Prior Daniel, Yang Jingye, Nuño Michelle M, Shaikh Furqan, Frazier A Lindsay, Pashankar Farzana
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Children's Oncology Group, Monrovia, California, USA.
Pediatr Blood Cancer. 2025 Jun;72(6):e31665. doi: 10.1002/pbc.31665. Epub 2025 Mar 17.
Cisplatin, etoposide, and bleomycin (PEb) have been the standard of care for patients with germ cell tumors (GCT). In the 1990s, an intergroup trial (POG9049/CCG8882) randomized patients with high-risk GCT, as defined by the 1990 criteria, to high-dose (HDPEb) versus standard-dose PEb. HDPEb resulted in improved event-free survival (EFS), but no difference in overall survival (OS), thus standard-dose PEb has remained the standard of care. Subsequently, the Malignant Germ Cell International Consortium (MaGIC) updated the risk stratification for pediatric and adolescent patients with GCT. Currently, patients are categorized as intermediate or poor risk if they are ≥11 years of age with Stage IV ovarian GCT, or testicular, mediastinal, or retroperitoneal GCT with intermediate or poor prognosis using the International Germ Cell Consensus Classification criteria.
We re-analyzed data from the POG9049/CCG8882 trial using the updated MaGIC risk stratification to determine whether HDPEb improved outcomes over PEb in patients with intermediate/poor-risk GCTs.
Among 299 patients in the trial, 57 patients (48 males, nine females) met the inclusion criteria for this analysis. There were no statistically significant differences in 5-year EFS (0.72 vs. 0.70, p-value = 0.82) or OS (0.76 vs. 0.74, p-value = 0.91) among patients treated with HDPEb versus PEb, respectively. Also, of note patients with mediastinal primaries had significantly worse 5-year EFS (0.51 vs. 0.83, p-value = 0.0062) and OS (0.49 vs. 0.89, p-value = 0.0013) compared to other sites, with no difference in outcome between HDPEb and PEb.
Treatment with HDPEb did not improve outcomes for intermediate/poor-risk GCT patients compared to standard-dose PEb.
顺铂、依托泊苷和博来霉素（PEb）一直是生殖细胞肿瘤（GCT）患者的标准治疗方案。在20世纪90年代，一项多组间试验（POG9049/CCG8882）将按照1990年标准定义的高危GCT患者随机分为接受高剂量（HDPEb）与标准剂量PEb治疗两组。高剂量PEb提高了无事件生存期（EFS），但总生存期（OS）无差异，因此标准剂量PEb仍然是标准治疗方案。随后，恶性生殖细胞国际联盟（MaGIC）更新了儿童和青少年GCT患者的风险分层。目前，如果患者年龄≥11岁，患有IV期卵巢GCT，或根据国际生殖细胞共识分类标准预后为中度或不良的睾丸、纵隔或腹膜后GCT，则被归类为中度或高危。
我们使用更新后的MaGIC风险分层重新分析了POG9049/CCG8882试验的数据，以确定在中度/高危GCT患者中，HDPEb与PEb相比是否能改善治疗结果。
在该试验的299例患者中，57例患者（48例男性，9例女性）符合本分析的纳入标准。接受HDPEb与PEb治疗的患者，其5年EFS（分别为0.72对0.70，p值 = 0.82）或OS（分别为0.76对0.74，p值 = 0.91）无统计学显著差异。此外，值得注意的是，与其他部位相比，纵隔原发性肿瘤患者的5年EFS（0.51对0.83，p值 = 0.0062）和OS（0.49对0.89，p值 = 0.0013）明显更差，HDPEb与PEb之间的治疗结果无差异。
与标准剂量PEb相比，高剂量PEb治疗并未改善中度/高危GCT患者的治疗结果。
