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Results of radiation therapy for retinoblastoma in children less than one year old
Proceedings of the 31st Annual ASTRO Meeting
ABSTRACTS
OF ASTRO
SCIENTIFIC
NASOPHARYNGEAL CARCINOMA IN THE YOUNG - A COMBINED
PAPERS
M.D. ANDERSON
TO BE PRESENTED
AND STANFORD
;Leslye Ingersoll, M.DI; IShiao Y. Woo, M.D.; *?arah S. Donaldson, II. D . Moshe H. Maor, M.D.; Mary Jane Oswald, B.S.; Lester J. Peters, M.D. 1
UT M.D. Anderson
Cancer
Center,
Houston,
Texas;
2
Stanford
University
115
EXPERIENCE
; IJohn G. Giesler, M.D.;
Medical
Center,
Stanford,
California
Between 1956 and 1988, 42 children and adolescents (age 4-21 years) with a diagnosis of nasopharyngeal carcinoma were treated at M.D. Anderson Cancer Center, and 15 patients (pts) were treated at Stanford University Medical Center. The male to female ratio was 2:l. Forty-five pts had lymphoepithelioma, 11 had squamous cell carcinoma, and 1 had unclassified carcinoma. The stage distribution was as follows: Stage I 2, stage II 3, stage III 3, stage IV 49. All patients were treated with primary radiotherapy (XRT) and 14 oatients had chemotherapy (CT) in addition to XRT, with different combinations of the following drugs: vincristine, bleomycin, cytoxan, cisplatinum, 5 FU, methothrexate, adriamycin, actinomycin D. The total dose of XRT to the primary ranged from 45 Gy to 86.7 Gy (median 64.5 Gy) including the boost given either by external beam or intracavitary insertion (with irridium 192, cesium 137, or iodine 131). The upper necks were commonly included in the primary XRT fields, while the clinically uninvolved lower necks received 45-50 Gy. Twenty-six patients are alive 6 months to 178 months (median 93 months) from diagnosis. The 5 and 19 year actuarial survival are respectively 51% and 36%, and the 5 and 10 year freedom from relapse are both 51%. There were no recurrences after 42 months. Three patients died of unrelated causes without evidence of disease. The pattern of failure was as follows: distant metastasis only 21, loco-regional only 1, both 5. The most common sites of distant metastasis were bones, lungs, and liver. Although there were trends suggesting that (1) females fared better than males, (2) patients with N2 or N3 disease or lymphoepithelioma had a worse outcome than those who had NO or Nl disease or squamous cell carcinoma, (3) patients who received 65 Gy or more to the primary had a better outcome than those who received less than 65 Gy, (4) patients who received chemotherapy fared better than those who did not, none of the differences achieved statistical significance at p=O.O5. Chronic morbidities included dry mouth 16, soft tissue fibrosis or trismus 15, chronic otitis 5, pituitary dysfunction 3, hypothyroidism 5, and second neoplasm 2 (one within XRT field). In conclusion, (1) nasopharyngeal carcinoma in children and adolescents most commonly presents as advanced loco-regional disease, (2) the outcome of treatment does not seem to be different from that in older adults, (3) high dose XRT secures loco-regional control in the great majority of ots although there are significant treatment-related morbidities, (4) distant metastasis is the major reason for treatment failure and an effective systemic therapy needs to be developed. However, based on results in the literature as well as the experience in this report, the impact of currently available chemotherapeutic agents on disease control is unclear, and a randomized trial in a cooperative group setting will be needed to prove or refute the value of chemotherapy.
