- Email: [email protected]
The impact of multiple post-operative factors on neuro-cognitive function in children treated with radiation therapy for medulloblastoma
225
Proceedings of the 34th Annual ASTRO Meeting
169 20 YEAR EXPERIENCE IN CHILDHOOD CRANIOPHARYNGIOMA: THE IMPORTANCE OF RADIATION THERAPY Stella Hetelekidis, M.D.‘, May L. Tao l, Edwin G. Fischer, M.D.4, Patrick D. Barnes, M.D.2, R. Michael Scott. M.D.3,and Nancy J. Tarbell, M.D.’ Joint Center for Radiation Therapy’, Departments of Radiology2 and Neurosurgery3, Children’s Hospital, and Department of Neurosurgery, New England Deaconess Hospita14, Harvard Medical School, Boston, MA. Purpose: The management of craniopharyngioma is controversial, and surgery alone is frequently advocated. of this study was to assess the long-term impact of various treatments in childhood craniopharyngioma.
The purpose
Materials and Methods: Fifty-nine children 521 years were treated al the Joint Center for Radiation Therapy and Children’s Hospital from 1970 to 1990. The median age was 7.5 years (range 10 months - 21 years). There were 32 females and 27 males, and the median follow-up (F/U) was 123 months (range 20-253 months). Nine children were treated with radiotherapy alone (RT), 14 were treated with surgery alone (S), and 36 were treated with both surgery and radiotherapy (S+RT). All patients in the RT and S+RT groups underwent treatment simulation, and were treated with megavoltage RT with a median dose of 5470 cGy (range 5050-6596 cGy). Results: All nine of the children treated with RT only ate alive with a median F/U of 141 months. None have recurred. Nine of 14 children treated with S alone have recurred (p=O.O066 Fisher exact test, median F/U 116 months). Five of these patients are alive with disease (ACD), and 4 are alive without disease (ASD) after treatment with RT at relapse. Seven of 36 patients treated with S+RT have recurred (median F/U 123 months). Three of 7 patients ultimately died of their disease, three patients are ACD, and 1 patient is ASD after further surgery. The IO-year actuarial overall survival was 91% for all patients. The IO-vear actuarial freedom from orooression (FFP) for the -.S group was 32% compared with 100% for patients treated with’ RT only (log rank p=O.O04),’a& 86% for patients treated with S+RT at diagnosis (p=O.OOl). There was no significant difference in the incidence of major side effects such as blindness, seizures, and hormonal abnormalities among the three groups. There were two treatment related deaths, both in the S+RT group. One patient died of metabolic complications 13 months after S, and another developed an in-field glioma 93 months after RT. One patient developed Moyamoya syndrome 75 months after S and RT. Conclusion: Overall survival in childhood craniopharyngioma is excellent. However, patients treated with surgery alone have a significantly worse freedom from progression when compared to patients treated with surgery and radiation therapy, or radiation therapy alone.
170 PREDICTIVE ASSJiYs IN HEEuUOBL&sTOMA HM Fagundes’, %adiation
R Higashikubo’,
Oncology
Center,
PE Swanson’, ‘Pathology
JR Simpsonl,
Department,
JM Michalski’,
Washington
University
N Kucikl School
of Medicine,
St.
Louis,
MO
-E: The purpose of this analysis was to search for predictive assays for characterizing medulloblastomas, and predicting the prognosis of patients with these tumors independent of conventional clinical and histological assessment in an attempt to identify a subgroup at higher risk who could benefit from more aggressive initial therapy. mTEZUAtSANDMETBoDs: lVenty-eight patients were evaluated by immunohistochemistry and flow cytometric analysis performed independently without knowledge of patient outcome. Paraffin sections were stained with monoclonal antibodies to synaptophysin and desmin. Flow cytometric measurements included ploidy and DNA p-53, and %S + G2 phase. index, antioncogene AU patients had received standard treatment (dehulking surgery and postoperative craniospinal radiation). The outcome of these patients was analyzed and correlated in terms of local control, relapse-free survival, and overall survival with imohistochemistry and flow cytometric parameters. RESULTS: Local control at 5 years correlated well with ploidy, and 065 + G2 phase. Patients with tumors having an aneuploid index, %S + G2 phase > 10% and (-) desmin showed considerably poorer local control. P-53 did not correlate with local control. The 5-year disease-free survival showed direct correlation with p-53, and %S + G2 phase, with poorer outcome in patients with (-) p-53, and OS.5+ G2 phase > 10%. Ploidy and desmin did not correlate with disease-free survival. The actuarial overall survival at 5 years was
226
FWation OnCOlOgy,Biology, Physics Volume24,Supplement
worse in patients with aneuploid tumors, correlation of synaptophysin with patient EL!auE
1
I
I
1
6
I
TlYL ,“W‘,
0
I
(-) p-53, %S + G2 phase > 10% and (-) outcome as all tumors were positive.
2 TlYE ,y..‘.)
1
4
s
”
I
1
TlYl
3
4
1 desmin.
I
,I..‘.)
