- Email: [email protected]
Outcome for children with high stage medulloblastoma: Results of the pediatric oncology group 9031
Proceedings
of the 42nd Annual ASTRO Meeting
179
Materials and Methods: Patients are treated according to stage of disease (CS) in 3 treatment groups (TG 1: CS IiIIA, TC 2: CS IIAE/B, IIIA, TG 3: CS IIBE, IIIAE/B, IV) with 2. 4 or 6 cycles combination chemotherapy (2 cycles OEPA or OPPA ? 2 or 4 cycles of COPP). When a complete remission (CR) is achieved treatment will be terminated without RT; patients with a partial remission (PR) of >75% tumor regression will be irradiated with 20 Gy to modified involved fields, PR of <75% with 30 CY, residual masses of >50 ml up to 35 Gy. Results: From August 1995 a total of 703 patients have been registered, 39% in TG I, 27% in TG 2, 34% in TG 3.651 finished treatment until March 2000 and were evaluable, median follow-up time is 27 months. Chemotherapy resulted in CR in 22% (147 pts.), PR > 75% in 61%, PR < 75% in 12%; 6 pts. with lymphocytic predominance, nodular subtype were in CR after surgery and did not get further treatment. Event free survival (EFS) is 90%, overall survival 98% (Kaplan-Meier-analysis); EFS with RT is 92%. without RT 85% (p = 0.22). in TGI 92% and 97%, resp. (p = 0.27) in TG2 94% and 65% (p = 0.006) in TG3 92% and 80% (p = 0.27). The ‘significant’ difference in TG2 is due to one late event. -50 events were observed: I1 tumor progressions during primary treatment, 35 relapses. 1 fatal infection, 1 second malignancy after 14 months and 2 unrelated fatal accidents. 22 relapses (4,5%x) were observed in the group of 492 pts. with RT, 13 (9%) in 147 pts. without RT.17/35 relapses occured during the first 6 months after the end of treatment, 28 (80%) within 12 months.- In the irradiated group 5/22 relapses were located within the treatment iields, 7 outside or disseminated, 10 in and outside, as well. 4 local relapses were probably due to insufficient RT-techniques. All 13 relapses of the not irradiated group occured in initially involved regions, 6 in other areas additionally. Conclusions: Results of the ongoing HD95 protocol are excellent until now and comparable to those of the previous trials using higher RT doses and larger volumes. The somewhat higher incidence of relapses in the non-irradiated group is not yet significant and does not impair survival rates. Follow-up time is too short to evaluate the influence on long term toxicity. The trial will be continued.
134
Outcome for children with high stage medulloblastoma:
N. .I. Tarbell,’
H. Friedman,’
J. Kepner,’
P. Barnes,” P. Burger,’
Results of the pediatric oncology group 9031
L. E. Kunh
‘Mmwchusetts General Hospital, Boston, MA, ‘Duke Universityg Medical Center, Durham, NC, ‘Univer,rity of Florida Gainesville, FL, “Children’s Hospital, Boston, MA, ‘Johns Hopkins, Bultimore, MD, “St. Jude Childrens Research Hospital, Memphis, TN
Purpose: To compare the 2 year event free survival (EFS) of children with newly diagnosed randomized to receive chemotherapy pre-irradiation vs. chemotherapy after irradiation.
high risk medulloblastoma
Materials & Methods: Patients were enrolled in POG 9031 and randomized after surgery to receive either Treatment(TX)Ol consisting of 3 courses of cisplatin 90 mg/m’ and etoposide (150 mg/m’) as pre-irradiation chemotherapy (CT) or Treatment (TX)02 which consisted of radiation first and included craniospinal irradiation (CSI) plus a posterior-fossa (PF) boost. Radiation therapy (RT) started at week IO and was given as 18 Gy/fraction. The CSI dose for M,-M, patients was 35.2 Gy and 40 Gy CSI for MZ-M, patients. The total dose to the PF was 55.8 Gy. All patients received CT 3 weeks after completion of RT. For TX01 patients received post-RT CT consisting of vincristine (V) 2 mg/m’ and cyclophosphemide (C) loo0 mg/m’ with MESNA. For TX02. patients received all CT after RT (cisplatin, etoposide followed by VC). The duration of TX was one year. Eligibility included age >3 and 521 years. High stage medulloblastoma was defined as one or more of the following: 1) T,, or T+ 2) > 15 cm residual tumor on post CT or MRI, or 3) CNS metastasis (M ,-M,). Results: 226 eligible patients were randomized from 1990-1996. There were 133 males and 93 females. Patients M stage was as follows: M, = 113. M, = 29, M, = 34, M, = 32, M, = 8. For 12 patients, M stage was not recorded. 114 patients received TX01 112 patients received TX02. With a medium follow up of 4.5 years, 2 years EFS was 78% (S.E. = 3.9%) and 80% (SE. = 3.9%) respectively. The overall 2-year survival was 83% (SE. = 3.6%) and 90% (SE. = 3%) respectively. Using one-sided logrank tests. there was insufficient evidence to conclude that (1) the EFS curves for the two txs are different (p = 0.239) and (2) the survival curves for the two txs are different (p - 0.382). The 2 year EFS for M,-M, patients was 61% (S.E. = 6.8%)in the CT first arm (TXOI) vs 74% (S.E. = 6.5%) in the RT first arm (TX02). (p = ns) Toxicity consisted primarily of myelosuppresaion. There have been 2 second malignancies, one in each treatment arm and both were myelodysplastic syndrome (MDS). Conclusions: There was no statistically significant difference in those patients randomized to receive chemotherapy first (Treatment 01) vs. those patients who were randomized to receive radiation first (Treatment 02). Overall, survival in this group of patients with high staged medulloblastoma compares favorably with that seen in previous studies.
