Chemotherapy Followed by Radiation Therapy

A Children's Oncology Group (COG) study (ACNS0122 [NCT00047320]) evaluated neoadjuvant chemotherapy followed by radiation therapy for children with localized NGGCTs.[2] Neoadjuvant chemotherapy consisted of six courses with carboplatin/etoposide alternating with ifosfamide/etoposide. After chemotherapy was completed, responding patients received 36 Gy of craniospinal radiation therapy, with 54 Gy to the tumor bed.

A Children's Oncology Group (COG) study (ACNS0122 [NCT00047320]) evaluated neoadjuvant chemotherapy followed by radiation therapy for children with localized NGGCTs.[2] Neoadjuvant chemotherapy consisted of six courses with carboplatin/etoposide alternating with ifosfamide/etoposide. After chemotherapy was completed, responding patients received 36 Gy of craniospinal radiation therapy, with 54 Gy to the tumor bed.

On the basis of a central review, 87% of patients showed either partial response (PR) or complete response (CR).

A Children's Oncology Group (COG) study (ACNS0122 [NCT00047320]) evaluated neoadjuvant chemotherapy followed by radiation therapy for children with localized NGGCTs.[2] Neoadjuvant chemotherapy consisted of six courses with carboplatin/etoposide alternating with ifosfamide/etoposide. After chemotherapy was completed, responding patients received 36 Gy of craniospinal radiation therapy, with 54 Gy to the tumor bed.

For the 102 eligible patients in the study, the 5-year event-free survival (EFS) rate was 84% (± 4%), and the OS rate was 93% (± 3%).

A Children's Oncology Group (COG) study (ACNS0122 [NCT00047320]) evaluated neoadjuvant chemotherapy followed by radiation therapy for children with localized NGGCTs.[2] Neoadjuvant chemotherapy consisted of six courses with carboplatin/etoposide alternating with ifosfamide/etoposide. After chemotherapy was completed, responding patients received 36 Gy of craniospinal radiation therapy, with 54 Gy to the tumor bed.

At 3 years, the EFS rate was 92% and the OS rate was 98% for all patients who achieved CR or PR either after induction chemotherapy or with the absence of malignant elements documented during second-look surgery.

The European SIOP-CNS-GCT-96 (NCT00293358) trial evaluated neoadjuvant chemotherapy consisting of four courses with cisplatin/etoposide/ifosfamide followed by focal radiation therapy (54 Gy) for patients with nonmetastatic disease.[3]

The European SIOP-CNS-GCT-96 (NCT00293358) trial evaluated neoadjuvant chemotherapy consisting of four courses with cisplatin/etoposide/ifosfamide followed by focal radiation therapy (54 Gy) for patients with nonmetastatic disease.[3]

Patients with localized tumors (n = 116) demonstrated 5-year progression-free survival (PFS) rates of 72% (± 4%) and OS rates of 82% (± 4%).

Stratum 1 of the COG ACNS1123 (NCT01602666) study evaluated the efficacy of reduced-dose and reduced-volume radiation therapy in children and adolescents with localized NGGCTs who achieved PRs, CRs, and marker normalization after six cycles of chemotherapy. The main objective of this study was to evaluate the impact of reduced radiation therapy on PFS, with a goal of preserving neurocognitive function. Isolated spinal relapses occurred in 10% of patients in this trial, causing early stoppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the ACNS0122 (NCT00047320) trial. Patients in this study received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide. If a CR or PR with or without second-look surgery was achieved, the patient was eligible for reduced radiation therapy, defined as 30.6 Gy to the whole-ventricular field and a 54-Gy boost to the tumor bed, compared with 36 Gy of craniospinal irradiation plus a 54-Gy tumor-bed boost used in the ACNS0122 trial.[4,10]

Stratum 1 of the COG ACNS1123 (NCT01602666) study evaluated the efficacy of reduced-dose and reduced-volume radiation therapy in children and adolescents with localized NGGCTs who achieved PRs, CRs, and marker normalization after six cycles of chemotherapy. The main objective of this study was to evaluate the impact of reduced radiation therapy on PFS, with a goal of preserving neurocognitive function. Isolated spinal relapses occurred in 10% of patients in this trial, causing early stoppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the ACNS0122 (NCT00047320) trial. Patients in this study received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide. If a CR or PR with or without second-look surgery was achieved, the patient was eligible for reduced radiation therapy, defined as 30.6 Gy to the whole-ventricular field and a 54-Gy boost to the tumor bed, compared with 36 Gy of craniospinal irradiation plus a 54-Gy tumor-bed boost used in the ACNS0122 trial.[4,10]

Of the 107 patients enrolled, 66 (61.7%) achieved a CR or PR and received reduced radiation therapy. The 3-year PFS rate was 87.8% (± 4.04%), and the OS rate was 92.4% (± 3.3%).