”
There was no
1
‘
,
*
r.3xuus1cNs: The current study suggests that FCM analysis including DNA ploidy, Antioncogene p-53, + G2 phase as well as innnunohistochemistry analysis such as desmin staining may be useful predictive in identifying patients at higher risk for relapse.
and %S assays
171 THE IMPACT OF MULTIPLE CHILDREN TREATED WITH
POST-OPERATIVE FACTORS ON NEURO-COGNITIVE RADIATION THERAPY FOR MEDULLOBLASTOMA
FUNCTION
IN
Gary D. Kao, M.D.‘, Joel Goldwein, M.D. I,, Jerilynn Radcliffe, Ph.D., Guilio D’Angio, M.D.’ 1 Hospital of the University of Pennsylvania Department of Radiation Oncology, Phila., PA 2The Children’s Seashore House, Children’s Hospital of Philadelphia, Phila., PA
Purpose: To determine the significance of post-operative neurocognitive deterioration in children with medulloblastoma treated or without chemotherapy.
factors on subsequent with radiation therapy
with
The medical charts of 28 children who have undergone prospective Materials and Methods: and serial neurocognitive testing were reviewed. All children received radiotherapy with/without chemotherapy for non-metastatic medulloblastoma and are disease-free for intervals between 1.2 and 6 years. The mean and median age at diagnosis were respectively 6.9 and 6.8 years (range 1.5 16.5 years). The mean and median followup were respectively 3.5 and 3 years (range: l-6 years). The clinical courses of the patients were then correlated with the absolute and change in the quotients (FSIQ) of each child before and after radiation therapy. respective full scale intelligence Eight of the 28 children had post-operative cranial nerve deficits or Results: hemiparesis, 6 had meningitis, 5 had subdural hematomas requiring evacuation, and 9 required multiple cranial procedures for shunt revision, emergent shunt placement, or scar excision. Of the subset of children with one or more of these factors, 13/1E (81%) sustained decreases in full-scale IQ (FSIQ) > 5 points, and 6 (37.5%) of Z- 20 points. By contrast, only 3/12 (25 %) of children without any of the above post-operative complications sustained FSIQ decreases > 5 points. This difference was significant (p = 0.01 via chi-square analysis).
Conclusions:
,
TiME IY..‘.,
Post-operative events or complications may account for some of the neurocognitive deterioration seen in these children after treatment. The occurrence of these factors is associated with significantly greater risk of neurocognitive deterioration. In these children, early detection and remedial intervention may be warranted. Furthermore, studies of the neurocognitive effects of treatment for children with medulloblastoma should include analysis of these post-operative factors.
Proceedings of the 34th Annual ASTRO Meeting
169 20 YEAR EXPERIENCE IN CHILDHOOD CRANIOPHARYNGIOMA: THE IMPORTANCE OF RADIATION THERAPY Stella Hetelekidis, M.D.‘, May L. Tao l, Edwin G. Fischer, M.D.4, Patrick D. Barnes, M.D.2, R. Michael Scott. M.D.3,and Nancy J. Tarbell, M.D.’ Joint Center for Radiation Therapy’, Departments of Radiology2 and Neurosurgery3, Children’s Hospital, and Department of Neurosurgery, New England Deaconess Hospita14, Harvard Medical School, Boston, MA. Purpose: The management of craniopharyngioma is controversial, and surgery alone is frequently advocated. of this study was to assess the long-term impact of various treatments in childhood craniopharyngioma.
The purpose
Materials and Methods: Fifty-nine children 521 years were treated al the Joint Center for Radiation Therapy and Children’s Hospital from 1970 to 1990. The median age was 7.5 years (range 10 months - 21 years). There were 32 females and 27 males, and the median follow-up (F/U) was 123 months (range 20-253 months). Nine children were treated with radiotherapy alone (RT), 14 were treated with surgery alone (S), and 36 were treated with both surgery and radiotherapy (S+RT). All patients in the RT and S+RT groups underwent treatment simulation, and were treated with megavoltage RT with a median dose of 5470 cGy (range 5050-6596 cGy). Results: All nine of the children treated with RT only ate alive with a median F/U of 141 months. None have recurred. Nine of 14 children treated with S alone have recurred (p=O.O066 Fisher exact test, median F/U 116 months). Five of these patients are alive with disease (ACD), and 4 are alive without disease (ASD) after treatment with RT at relapse. Seven of 36 patients treated with S+RT have recurred (median F/U 123 months). Three of 7 patients ultimately died of their disease, three patients are ACD, and 1 patient is ASD after further surgery. The IO-year actuarial overall survival was 91% for all patients. The IO-vear actuarial freedom from orooression (FFP) for the -.S group was 32% compared with 100% for patients treated with’ RT only (log rank p=O.O04),’a& 86% for patients treated with S+RT at diagnosis (p=O.OOl). There was no significant difference in the incidence of major side effects such as blindness, seizures, and hormonal abnormalities among the three groups. There were two treatment related deaths, both in the S+RT group. One patient died of metabolic complications 13 months after S, and another developed an in-field glioma 93 months after RT. One patient developed Moyamoya syndrome 75 months after S and RT. Conclusion: Overall survival in childhood craniopharyngioma is excellent. However, patients treated with surgery alone have a significantly worse freedom from progression when compared to patients treated with surgery and radiation therapy, or radiation therapy alone.
