科患者，辅助放疗（RT）和剂量强烈化疗联合自体干细胞移植的多中心III期试验。头颅脊柱放疗至23.4Gy（平均风险，AR）或36-39.6Gy（高风险，HR）之后是适形RT，临床目标体积为1cm，累积剂量为55.8Gy。使用450KDNA甲基化确定亚组。进展按解剖学分类(原发部位衰竭(PSF)+/-远处衰竭(DF),或隔离DF)，和剂量学。
32例患者进展（中位随访11.0年（范围，0.3-16.5y），适用于无进展的患者）。解剖失败模式因临床风险（P=.0054）和甲基化亚组（P=.0034）而异。在AR和HR患者中，PSF的5年累积发生率（CI）分别为5.1％和5.6％，分别为（P=0.92），并且在各个亚组之间没有差异（P=0.15）。DF的5年CI为7.1%，而不是AR与AR的28.1%HR（P=.0003）；WNT为0%，SHH为15.3%，G3为32.9%，G4为9.7%（P=.0024）。在9例PSF患者中，8个在原发部位RT区域内,4个代表SHH肿瘤。
适形原发部位RT后PSF的低发生率与使用较大原发部位或后颅窝增大体积的先前研究相当。MB亚组不同的解剖失败模式表明，应考虑亚组特异性治疗策略。
有前瞻性地治疗了125例新诊断为MB的儿科患者，辅助放疗（RT）和剂量强烈化疗联合自体干细胞移植的多中心III期试验。头颅脊柱放疗至23.4Gy（平均风险，AR）或36-39.6Gy（高风险，HR）之后是适形RT，临床目标体积为1cm，累积剂量为55.8Gy。使用450KDNA甲基化确定亚组。进展按解剖学分类(原发部位衰竭(PSF)+/-远处衰竭(DF),或隔离DF)，和剂量学。
32例患者进展（中位随访11.0年（范围，0.3-16.5y），适用于无进展的患者）。解剖失败模式因临床风险（P=.0054）和甲基化亚组（P=.0034）而异。在AR和HR患者中，PSF的5年累积发生率（CI）分别为5.1％和5.6％，分别为（P=0.92），并且在各个亚组之间没有差异（P=0.15）。DF的5年CI为7.1%，而不是AR与AR的28.1%HR（P=.0003）；WNT为0%，SHH为15.3%，G3为32.9%，G4为9.7%（P=.0024）。在9例PSF患者中，8个在原发部位RT区域内,4个代表SHH肿瘤。
适形原发部位RT后PSF的低发生率与使用较大原发部位或后颅窝增大体积的先前研究相当。MB亚组不同的解剖失败模式表明，应考虑亚组特异性治疗策略。