2 EUZSULTSOF
RADIATION THERAPY FOR RETINOBIASTOMA IN CHILDREN LESS THAN ONE TEAR OLD
Fontanesi, .I,Kun, LE, Pratt, C, Meyer, D, Hustu, HO, Pao, WJ, Brooks, L Departments of Radiation Oncology and Hematology/Oncology,St. Jude Children's Research Hospital, Memphis, TN, and Vitreoretinal Foundation, Memphis, TN Twenty-eight children who were less than one year old at the time of diagnosis of retinoblastoma (RB) were treated between 1963 and 1985. Bilateral RB was noted in 23 patients with 20 receiving irradiation to only a single eye and 3 patients being treated to both eyes. Five patients underwent irradiation following diagnosis of unilateral RB. All cases were staged utilizing both the Reese-Ellsworth (R-E) and the St. Jude Children's Research Hospital system (SJ). The R-E groups were as follows: Group I and II - 15; Group III 9; Group IV - 0; Group V - 7. There were 28 SJ stage I and 3 stage II lesions. Irradiationwas deliveredutilizing a single anterior field (23 eyes) or utilizing lens-sparing techniques with a lateral single port or a combination lateral field with lens-sparing anterior blocking. Total doses ranged between 22.5 and 43.6 Gy utilizing 150 to 180 cGy/fraction (n - 24) and 180 - 225 cGy/fraction (n - 7). Followup has ranged from 36 to 256 months (median 90). Twenty-seven of 28 (96%) children have survived from 60 to 256 months following diagnosis (median 99). Ocular survival is noted in 26/28 patients. Primary ocular control by stage and total dose are as follows: R-E STAGE I-II III V
1' 12/15 3/9 6/7
<36 Gy 7/8 2/5 4/5
>36 5/7 l/4 2/2
Median time to failure following irradiation was 10 months (range 3 to 53 months). Ten eyes required post-irradiation cryotherapy with 3 of these eventually undergoing re-irradiation utilizing either external beam or episcleral plaque. Ocular preservation was noted in 8 eyes with enucleation necessary in 2 (a single
Radiation
116
Oncology,
Biology,
Physics
October
1989, Volume
17, Supplement
1
patient for recurrent massive RB and a second patient requiring enucleation following unsuccessful repair of retinal hemorrhage). At last followup, 26 patients demonstrated ocular viability with visual acuity of 20/70 or better with Cataract formation was noted in 21/23 patients following anterior fields with no patient correction in 17. One child has treated utilizing lens-sparing techniques having evidence of posterior subscapular cataract. developed a second malignancy, an osteosarcoma of the nasopharyngeal cavity. Based on the data which is presented, there is no evidence that a dose response curve exists for this patientpopulationwith the techniques utilized. Although most children develop posterior subscapular cataracts At present, although when treated with anterior fields, there has been no complication from their removal. each child is individualized, for early stage lesions a dose not exceeding 36 Gy appears to be adequate.
3 LONG TERM THERAPY T.J. Kinsella’,
FOLLOW-UP
J. Miser’,
OF
B. Waller’,
Radiation Oncology’ and Pediatric Institute, Bethesda, MD 20892
EWING’S
SARCOMA
D. Venzon’, Oncology*
PATIENTS
E. Glatstein’,
Branches
L. Weaver*
and Biostatistics
TREATED
WITH
COMBINED
MODALITY
and M. Horowitz’ and Data Management
Sectiot?,
National
Cancer
Ewing’s sarcoma is the second most common malignant bone tumor in adolescents and young adults. Local treatment alone results in an uncommon (3-5 yrs) is seldom reported. Between 1968 and 1980, 107 patients with Ewing’s sarcoma were treated on sequential combined modality protocols (S, - 14 pts; S, - 19 pts; S, - 74 pts) at the National Cancer Institute. These protocols involved combination chemotherapy (S, - CTX, VCR; S, - CTX, VCR, ACTINO-D; S, - CTX, VCR, ADR) and Iocal irradiation to the 1’ lesion (50 Gy). NO surgical resection was planned as part of the protocols, although 16 pts had surgery prior to referral and 2 pts were felt to have a complete resection. 86 pts presented with localized disease and 21 pts presented with metastases (11 pts with multiple metastatic sites). The 1 o lesion involved the central skeleton in 41 pts and an extremity in 66 pts. With a median potential follow-up of ~15 yrs, 28 pts (27%) remain alive while 7.5 pts died and 4 pts were lost to follow-up. For the entire group of patients, disease free (DFS) and overall survival (OS) decreased most rapidly during the initial 5 years of follow-up with 5 yr-DFS of 29% and 5 yr-OS of 39%. Patients presenting with localized disease showed a significantly improved DFS and OS at 2, 5, 10 and 15 yrs (DFS - 52%, 37%, 35%, 33%; OS - 68%, 51%, 39%, 34% respectively) compared to patients presenting with metastases where only 2 pts are long term survivors (>5 yrs). 11 pts relapsed within the XRT field as the first site of failure while the vast majority of systemic failures occurred initially in lung and other bones. The % local control within the XRT field at 2, 5, 10 and 15 yrs of follow-up were 92%, 82%, 79% and 79% respectively. We conclude that the majority (1 75%) of patients with Ewing’s sarcoma relapsed within 5 yrs of these combined modality therapies, although late relapse (5-15 yrs) did occur. Local failure occured in 20% of patients within the first 5 yrs of follow-up. While more intensive combined modality regimens have been reported to improve the % complete response (~90%) and 2 yrs DFS (60-70%), longer follow-up of these recent studies is necessary to measure any effect on improved cure rates in Ewing’s sarcoma.
