Marilyn Sonley

Posterior fossa medulloblastoma in childhood: Treatment results and a proposal for a new staging system

Seventy-two children with posterior fossa medulloblastoma were diagnosed at the Hospital for Sick Children, Toronto, from 1977 to 1987 and treated by standard methods. The 5- and 10-year survival and disease-free survival rates were 71% and 63%, and 64% and 63%, respectively. Total tumor resection, as determined by the surgeon was the most significant favorable prognostic factor. Post-operative meningitis, a residual enhancing mass lesion on the post-operative, pre irradiation CT scan and dissemination to the brain or cord at diagnosis were unfavorable factors. These four easily definable factors were used to define a staging system with prognostic significance. Five-year disease-free survival rates were for Stage I (total resection, no adverse factor) 100%, Stage II (total resection with one or more adverse factor or less than total resection with no other adverse factor) 78%, and Stage III (less than total resection with one or more adverse factor) 18%. Evaluation of treatment results in medulloblastoma requires that these prognostic factors be known.

Pineal region germinomas in childhood treatment considerations

From 1967-1986, 21 children were treated for pineal germinoma, including 16 biopsy-proven, 2 biopsy non-diagnostic, and 3 metastatic unbiopsied (marker negative) patients. Ten of 18 (56%) biopsied patients underwent partial or sub-total tumor resection. Twenty patients were irradiated, 19 of whom are alive. No irradiated patient died of progressive germinoma, but two patients relapsed in the spinal cord and required treatment intensification for salvage. Long-term survivors have significant morbidity. Determination of the minimum effective treatment remains the chief therapeutic challenge.

Echocardiography in adriamycin cardiotoxicity

Twenty‐six patients receiving adriamycin for osteogenic sarcoma had serial echocardiographic assessments of their left ventricular function. A statistically significant deterioration of function was noted throughout the course. Ventricular function tended to normalize in the period following cessation of adriamycin. The velocity of circumferential fibre shortening (Vcf) and ejection fraction (EF) were the best parameters. Sudden declines in these values resulted in us withholding therapy until the parameters again improved. Fatal congestive heart failure was seen in only one patient. Echocardiography thus provides the clinician with a valuable tool enabling one to improve the therapeutic usefulness of adriamycin by removing much of the uncertainty over the development of cardiotoxicity.

Hodgkin's disease in children. A retrospective analysis: 1958-73

One hundred nine children with Hodgkins disease consecutively treated at The Princess Margaret Hospital, Toronto, during 1958–1973 are reviewed. Crude 5‐year survival rates, regardless of stage, were 1958–64–50%: 1965‐68–73%; and 1969–73–95%. The corresponding 5‐year relapse‐free rates were 19%, 20%, and 57%. This progressive improvement in results was associated with the sequential introduction of lymphography and laparotomy with splenectomy, the change from involved field to extended field irradiation, and the introduction of multiple agent chemotherapy, at first for generalized relapse and recently as elective initial therapy, combined with extended field irradiation for children in advanced stages.

Soft-tissue sarcomas in the young. Medical treatment advances in perspective

One hundred and sixty‐two patients with all types of soft tissue sarcoma, less than 21 years old and diagnosed at a single institution during the period 1958 through 1976, were studied. The major histologic subset comprised 115 patients with either embryonal rhabdomyosarcoma or undifferentiated sarcoma. In this group, responses of patients with stage I‐II disease to local treatment alone indicated that at least half had no occult metastatic disease. Responses to irradiation alone in stage III disease indicated that only about a quarter of these patients had no occult disease. Sustained local control at the primary site by irradiation was observed in 68% of the patients given doses of 4500 rad or greater compared with 22% at lower doses. The effectiveness of adjuvant chemotherapy was best seen in patients with stage III disease as a decrease in relapse rate and a lengthening of the time to first relapse. In these patients it appeared that occult metastatic disease could be eradicated in approximately half of the patients affected.

Additive therapy in the maintenance of remission in acute lymphoblastic leukemia of childhood: the effect of the initial leukocyte count.

Following introduction of M1 marrow remission in 81% or 329 of 407 patients treated with prednisone and biweekly intravenous methotrexate, 321 patients were randomly assigned to one of six maintenance treatment regimens designed to evaluate the effect of bimonthly intravenous pulses of the additives actinomycin D, nitrogen mustard, and 5‐fluorouracil on the duration of remission in acute lymphoblastic leukemia of childhood. In patients with an initial WBC below 20,000/mm3, a statistically significant beneficial effect of additives was observed in Regimen 1 (actinomycin D with 6MP, nitrogen mustard with methotrexate), Regimen 2 (actinomycin D with 6MP and methotrexate), and Regimen 6 (5‐fluorouracil with 6MP and methotrexate). Children with an initial WBC above 20,000/mm3 had the least favorable prognosis; in this group additives appeared to have an adverse effect but the difference was not significant. Survival was also significantly longer in patients with an initial WBC of less than 5000/mm3, when compared to those with an initial WBC of above 20,000/mm3. Little difference in the degree or frequency of hematologic, gastrointestinal, and hepatic toxicity was encountered in the various regimens. These results indicate that additive therapy is beneficial in those patients with the most favorable prognosis and that the prognostic effects of the initial WBC must be given careful consideration in future protocol design, patient randomization, and data analysis of controlled clinical trials.

Hodgkin's disease in children: treatment with low dose radiation and MOPP without staging laparotomy: a preliminary report.

Twenty‐seven children with previously untreated Hodgkins disease (CS I‐2, II‐13, III‐3, IV‐9) were given three cycles of MOPP to induce a remission which was consolidated with extended field radiation (2000‐3500 rad) and three cycles of MOPP. Surgical staging was discontinued. Twenty‐five of 27 children have not relapsed (range 15 + ‐64+ months; median 39+ months); two children have died, one of uncontrolled Hodgkins disease and one of acute infection while in complete remission. Actuarial 3 and 5 year survival rates and relapse‐free rates are 91%. The merits of this treatment approach are discussed.

Ewing's Sarcoma Adjuvant total body irradiation, cyclophosphamide and vincristine

Abstract For patients with Ewings Sarcoma treated from 1960 to 1973, the 5-year survival and relapse free rates were: primary site irradiation without systemic treatment (16 patients) 25% and 12%: primary site irradiation with total body irradiation (13 patients) 38% and 23%. The 4-year survival and relapse free rates for 12 patients treated from 1970 to 1973 by primary site irradiation, total body irradiation and one year of elective Cyclophosphamide and Vincristine were 40% and 30%. These data provide further evidence that systemic therapy may be effective in eradicating occult metastases in a moderate proportion of patients with Ewings Sarcoma.

Ewing's sarcoma: a trial of adjuvant chemotherapy and sequential half-body irradiation

The results of a pilot study using adjuvant chemotherapy and sequential half-body irradiation (HBI) for nonmetastatic Ewings sarcoma are presented. Seventeen patients received Cyclophosphamide, Vincristine, and Adriamycin (8 cycles), followed by sequential radiation treatment of the upper (500 cGy) and lower (600 cGy) half body. Survival at 3 years was 49%. These results are contrasted with those for 18 concurrently treated patients who received standard adjuvant therapy. Overall 5-year survival and relapse-free survival for these 35 consecutive patients was 61 and 53%. The pilot protocol was given on an out-patient basis with limited and acceptable acute toxicology. Further study is necessary to determine the value of the pilot protocol.