Phase II Trial of Pathology-Based Tripartite Treatment Stratification for Patients with CNS Germ Cell Tumors: A Long-Term Follow-Up Study

Neurology Neurosurgery Oncology Medicine
CNS germ cell tumors long-term follow-up tripartite treatment pathology survival rates relapse complications

Long-Term Follow-Up Study of Central Nervous System Germ Cell Tumors: Pathology-Based Tripartite Treatment Stratification

Academic Background

Central nervous system germ cell tumors (CNS GCTs) are rare tumors primarily occurring in adolescents, especially males aged 12 to 16. These tumors are believed to originate from primordial germ cells (PGCs), which deviate from their normal migratory path during embryonic development, eventually forming tumors in the central nervous system. The diagnosis of CNS GCTs relies on clinical presentation, imaging studies, and tumor markers such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). Despite recent advancements in treatment, managing CNS GCTs remains challenging, particularly in balancing therapeutic efficacy with long-term side effects.

From 1995 to 2003, a multicenter phase II clinical trial was conducted in Japan to evaluate the long-term efficacy and complications of CNS GCTs using a pathology-based tripartite treatment stratification (Germinoma, Intermediate Prognosis Group, and Poor Prognosis Group). However, comprehensive long-term follow-up data from this trial had not been thoroughly analyzed. Therefore, the primary objective of this study was to assess the effectiveness of standardized treatment regimens over the long term and to analyze treatment-related long-term complications.

Source of the Paper

This paper was authored by Hirokazu Takami and colleagues from several renowned institutions in Japan, including the University of Tokyo Hospital and Saitama Medical University International Medical Center. The paper was published in Neuro-Oncology in March 2025, titled “Phase II Trial of Pathology-Based Tripartite Treatment Stratification for Patients with CNS Germ Cell Tumors: A Long-Term Follow-Up Study.”

Research Process

Study Subjects and Grouping

The study included 228 patients with CNS GCTs, divided into three groups based on pathological diagnosis: 1. Germinoma Group (n=161): Included pure Germinoma and Germinoma with syncytiotrophoblastic giant cells (STGC). 2. Intermediate Prognosis Group (n=38): Included Germinoma with STGC, immature teratoma (IMT), teratoma with malignant transformation, and mixed tumors predominantly composed of Germinoma or teratoma. 3. Poor Prognosis Group (n=28): Included choriocarcinoma (CC), yolk sac tumor (YST), embryonal carcinoma (EC), and mixed tumors mainly composed of these malignant elements.

Treatment Regimens

Patients in each group received different chemotherapy and radiotherapy regimens: - Germinoma Group: Received three cycles of carboplatin and etoposide (CARE) chemotherapy, followed by 24 Gy of local radiotherapy. - Intermediate Prognosis Group: Received three cycles of CARE chemotherapy, followed by 30 Gy of local radiotherapy, and then five cycles of CARE chemotherapy. - Poor Prognosis Group: Received ifosfamide, cisplatin, and etoposide (ICE) chemotherapy, followed by 30 Gy of craniospinal irradiation (CSI), and then five cycles of ICE chemotherapy.

Follow-Up and Data Analysis

The research team conducted a long-term follow-up with a median duration of 18.5 years, recording data on recurrence, survival rates, and treatment-related complications. Data analysis employed statistical methods such as the Wilcoxon test, Pearson chi-square test, and multivariate Cox regression analysis.

Key Findings

Treatment Efficacy

  • Germinoma Group: The 10-year and 20-year event-free survival (EFS) rates were 82% and 73%, respectively, while the overall survival (OS) rates were 97% and 92%.
  • Intermediate Prognosis Group: The 10-year and 20-year EFS rates were 76% and 66%, respectively, while the OS rates were 87% and 70%.
  • Poor Prognosis Group: The 10-year and 20-year EFS and OS rates were both 49% and 53%.

Recurrence and Complications

  • Germinoma Group: Recurrence occurred in 35 patients, with recurrence times ranging from 10 months to 325 months. Recurrence sites were mostly in the ventricles and spinal cord.
  • Treatment-Related Complications: Nineteen complications occurred in 16 patients, with cumulative complication rates of 1.9% at 10 years and 11.3% at 20 years.

Causes of Death

  • Germinoma Group: Causes of death varied, including disease progression and treatment-related complications such as pituitary insufficiency.
  • Poor Prognosis Group: Deaths were primarily related to disease progression.

Conclusions and Significance

This study demonstrates the significant value of pathology-based tripartite treatment stratification in the long-term management of CNS GCTs. While Germinoma patients showed high survival rates, the recurrence rates and incidence of treatment-related complications cannot be overlooked. For patients in the Poor Prognosis Group, current treatment regimens are limited in efficacy, and more effective therapeutic approaches need to be explored in the future. Additionally, the study emphasizes the importance of long-term follow-up, particularly in monitoring recurrence and complications.

Research Highlights

  1. Long-Term Follow-Up Data: This study provides 20-year follow-up data for CNS GCT patients, filling a gap in long-term efficacy and complication data in this field.
  2. Pathology-Based Stratified Treatment: By categorizing patients into three groups based on pathological diagnosis, the study provides a basis for personalized treatment.
  3. Detailed Analysis of Recurrence and Complications: The study meticulously records the timing, sites of recurrence, and incidence of treatment-related complications, offering valuable insights for optimizing future treatment strategies.

Other Valuable Information

  • Special Considerations for Basal Ganglia Germinoma: The study found that patients with Basal Ganglia Germinoma had a higher recurrence rate after local radiotherapy, while whole-brain radiotherapy (WBRT) effectively prevented recurrence.
  • Treatment After Recurrence: The study showed that patients who received chemotherapy and radiotherapy after recurrence had significantly higher survival rates than those who received chemotherapy alone.

This study provides critical clinical evidence for the long-term management of CNS GCTs and offers direction for optimizing future treatment strategies.