135
C om b’me d pos toperative therapy for supratentorial primitive of the German prospective trial hit’88/89 and hit’91
B. Timmermann,’
R. D. Kortmann,’
_I. Ktihl,’ C. Meisner,’
K. Dieckmann,’
neuroectodermal
tumors in childhood:
Results
M. Bamberg’
‘Dept. Qf Radiooncology, University of Tiibingen, Tiibingerl, Germcmy, 'Childrerz‘s Hospital, University of Wiir,-burg, WiA’rzburg. Germtrny, ‘Institute of Mediccd Informatiorl Processing, University of Tiibiqen, Tiibingen, Germany, ‘Dept. Rrrdiooncology, General Hospital, Vienna, Austria
Purpose: irradiation
I To evaluate the outcome in children with supratentorial and chemotherapy.
2. To identify factors predictive
PNET’s (primitive neuroectodermal for survival.
of
tumors) after surgery,
Materials and Methods: Eligible were 44 children with newly diagnosed PNET’s, who were treated in the multicenter prospective trials HIT 88/89 and HIT 91 between 1988 and 1997. Median age of 16 girls and 28 boys at diagnosis was 6.2 years. In 3 children the investigation of the cerebrospinal fluid was positive and in 6 children solid metastases within the central nervous system (CNS) were found. Macroscopic complete resection was achieved in 15 patients (pts.). 29 pts. underwent incomplete resection. All pts. received chemotherapy, in 31 patients before irradiation consisting of 2 cycles of cisplatin, ifosfamide, etoposide, cytarabine methotrexate. In 13 children the chemotherapy was administered after irradiation with 8
of the 42nd Annual ASTRO Meeting
179
Materials and Methods: Patients are treated according to stage of disease (CS) in 3 treatment groups (TG 1: CS IiIIA, TC 2: CS IIAE/B, IIIA, TG 3: CS IIBE, IIIAE/B, IV) with 2. 4 or 6 cycles combination chemotherapy (2 cycles OEPA or OPPA ? 2 or 4 cycles of COPP). When a complete remission (CR) is achieved treatment will be terminated without RT; patients with a partial remission (PR) of >75% tumor regression will be irradiated with 20 Gy to modified involved fields, PR of <75% with 30 CY, residual masses of >50 ml up to 35 Gy. Results: From August 1995 a total of 703 patients have been registered, 39% in TG I, 27% in TG 2, 34% in TG 3.651 finished treatment until March 2000 and were evaluable, median follow-up time is 27 months. Chemotherapy resulted in CR in 22% (147 pts.), PR > 75% in 61%, PR < 75% in 12%; 6 pts. with lymphocytic predominance, nodular subtype were in CR after surgery and did not get further treatment. Event free survival (EFS) is 90%, overall survival 98% (Kaplan-Meier-analysis); EFS with RT is 92%. without RT 85% (p = 0.22). in TGI 92% and 97%, resp. (p = 0.27) in TG2 94% and 65% (p = 0.006) in TG3 92% and 80% (p = 0.27). The ‘significant’ difference in TG2 is due to one late event. -50 events were observed: I1 tumor progressions during primary treatment, 35 relapses. 1 fatal infection, 1 second malignancy after 14 months and 2 unrelated fatal accidents. 22 relapses (4,5%x) were observed in the group of 492 pts. with RT, 13 (9%) in 147 pts. without RT.17/35 relapses occured during the first 6 months after the end of treatment, 28 (80%) within 12 months.- In the irradiated group 5/22 relapses were located within the treatment iields, 7 outside or disseminated, 10 in and outside, as well. 4 local relapses were probably due to insufficient RT-techniques. All 13 relapses of the not irradiated group occured in initially involved regions, 6 in other areas additionally. Conclusions: Results of the ongoing HD95 protocol are excellent until now and comparable to those of the previous trials using higher RT doses and larger volumes. The somewhat higher incidence of relapses in the non-irradiated group is not yet significant and does not impair survival rates. Follow-up time is too short to evaluate the influence on long term toxicity. The trial will be continued.