4 WILM'S
TUMOR:
ANALYSIS
OF REDUCED
DOSE RADIOTHERAPY
IN STAGE III ABDOMINAL
Robert L. Tobin, James Fontanesi, Larry E. Kun, Diane L. Fairclough, Douglass, Judith Wilimas, Mahesh A. P. Kumar, Jesse J. Jenkins Department of Radiation Oncology, Biostatistics, Memphis, TN
DISEASE
H. Omar Hustu,
Oncology, Thomas Jefferson University, Philadelphia, Surgery and Pathology, St. Jude Hematology/Oncology,
WITH FAVORABLE William
HISTOLOGY
J. Pao, Edwin C.
PA; Departments of Radiation Children's Research Hospital,
Treatment outcome for sixty three children with Wilms' tumor who received abdominal radiotherapy are reviewed. All patients were treated between 1979-88 as part of a prospective protocol study of Wilms' tumor. Patients were treated according to histology and operative stage. The review includes all patients with NWTS Stage III disease and all Stage IV cases with similar abdominal disease extent. All patients received triple agent chemotherapy which consisted of dactinomycin, vincristine, and doxirubicin. Patients with favorable histology (FH) received a uniform dose of 12 Gy to the whole abdomen or hemi-abdomen at 150 cGy/day; patients with unfavorable histology (UH) received 12 to 36 Gy. Chemotherapy was started within one week from surgery, and radiotherapy was instituted 2-5 weeks post surgery. The 2 year disease-free survival (DFS) was calculated by stage. Fifty two patients (83%) had favorable histology (i.e. without anaplastic or sarcomatous changes). In this group 2 yr DFS rates for stage III and IV patients were 90% and 71%, respectively. Intraabdominal relapse occurred in 3/52 (6%) patients. Eleven patients (1%) were found to have unfavorable histology (UH). The 2 yr DFS was 80% for the stage III patients and 20% for stage IV patients with UH. Abdominal relapse occurred in 3/11 (p - .OOOl).
