Demetrius Traggis

Adjuvant Methotrexate and Citrovorum-Factor Treatment of Osteogenic Sarcoma

Abstract Twenty consecutive patients with osteogenic sarcoma without visible metastases received adjuvant chemotherapy starting three weeks after local treatment of the primary tumor with operation or radiation. Adjuvant chemotherapy consisted of intravenous vincristine followed in 30 minutes by a six-hour infusion of methotrexate. Two hours later citrovorum factor was administered every six hours for 12 doses. Such treatment courses were given at three-week intervals. Ninety-eight patients referred to this center between 1950 and June, 1972, served as controls. The incidence of pulmonary metastases was significantly reduced by adjuvant chemotherapy to two as opposed to the expected 12.2 cases. Nineteen of the 20 patients treated with the adjuvant chemotherapy are surviving with follow-up periods of two to 23 months. Only six of 212 courses of treatment were associated with myelosuppression or stomatitis. These observations indicate that systemic (adjuvant) chemotherapy delays relapse and may provide defi...

Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy.

Vincristine, actinomycin D, and cyclophosphamide (VAC) were administered to 14 patients with Ewings sarcoma. The primary tumors were treated with radiation therapy and concurrent chemotherapy. Nine patients had no visible metastases at diagnosis: two died following the development of pulmonary metastases and the rest have been free of disease for periods varying from 4 months to 4 1/2 years following completion of treatment. This contrasts with a 27% survival in patients previously treated at this center with single agent chemotherapy. Five other patients had demonstrable metastases at diagnosis: VAC chemotherapy achieved complete regression of pulmonary metastases in three for 9, 9+ and 24+ months, respectively. Following disappearance of tumor in the latter two, pulmonary irradiation was administered in an attempt to consolidate the response, but tumor recurred 6 months later. These patients eventually died of widespread disease although survival appeared prolonged in comparison to that seen in past experience. Chemotherapy was well tolerated, although three patients developed hemorrhagic cystitis, necessitating discontinuation of cyclophosphamide. The data suggest the potential for prolonged control and an increase in the cure rate with this therapeutic approach.

Favorable outlook for children with mediastinal neuroblastoma

Abstract Twenty-seven infants and children between the ages of 2 wk and 8 yr have been treated for mediastinal neuroblastoma, and 23 are alive, 20 more than 2 yr. Fourteen patients were under 1 yr of age, and eight were over 3 yr at diagnosis. Tumor was limited to the mediastinum in 11 children but had metastasized in 16 children to cervical nodes (10), bones (5), and epidural space (3). The primary tumor was completely excised in eight and incompletely in 16. The mass was not removed in three patients. Radiotherapy (1000–4200 R) was administered to 25 patients. Chemotherapy, usually with nitrogen mustard and long-term cyclophosphamide, was employed in 23. The four deaths occurred in children over 212 yr of age, all of whom had widespread tumor in bones at diagnosis, and in three the primary tumor was never excised. A large primary tumor, lymph node or epidural metastases, Horners syndrome, erosion of ribs and thoracic vertebrae, and incomplete surgical excision did not adversely affect the prognosis.

Rhabdomyosarcoma in children: Improved outlook with a multidisciplinary approach☆☆☆

Rhabdomyosarcoma has received increasing recognition as a major soft tissue tumor in children. In 1946 Stout [I] collected 121 cases, twenty-five of which involved children. In 1950 Stobbe and Dargeon [2] drew attention to embryonal rhabdomyosarcoma of the head and neck in children. More recently, Sutow et al [3] suggested that rhabdomyosarcoma occurs at least as frequently as neuroblastoma and Wilms’ tumor. Mahour et al [4] noted that it was the most common sarcoma of the somatic soft tissues in children, whereas Enzinger and Shiraki [5] indicated that alveolar and embryonal rhabdomyosarcomas were the two most frequent soft tissue tumors affecting patients less than twenty years of age. Sixtyone patients with rhabdomyosarcoma were treated at the Children’s Cancer Research Foundation in Boston, Massachusetts from 1947, when the Foundation was established, to 1969. This number represents 2 per cent of the 3,304 patients with various forms of cancer and 5 per cent of the 1,301 patients with malignant solid tumors seen during this period.

WEEKLY HIGH-DOSE METHOTREXATE-CITROVORUM FACTOR IN OSTEOGENIC SARCOMA Pre-Surgical Treatment of Primary Tumor and of Overt Pulmonary Metastases

Vincristine‐high‐dose methotrexate‐citrovorum factor (VCR‐MTX‐CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR‐MTX‐CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR‐MTX‐CF. Among the eight patients who had not received prior VCR‐MTX‐CF, complete responses were obtained in three with primary tumors (this was followed by surigical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR‐MTX‐CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri‐weekly schedule utilized in previous studies.