134
Outcome for children with high stage medulloblastoma:
N. .I. Tarbell,’
H. Friedman,’
J. Kepner,’
P. Barnes,” P. Burger,’
Results of the pediatric oncology group 9031
L. E. Kunh
‘Mmwchusetts General Hospital, Boston, MA, ‘Duke Universityg Medical Center, Durham, NC, ‘Univer,rity of Florida Gainesville, FL, “Children’s Hospital, Boston, MA, ‘Johns Hopkins, Bultimore, MD, “St. Jude Childrens Research Hospital, Memphis, TN
Purpose: To compare the 2 year event free survival (EFS) of children with newly diagnosed randomized to receive chemotherapy pre-irradiation vs. chemotherapy after irradiation.
high risk medulloblastoma
Materials & Methods: Patients were enrolled in POG 9031 and randomized after surgery to receive either Treatment(TX)Ol consisting of 3 courses of cisplatin 90 mg/m’ and etoposide (150 mg/m’) as pre-irradiation chemotherapy (CT) or Treatment (TX)02 which consisted of radiation first and included craniospinal irradiation (CSI) plus a posterior-fossa (PF) boost. Radiation therapy (RT) started at week IO and was given as 18 Gy/fraction. The CSI dose for M,-M, patients was 35.2 Gy and 40 Gy CSI for MZ-M, patients. The total dose to the PF was 55.8 Gy. All patients received CT 3 weeks after completion of RT. For TX01 patients received post-RT CT consisting of vincristine (V) 2 mg/m’ and cyclophosphemide (C) loo0 mg/m’ with MESNA. For TX02. patients received all CT after RT (cisplatin, etoposide followed by VC). The duration of TX was one year. Eligibility included age >3 and 521 years. High stage medulloblastoma was defined as one or more of the following: 1) T,, or T+ 2) > 15 cm residual tumor on post CT or MRI, or 3) CNS metastasis (M ,-M,). Results: 226 eligible patients were randomized from 1990-1996. There were 133 males and 93 females. Patients M stage was as follows: M, = 113. M, = 29, M, = 34, M, = 32, M, = 8. For 12 patients, M stage was not recorded. 114 patients received TX01 112 patients received TX02. With a medium follow up of 4.5 years, 2 years EFS was 78% (S.E. = 3.9%) and 80% (SE. = 3.9%) respectively. The overall 2-year survival was 83% (SE. = 3.6%) and 90% (SE. = 3%) respectively. Using one-sided logrank tests. there was insufficient evidence to conclude that (1) the EFS curves for the two txs are different (p = 0.239) and (2) the survival curves for the two txs are different (p - 0.382). The 2 year EFS for M,-M, patients was 61% (S.E. = 6.8%)in the CT first arm (TXOI) vs 74% (S.E. = 6.5%) in the RT first arm (TX02). (p = ns) Toxicity consisted primarily of myelosuppresaion. There have been 2 second malignancies, one in each treatment arm and both were myelodysplastic syndrome (MDS). Conclusions: There was no statistically significant difference in those patients randomized to receive chemotherapy first (Treatment 01) vs. those patients who were randomized to receive radiation first (Treatment 02). Overall, survival in this group of patients with high staged medulloblastoma compares favorably with that seen in previous studies.
135
C om b’me d pos toperative therapy for supratentorial primitive of the German prospective trial hit’88/89 and hit’91
B. Timmermann,’
R. D. Kortmann,’
_I. Ktihl,’ C. Meisner,’
K. Dieckmann,’
neuroectodermal
tumors in childhood:
Results
M. Bamberg’
‘Dept. Qf Radiooncology, University of Tiibingen, Tiibingerl, Germcmy, 'Childrerz‘s Hospital, University of Wiir,-burg, WiA’rzburg. Germtrny, ‘Institute of Mediccd Informatiorl Processing, University of Tiibiqen, Tiibingen, Germany, ‘Dept. Rrrdiooncology, General Hospital, Vienna, Austria
Purpose: irradiation
I To evaluate the outcome in children with supratentorial and chemotherapy.
2. To identify factors predictive
PNET’s (primitive neuroectodermal for survival.
of
tumors) after surgery,
Materials and Methods: Eligible were 44 children with newly diagnosed PNET’s, who were treated in the multicenter prospective trials HIT 88/89 and HIT 91 between 1988 and 1997. Median age of 16 girls and 28 boys at diagnosis was 6.2 years. In 3 children the investigation of the cerebrospinal fluid was positive and in 6 children solid metastases within the central nervous system (CNS) were found. Macroscopic complete resection was achieved in 15 patients (pts.). 29 pts. underwent incomplete resection. All pts. received chemotherapy, in 31 patients before irradiation consisting of 2 cycles of cisplatin, ifosfamide, etoposide, cytarabine methotrexate. In 13 children the chemotherapy was administered after irradiation with 8