Philip R. Exelby

Non‐Hodgkin's lymphoma in children. A comparative study of two modalities of therapy

Eighty‐six children with non‐Hodgkins lymphoma were studied from 1964 to January 31, 1975. Seventy‐six percent of the 43 patients in the nonprotocol group had far advanced disease, and 76% had Rappaports diffuse histology. Only 11% of these patients survived free of disease. The second group of 43 patients received the LSA2L2 protocol. Seventy‐six percent had advanced disease and 86% diffuse histology. Of these patients 76% are surviving free of disease with a median observation time of 25+ months. Fifty‐one percent of the survivors are off therapy and without evidence of disease. Prognostic factors such as primary sites, stages, histology, and others are discussed. The most important prognostic factor is early and aggressive therapy, and the achievement of a complete response status within 1–2 months from onset of therapy.

Extracranial primitive neuroectodermal tumors. The memorial sloan‐kettering cancer center experience

The clinical data of 54 patients (57% males) with extracranial primitive neuroectodermal tumors (PNET) seen over a 20‐year period at Memorial Sloan‐Kettering Cancer Center were reviewed. The age at diagnosis ranged from 1 month to 81 years (median, 17 years). One PNET arose in a previously irradiated site. One patient had an unaffected identical twin. Primary sites were thoracopulmonary (n = 25), pelvis (n = 12), retroperitoneum or abdomen (n = 10), limbs (n = 5), neck (n = 1), and unknown (n = 1). At diagnosis, epidural extension was present in 13 patients with truncal primaries, and 11 patients had distant metastases. All of the latter died with disease. Progression‐free survival (PFS) among the 43 patients with localized tumors (all >5 cm) was 25% at 24 months. Two of 13 patients who relapsed after more than 12 months without therapy were long‐term survivors. Patients with localized PNET who had resection of all gross disease within 3 months of diagnosis had a significantly longer PFS (P = 0.0003). Radiation therapy caused tumor shrinkage but was not curative of measurable disease. A doseresponse effect was evident with the most commonly used drug, cyclophosphamide. Myeloablative regimens using melphalan (n = 8) or thiotepa (n = 1) with autologous bone marrow rescue were not clearly beneficial. The treatment results favor: (1) early surgical removal, (2) dose‐intensive use of drugs active against PNET (especially cyclophosphamide), and (3) radiation therapy to ablate residual microscopic disease.

Pediatric desmoid tumor : retrospective analysis of 63 cases

PURPOSE This study was conducted to evaluate clinical prognostic factors predictive of the probability of recurrence of desmoid tumor (DT). PATIENTS AND METHODS Sixty-three patients with histologically confirmed diagnosis of DT were retrospectively studied. Median age at diagnosis was 13 years. Patient distribution by site was as follows: 61% extremities, 18% head and neck, 13% trunk (including 5% intraabdominal), and 8% multicentric lesions. All patients had partial or complete resections; 20 patients also received radiotherapy and/or chemotherapy. RESULTS At a median follow-up time of 6 years since first treatment, the overall actuarial probability of having one or more recurrences was 75%. Age, sex, site, size, or number of previous recurrences had no significant impact on the likelihood of recurrence. The only factor associated with an increased proportion of recurrence-free patients was a negative margin of resection (70% v 15% with positive margins; P = .006). Of the four patients with more than 3 years follow-up since chemotherapy, two recurred, and of the 11 patients with the same follow-up after radiotherapy, four recurred, including two of five patients who received a dose of 50 Gy or more. No deaths directly related to tumor invasion were observed. CONCLUSION A surgical approach aiming at clear margins is presently the best treatment option. When this cannot be accomplished without severe disfigurement or function impairment, partial resection is an acceptable alternative, but one associated with a high risk of regrowth. Whether adjuvant strategies should be used in this situation remains to be addressed.