The role of irradiation in central nervous system treatment and prophylaxis for acute lymphoblastic leukemia

The results of central nervous system (CNS) treatment with craniocervical irradiation and intrathecal methotrexate in 117 children with ALL achieved at the Joint Center for Radiation Therapy, The Childrens Hospital Medical Center, and The Sidney Farber Cancer Center are presented. A classification related to meningeal disease which correlates with prognosis is presented and the patients are analyzed within these groups. Of 80 patients classified in the most favorable groups (I and II), no child has suffered primary CNS relapse. Of the remaining 37 patients in less favorable groups (III, IV, and V), eight patients have experienced CNS relapse, five following or in conjunction with bone marrow relapse. The technical features of irradiation are reviewed and related to success of the treatment.

Prognosis for children with neuroblastoma presenting with paralysis

Since 1947, we have treated 19 children with neuroblastoma whose first symptoms were paralysis or weakness of an extremity, and/or incontinence due to tumor in the spinal canal. In 18 patients, the spine tumor was part of a dumbbell tumor which was present in the adjacent paravertebral area and in one, no extraspinal tumor was found. Aggressive treatment was employed for all. In 17 children, the intraspinal tumor was treated by laminectomy and irradiation with and without chemotherapy. Radiation and chemotherapy were used for two. The extraspinal tumor was excised totally in six and partially in six. All 12 children received postoperative radiation and chemotherapy. In 6 children, the extraspinal tumor was treated only with radiation and chemotherapy. Nine of 19 children are alive without evidence of neuroblastoma. Thirteen patients showed either partial (6) or full (7) neurologic recovery. Survival was related to the childs age at diagnosis and the extent of disease. While 8 of 9 children under 1 yr of age survived, only 1 of 10 children over 1 yr survived. None of the 5 children with Stage IV disease at diagnosis could be saved. The degree and frequency of neurologic recovery were greatest in children whose neurologic symptoms had been present the shortest times and were equal among those who survived and those who died. The outlook for children who became paralyzed by neuroblastoma is not hopeless; therapy aimed at saving life or neurologic function is both worthwhile and rewarding.

The role of radiation therapy in localized resectable intestinal non-Hodgkin's lymphoma in children.

Forty children with localized resectable intestinal non‐Hodgkins lymphoma were seen between 1948 and 1974. Survival was related to the extent of disease at presentation and to therapy. No deaths occurred after 15 months and no recurrences occurred after 13 months after diagnosis. Six of eight stage IE patients (75%) and nine of 29 stage IIE patients (31%) have survived a minimum of 2 years; one of the three stage IVE patients has survived 17 years. Unfavorable prognostic findings at surgery were serosal involvement, presence of tumor at the surgical margins, mesenteric nodal involvement, and the presence of abdominal fluid or blood. Paraortic nodal involvement or multiple primary foci were universally fatal. Eight of 11 patients (73%) treated with surgery and whole abdominal irradiation (≥ 2000 rad) with or without chemotherapy have survived. Seven of 18 patients (39%) treated with surgery and low dose chemotherapy have survived. One of seven patients treated with surgery and localized or low dose radiation therapy with or without chemotherapy has survived. Four patients treated with surgery alone died. Bone marrow and central nervous system involvement occurred after previous disease relapse elsewhere.

Fluorine-18 bone scintigraphy in children with osteosarcoma or Ewing's sarcoma

Serial fluorine-18 bone scans and skeletal surveys were evaluated for usefulness in the staging of initial disease and for detection of metastases in children with osteosarcoma or Ewings sarcoma. Scintigraphy was more sensitive than skeletal surveys in the detection of bony metastases in both tumors, but was less sensitive than radiographs for the detection of pulmonary lesions. Bone metastases did not occur before pulmonary metastases in patients with osteosarcoma but did in patients with Ewings sarcoma. The effect of radiation therapy on the distribution of fluorine 18 throughout the bony skeleton is discussed.

Experience with clinical and operative staging of Hodgkin's disease in children☆

Accurate staging is critical for the proper treatment of Hodgkins disease. In the past 5 yr, 60 children with Hodgkins disease were staged by celiotomy which included splenectomy and biopsy of liver, retroperitoneal lymph nodes, and bone. Fifty children underwent staging celiotomy at initial diagnosis (Group I). Ten others were staged surgically because of suspected reactivation of disease diagnosed and treated before current staging methods were employed (Group II). Forty-one of 50 children in Group I had Stage I or II disease, seven Stage III, and two Stage IV. As a result of operation, therapy was altered in seven children. Three had a higher stag e and four a lower stage than that suspected by clinical evaluation, including two with liver involvement. Of the two patients in Group II, celiotomy revealed unsuspected splenic disease in seven, including one with liver involvement. Celiotomy and splenectomy were well tolerated and no long-term complications have been noted (average follow-up 2 yr). Forty-nine of 50 children in Group I and six of ten in Group II are alive without disease. No cases of sepsis attributable to splenectomy have been observed.