Wilm's tumor: analysis of reduced dose radiotherapy in stage iii abdominal disease with favorable histology

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).

Proceedings

117

of the 31st Annual ASTRO Meeting

Prognostic factors were analyzed for patients with FH. In addition to stage, DFS was adversely affected by age. 100% 2 yr DFS was noted in 13 children under age 3 compared with 78% 2 yr DFS in 39 children over age 3 (p - .05). No adverse survival effect or increased risk of abdominal failure was evident in stage IIIIV patients with positive lymph nodes, operative spill, positive margins or gross disease residual following chemotherapy and 12 Gy. DFS was not affected by delay in initiating radiotherapy up to 5 weeks post-surgery. Abdominal disease control and overall survival are excellent with reduced dose abdominal radiotherapy (12 Gy) for FH stage III and IV Wilms' tumors in conjunction with present surgical techniques and chemotherapy.

5 GONADALSTA~S‘USDREPRODUCTIVEC~AClTYFOLLOWINGTREATMENTFORHODGKIN'SDlSEASEINCHILDHOOD-THESTANFORD EXPERIENCE T.T.SyOrtin, M.D.*, S.S.Donaldson, M.D.

*Anna Hamann Scholar, ASTRO, 1988-1989

Department of Radiation Oncology, Stanford University Medical Center, Stanford, California, 94305 Whereas gonadal toxicity among adults lreated for Hodgkin’s disease has been described, the degree of gonadal injury in children has not yet been defined. We reviewed the experience at Stanford University Medical Center during the years 1965-1986 to ascertain the impact of therapy. There were 240 patients @ts.)$ age 15 (range 2-15, median 13), of whom there were 92 girls and 148 boys. The median followup was 9 years, with maximum followup of 26 years. Of these patients, data on gonadal function were available on 19 boys, 3 of whom were prepubertal (no clinical evidence of sexual maturation and/or age ~13). Their evaluation included semen analysis (14 pts.), testicular biopsy (I pt.) or the ability Loprocreate (3pts.). Serum gonadotmpic hormone levels (FSH, LH) were studied among 10 boys with abnormal sperm counts. Data on menstrual history, pregnancy and offspring were available on 86 (92%) of the girls. BOYS TREATMENT

PELVIS(GY) 40.45

Radiation(XRT)

none +I-

MOP(P)+ $MINIMuM Ol6CYCLE

GIRLS TREATMENT Radiation(XRT)

# 3

TEST Semen analysis

RESULTS 3 oligospermia (< 1 mi./ml.)

1 3 1 11

testicularbiopsy

atrophy 3 fatheredchildren fathereda chid 9 azoospennia (no spermseen) 1 oligospermia (< 1 miJm1.) 1 normal ct. (267 mi./ml.)

semen analysis

YRS.POSTTREATMENT IO-11 1 9.19 3 l-11 4 12

PELVIS(GY) OOPHOROPEXY # #OVARIAN FAILURE # PREGNANT #PREGNANCY #CHILDREN #ABORTION + 40-44 9 1 3 6 2 3 1 40-44 1

MOP(P)+ $rnlN!hwM oi 6CYcLEs

MOPP/ABVD;otber** **P*“c,VB.~PBYD~S

none 40-44 40-44 20-35 20-35 none +i-

24 7 1 4 2 17 21

+ +

0 4 1 1 2 1 0

11 1

21 1

16 1

6 2

9 2

7 1

4

1

Inboys, sexual maturation was attained without need for androgen replacement. Semen analysis in 10 of 11 azoospermic boys treated with MOP(P)x6? pelvicXRT, show no evidence of recovery of spermatogenesis with10 years followup. 4 azoospermic boys (3 with pelvic XRT alone, 1 with pelvic XRT+MOP(P)x6) had associated hydrocoele following treatment. There is no strict correlation between sterility and serum gonadotropin levels. 75 of the 86 girls (87%)have normal menstrual function. None of the females with pelvic XRT without oophoropexy have been able to maintain ovarian function. In summary, both the prep&&al and pubertal testes are affected by MOP(P)x6 *pelvic XRT. With MOP(P)_pelvic XRT, ovarian injury is directly related to both the # of cycles of chemotherapy and dose of pelvic XRT. Chances of maintaining gonadal function are significantly greater among girls than boys following combined modality treatment. The progeny of patients treated for Hodgkin’s disease during childhood appear normal and no excess fetal wastage has been noEd.

6 ADVERSE SEQUCLAE OF CY’TO7’OXTC THERAPY IX LCKG ‘TEFJI SURVIVORS Cillciy

Sclwartz,

Louis

Constine,

Wendy

L.

OT- PlIDIATRIC

EIALlGNAXCY

Hohbie,

An awareness of tlie adverse seq~~elaf IfollowiIl:: cytotoxic therapy for children is essentinl to diagnose these effects, determine preventative and corrective actions and modify therapy to minimize late effects. IJe have evaluated 84 patients ( 5 years from diagnosis, >‘3 vrs disease free) in R clinic focused solely on th i s prob 1em. The disease breakdown was leukemia 37%, Wilms’ tumur (WI’) 15%, Hodgkins’ disease (HD) 1 I%, Sil rcoma 1 _ri:, brain turn(Jr (HT) 5%, non-Hodgkins’ lymphoma (NHT,) 5%, histiocytosis 3.5X, others (‘3.5Z). Stwcnt?‘-four pts (88%) ) including 58/70 (83%) treated with irradiation (RT), had at least c,ne adverse effect