170 PREDICTIVE ASSJiYs IN HEEuUOBL&sTOMA HM Fagundes’, %adiation
R Higashikubo’,
Oncology
Center,
PE Swanson’, ‘Pathology
JR Simpsonl,
Department,
JM Michalski’,
Washington
University
N Kucikl School
of Medicine,
St.
Louis,
MO
-E: The purpose of this analysis was to search for predictive assays for characterizing medulloblastomas, and predicting the prognosis of patients with these tumors independent of conventional clinical and histological assessment in an attempt to identify a subgroup at higher risk who could benefit from more aggressive initial therapy. mTEZUAtSANDMETBoDs: lVenty-eight patients were evaluated by immunohistochemistry and flow cytometric analysis performed independently without knowledge of patient outcome. Paraffin sections were stained with monoclonal antibodies to synaptophysin and desmin. Flow cytometric measurements included ploidy and DNA p-53, and %S + G2 phase. index, antioncogene AU patients had received standard treatment (dehulking surgery and postoperative craniospinal radiation). The outcome of these patients was analyzed and correlated in terms of local control, relapse-free survival, and overall survival with imohistochemistry and flow cytometric parameters. RESULTS: Local control at 5 years correlated well with ploidy, and 065 + G2 phase. Patients with tumors having an aneuploid index, %S + G2 phase > 10% and (-) desmin showed considerably poorer local control. P-53 did not correlate with local control. The 5-year disease-free survival showed direct correlation with p-53, and %S + G2 phase, with poorer outcome in patients with (-) p-53, and OS.5+ G2 phase > 10%. Ploidy and desmin did not correlate with disease-free survival. The actuarial overall survival at 5 years was
226
FWation OnCOlOgy,Biology, Physics Volume24,Supplement
worse in patients with aneuploid tumors, correlation of synaptophysin with patient EL!auE
1
I
I
1
6
I
TlYL ,“W‘,
0
I
(-) p-53, %S + G2 phase > 10% and (-) outcome as all tumors were positive.
2 TlYE ,y..‘.)
1
4
s
”
I
1
TlYl
3
4
1 desmin.
I
,I..‘.)
”
There was no
1
‘
,
*
r.3xuus1cNs: The current study suggests that FCM analysis including DNA ploidy, Antioncogene p-53, + G2 phase as well as innnunohistochemistry analysis such as desmin staining may be useful predictive in identifying patients at higher risk for relapse.
and %S assays
171 THE IMPACT OF MULTIPLE CHILDREN TREATED WITH
POST-OPERATIVE FACTORS ON NEURO-COGNITIVE RADIATION THERAPY FOR MEDULLOBLASTOMA
FUNCTION
IN
Gary D. Kao, M.D.‘, Joel Goldwein, M.D. I,, Jerilynn Radcliffe, Ph.D., Guilio D’Angio, M.D.’ 1 Hospital of the University of Pennsylvania Department of Radiation Oncology, Phila., PA 2The Children’s Seashore House, Children’s Hospital of Philadelphia, Phila., PA
Purpose: To determine the significance of post-operative neurocognitive deterioration in children with medulloblastoma treated or without chemotherapy.
factors on subsequent with radiation therapy
with
The medical charts of 28 children who have undergone prospective Materials and Methods: and serial neurocognitive testing were reviewed. All children received radiotherapy with/without chemotherapy for non-metastatic medulloblastoma and are disease-free for intervals between 1.2 and 6 years. The mean and median age at diagnosis were respectively 6.9 and 6.8 years (range 1.5 16.5 years). The mean and median followup were respectively 3.5 and 3 years (range: l-6 years). The clinical courses of the patients were then correlated with the absolute and change in the quotients (FSIQ) of each child before and after radiation therapy. respective full scale intelligence Eight of the 28 children had post-operative cranial nerve deficits or Results: hemiparesis, 6 had meningitis, 5 had subdural hematomas requiring evacuation, and 9 required multiple cranial procedures for shunt revision, emergent shunt placement, or scar excision. Of the subset of children with one or more of these factors, 13/1E (81%) sustained decreases in full-scale IQ (FSIQ) > 5 points, and 6 (37.5%) of Z- 20 points. By contrast, only 3/12 (25 %) of children without any of the above post-operative complications sustained FSIQ decreases > 5 points. This difference was significant (p = 0.01 via chi-square analysis).
Conclusions:
,
TiME IY..‘.,
Post-operative events or complications may account for some of the neurocognitive deterioration seen in these children after treatment. The occurrence of these factors is associated with significantly greater risk of neurocognitive deterioration. In these children, early detection and remedial intervention may be warranted. Furthermore, studies of the neurocognitive effects of treatment for children with medulloblastoma should include analysis of these post-operative factors.