Stratum 1 of the COG ACNS1123 (NCT01602666) study evaluated the efficacy of reduced-dose and reduced-volume radiation therapy in children and adolescents with localized NGGCTs who achieved PRs, CRs, and marker normalization after six cycles of chemotherapy. The main objective of this study was to evaluate the impact of reduced radiation therapy on PFS, with a goal of preserving neurocognitive function. Isolated spinal relapses occurred in 10% of patients in this trial, causing early stoppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the ACNS0122 (NCT00047320) trial. Patients in this study received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide. If a CR or PR with or without second-look surgery was achieved, the patient was eligible for reduced radiation therapy, defined as 30.6 Gy to the whole-ventricular field and a 54-Gy boost to the tumor bed, compared with 36 Gy of craniospinal irradiation plus a 54-Gy tumor-bed boost used in the ACNS0122 trial.[4,10]

There were eight documented recurrences; six patients had distant spinal relapse alone and two patients had combined local-plus-distant relapse.

Stratum 1 of the COG ACNS1123 (NCT01602666) study evaluated the efficacy of reduced-dose and reduced-volume radiation therapy in children and adolescents with localized NGGCTs who achieved PRs, CRs, and marker normalization after six cycles of chemotherapy. The main objective of this study was to evaluate the impact of reduced radiation therapy on PFS, with a goal of preserving neurocognitive function. Isolated spinal relapses occurred in 10% of patients in this trial, causing early stoppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the ACNS0122 (NCT00047320) trial. Patients in this study received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide. If a CR or PR with or without second-look surgery was achieved, the patient was eligible for reduced radiation therapy, defined as 30.6 Gy to the whole-ventricular field and a 54-Gy boost to the tumor bed, compared with 36 Gy of craniospinal irradiation plus a 54-Gy tumor-bed boost used in the ACNS0122 trial.[4,10]

Patients with localized NGGCTs who achieved a CR or PR with chemotherapy and received reduced radiation therapy had a good PFS rate, similar to patients in the ACNS0122 trial who received craniospinal irradiation.

Stratum 1 of the COG ACNS1123 (NCT01602666) study evaluated the efficacy of reduced-dose and reduced-volume radiation therapy in children and adolescents with localized NGGCTs who achieved PRs, CRs, and marker normalization after six cycles of chemotherapy. The main objective of this study was to evaluate the impact of reduced radiation therapy on PFS, with a goal of preserving neurocognitive function. Isolated spinal relapses occurred in 10% of patients in this trial, causing early stoppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the ACNS0122 (NCT00047320) trial. Patients in this study received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide. If a CR or PR with or without second-look surgery was achieved, the patient was eligible for reduced radiation therapy, defined as 30.6 Gy to the whole-ventricular field and a 54-Gy boost to the tumor bed, compared with 36 Gy of craniospinal irradiation plus a 54-Gy tumor-bed boost used in the ACNS0122 trial.[4,10]

There was no significant difference in survival rates for NGGCT patients with localized disease in the two COG studies. The predominant site of relapse for patients in the ACNS1123 trial was in the spine, which was unique.[2,4]

Stratum 1 of the COG ACNS1123 (NCT01602666) study evaluated the efficacy of reduced-dose and reduced-volume radiation therapy in children and adolescents with localized NGGCTs who achieved PRs, CRs, and marker normalization after six cycles of chemotherapy. The main objective of this study was to evaluate the impact of reduced radiation therapy on PFS, with a goal of preserving neurocognitive function. Isolated spinal relapses occurred in 10% of patients in this trial, causing early stoppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the ACNS0122 (NCT00047320) trial. Patients in this study received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide. If a CR or PR with or without second-look surgery was achieved, the patient was eligible for reduced radiation therapy, defined as 30.6 Gy to the whole-ventricular field and a 54-Gy boost to the tumor bed, compared with 36 Gy of craniospinal irradiation plus a 54-Gy tumor-bed boost used in the ACNS0122 trial.[4,10]

A subgroup analysis compared protons with photons to the whole ventricles for treating patients with NGGCTs.[11] Mean radiation doses and the doses to 40% of volumes, including the supratentorial brain, cerebellum, bilateral temporal, parietal, and frontal lobes, were significantly lower among patients who were treated with protons than patients who were treated with photons. Late effects data confirming a clinical benefit are not available.