ABSTRACTS
OF ASTRO
SCIENTIFIC
NASOPHARYNGEAL CARCINOMA IN THE YOUNG - A COMBINED
PAPERS
M.D. ANDERSON
TO BE PRESENTED
AND STANFORD
;Leslye Ingersoll, M.DI; IShiao Y. Woo, M.D.; *?arah S. Donaldson, II. D . Moshe H. Maor, M.D.; Mary Jane Oswald, B.S.; Lester J. Peters, M.D. 1
UT M.D. Anderson
Cancer
Center,
Houston,
Texas;
2
Stanford
University
115
EXPERIENCE
; IJohn G. Giesler, M.D.;
Medical
Center,
Stanford,
California
Between 1956 and 1988, 42 children and adolescents (age 4-21 years) with a diagnosis of nasopharyngeal carcinoma were treated at M.D. Anderson Cancer Center, and 15 patients (pts) were treated at Stanford University Medical Center. The male to female ratio was 2:l. Forty-five pts had lymphoepithelioma, 11 had squamous cell carcinoma, and 1 had unclassified carcinoma. The stage distribution was as follows: Stage I 2, stage II 3, stage III 3, stage IV 49. All patients were treated with primary radiotherapy (XRT) and 14 oatients had chemotherapy (CT) in addition to XRT, with different combinations of the following drugs: vincristine, bleomycin, cytoxan, cisplatinum, 5 FU, methothrexate, adriamycin, actinomycin D. The total dose of XRT to the primary ranged from 45 Gy to 86.7 Gy (median 64.5 Gy) including the boost given either by external beam or intracavitary insertion (with irridium 192, cesium 137, or iodine 131). The upper necks were commonly included in the primary XRT fields, while the clinically uninvolved lower necks received 45-50 Gy. Twenty-six patients are alive 6 months to 178 months (median 93 months) from diagnosis. The 5 and 19 year actuarial survival are respectively 51% and 36%, and the 5 and 10 year freedom from relapse are both 51%. There were no recurrences after 42 months. Three patients died of unrelated causes without evidence of disease. The pattern of failure was as follows: distant metastasis only 21, loco-regional only 1, both 5. The most common sites of distant metastasis were bones, lungs, and liver. Although there were trends suggesting that (1) females fared better than males, (2) patients with N2 or N3 disease or lymphoepithelioma had a worse outcome than those who had NO or Nl disease or squamous cell carcinoma, (3) patients who received 65 Gy or more to the primary had a better outcome than those who received less than 65 Gy, (4) patients who received chemotherapy fared better than those who did not, none of the differences achieved statistical significance at p=O.O5. Chronic morbidities included dry mouth 16, soft tissue fibrosis or trismus 15, chronic otitis 5, pituitary dysfunction 3, hypothyroidism 5, and second neoplasm 2 (one within XRT field). In conclusion, (1) nasopharyngeal carcinoma in children and adolescents most commonly presents as advanced loco-regional disease, (2) the outcome of treatment does not seem to be different from that in older adults, (3) high dose XRT secures loco-regional control in the great majority of ots although there are significant treatment-related morbidities, (4) distant metastasis is the major reason for treatment failure and an effective systemic therapy needs to be developed. However, based on results in the literature as well as the experience in this report, the impact of currently available chemotherapeutic agents on disease control is unclear, and a randomized trial in a cooperative group setting will be needed to prove or refute the value of chemotherapy.
2 EUZSULTSOF
RADIATION THERAPY FOR RETINOBIASTOMA IN CHILDREN LESS THAN ONE TEAR OLD
Fontanesi, .I,Kun, LE, Pratt, C, Meyer, D, Hustu, HO, Pao, WJ, Brooks, L Departments of Radiation Oncology and Hematology/Oncology,St. Jude Children's Research Hospital, Memphis, TN, and Vitreoretinal Foundation, Memphis, TN Twenty-eight children who were less than one year old at the time of diagnosis of retinoblastoma (RB) were treated between 1963 and 1985. Bilateral RB was noted in 23 patients with 20 receiving irradiation to only a single eye and 3 patients being treated to both eyes. Five patients underwent irradiation following diagnosis of unilateral RB. All cases were staged utilizing both the Reese-Ellsworth (R-E) and the St. Jude Children's Research Hospital system (SJ). The R-E groups were as follows: Group I and II - 15; Group III 9; Group IV - 0; Group V - 7. There were 28 SJ stage I and 3 stage II lesions. Irradiationwas deliveredutilizing a single anterior field (23 eyes) or utilizing lens-sparing techniques with a lateral single port or a combination lateral field with lens-sparing anterior blocking. Total doses ranged between 22.5 and 43.6 Gy utilizing 150 to 180 cGy/fraction (n - 24) and 180 - 225 cGy/fraction (n - 7). Followup has ranged from 36 to 256 months (median 90). Twenty-seven of 28 (96%) children have survived from 60 to 256 months following diagnosis (median 99). Ocular survival is noted in 26/28 patients. Primary ocular control by stage and total dose are as follows: R-E STAGE I-II III V
1' 12/15 3/9 6/7
<36 Gy 7/8 2/5 4/5
>36 5/7 l/4 2/2
Median time to failure following irradiation was 10 months (range 3 to 53 months). Ten eyes required post-irradiation cryotherapy with 3 of these eventually undergoing re-irradiation utilizing either external beam or episcleral plaque. Ocular preservation was noted in 8 eyes with enucleation necessary in 2 (a single
Radiation
116
Oncology,
Biology,
Physics
October
1989, Volume
17, Supplement
1
patient for recurrent massive RB and a second patient requiring enucleation following unsuccessful repair of retinal hemorrhage). At last followup, 26 patients demonstrated ocular viability with visual acuity of 20/70 or better with Cataract formation was noted in 21/23 patients following anterior fields with no patient correction in 17. One child has treated utilizing lens-sparing techniques having evidence of posterior subscapular cataract. developed a second malignancy, an osteosarcoma of the nasopharyngeal cavity. Based on the data which is presented, there is no evidence that a dose response curve exists for this patientpopulationwith the techniques utilized. Although most children develop posterior subscapular cataracts At present, although when treated with anterior fields, there has been no complication from their removal. each child is individualized, for early stage lesions a dose not exceeding 36 Gy appears to be adequate.
3 LONG TERM THERAPY T.J. Kinsella’,
FOLLOW-UP
J. Miser’,
OF
B. Waller’,
Radiation Oncology’ and Pediatric Institute, Bethesda, MD 20892
EWING’S
SARCOMA
D. Venzon’, Oncology*
PATIENTS
E. Glatstein’,
Branches
L. Weaver*
and Biostatistics
TREATED
WITH
COMBINED
MODALITY
and M. Horowitz’ and Data Management
Sectiot?,
National
Cancer
Ewing’s sarcoma is the second most common malignant bone tumor in adolescents and young adults. Local treatment alone results in an uncommon (
4 WILM'S
TUMOR:
ANALYSIS
OF REDUCED
DOSE RADIOTHERAPY
IN STAGE III ABDOMINAL
Robert L. Tobin, James Fontanesi, Larry E. Kun, Diane L. Fairclough, Douglass, Judith Wilimas, Mahesh A. P. Kumar, Jesse J. Jenkins Department of Radiation Oncology, Biostatistics, Memphis, TN
DISEASE
H. Omar Hustu,
Oncology, Thomas Jefferson University, Philadelphia, Surgery and Pathology, St. Jude Hematology/Oncology,
WITH FAVORABLE William
HISTOLOGY
J. Pao, Edwin C.
PA; Departments of Radiation Children's Research Hospital,
Treatment outcome for sixty three children with Wilms' tumor who received abdominal radiotherapy are reviewed. All patients were treated between 1979-88 as part of a prospective protocol study of Wilms' tumor. Patients were treated according to histology and operative stage. The review includes all patients with NWTS Stage III disease and all Stage IV cases with similar abdominal disease extent. All patients received triple agent chemotherapy which consisted of dactinomycin, vincristine, and doxirubicin. Patients with favorable histology (FH) received a uniform dose of 12 Gy to the whole abdomen or hemi-abdomen at 150 cGy/day; patients with unfavorable histology (UH) received 12 to 36 Gy. Chemotherapy was started within one week from surgery, and radiotherapy was instituted 2-5 weeks post surgery. The 2 year disease-free survival (DFS) was calculated by stage. Fifty two patients (83%) had favorable histology (i.e. without anaplastic or sarcomatous changes). In this group 2 yr DFS rates for stage III and IV patients were 90% and 71%, respectively. Intraabdominal relapse occurred in 3/52 (6%) patients. Eleven patients (1%) were found to have unfavorable histology (UH). The 2 yr DFS was 80% for the stage III patients and 20% for stage IV patients with UH. Abdominal relapse occurred in 3/11 (p - .OOOl).