Multidisciplinary treatment of embryonal rhabdomyosarcoma in children

Twenty‐nine children under 15 years of age with embryonal rhabdomyosarcoma were treated according to a multidisciplinary protocol (T‐2). The protocol consisted of surgical removal of the tumor if possible, followed by chemotherapy, and also with radiation therapy in patients with gross or microscopic residual disease. Radiation therapy was given in the 4500–7000 rads range. The chemotherapy consisted of cycles of sequential administration of dactinomycin, Adriamycin, vincristine, and cyclophosphamide, with obligatory periods of rest. The drug therapy was continued for 2 years. Following surgery, clinicopathologic staging of the disease revealed 10 patients with no residual disease (I‐A), 5 with microscopic residual disease (I‐B), 5 with unresectable tumors (II), 6 with unresectable tumors plus regional lymph node involvement (III), and 3 with disseminated tumors (IV). Twenty‐four (82%) of the patients (20 Stages I‐II, 4 Stage III) are alive with no evidence of disease for 4+ to 42+ months. These results are superior to those achieved between 1960–1970 among 108 children treated at Memorial Sloan‐Kettering Cancer Center.

Non‐Hodgkin's lymphoma in children. A progress report on the original patients treated with the LSA2‐L2 protocol

This report is a follow‐up of the initial group of 39 children with non‐Hodgkins lymphoma treated with the LSA2‐L2 protocol as previously reported in Cancer (37:123–134, 1976). The disease‐free actuarial survival is 73%. All surviving patients are off therapy and have shown no evidence of recurrence with a median observation time of 70+ months. Their survival times range from 56+ to 88+ months from diagnosis. An analysis of successes and failures is discussed and modifications in the role of radiation therapy and surgery in the multidisciplinary management of children with non‐Hodgkins lymphoma are advocated. The results in the present series indicate that the LSA2‐L2 protocol has substantially improved the prognosis for children with non‐Hodgkins lymphoma. We have concluded that age, sex, primary site (perhaps with the exception of primary skeletal), and histology are not of prognostic significance. The amount of bulky widespread disease at initial presentation, early and aggressive therapy, and the achievement of a complete remission status within 1–2 months from onset of therapy are the most important prognostic factors.

Acute and late effects on normal tissues following combined chemo- and radiotherapy for childhood rhabdomyosarcoma and Ewing's sarcoma.

Twenty‐three patients with rhabdomyosarcoma and 15 patients with Ewings sarcoma, treated with radiation therapy to the local site and systemic multiagent chemotherapy are described. Acute reactions from combination chemotherapy and radiation therapy were noted in both groups of patients. These reactions often appeared after low doses of irradiation, required unplanned interruptions of treatments, and in some patients, led to discontinuation of radiation therapy. The chronic effects on normal tissues in both groups of patients have been severe in several cases.

Chemotherapy and thoractomy for metastatic osteogenic sarcoma. A model for adjuvant chemotherapy and the rationale for the timing of thoracic surgery

Forty‐five children with osteogenic sarcoma metastatic to the lung were treated with sequential chemotherapy, consisting of high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR), adriamycin, and cyclophosphamide, and the surgical removal of all pulmonary metastases when possible. Fourteen of the 45 patients had complete removal of all metastases at initial thoracotomy, followed by adjuvant chemotherapy. Ten of these 14 patients are surviving (all with no evidence of disease) for from 24–56 months (median 33+months) from the start of treatment. Thirty‐one of the 45 patients had diffuse pulmonary metastases and were treated with chemotherapy followed by multiple thoracotomies and further chemotherapy. Twelve of these 31 patients have no evidence of disease for from 6–41+ months (median 19+ months). The correlation of clinical response, with the surgical and histologic findings at the time of thoracotomy, following chemotherapy in this latter group of patients, has helped us to define the proper dose and scheduling of chemotherapy when used in an adjuvant situation. It also has provided a model for the efficacy of adjuvant chemotherapy in osteogenic sarcoma. In addition, this experience has led us to propose the following guidelines for the management of osteogenic sarcoma patients with pulmonary metastases: 1) pulmonary metastases large enough to be seen on roentgenogram should eventually be removed if possible, 2) patients with late occurring solitary pulmonary metastases should undergo initial surgical removal of pulmonary metastases, followed by “adjuvant” chemotherapy, and 3) patients with rapidly occurring or apparent multiple pulmonary metastases should undergo chemotherapy initially; if pulmonary metastases shrink in size or do not change in size over a period of 2–6 months of chemotherapy, an attempt should be made surgically to excise all “residual” disease prior to the continuation of chemotherapy. This approach to the treatment of osteogenic sarcoma in patients with pulmonary metastases has yielded an unexpectedly high disease‐free and prolonged survival rate, and demonstrates the value of aggressive treatment in this group of patients who classically had an extremely poor prognosis.

Combination therapy of urogenital embryonal rhabdomyosarcoma in children

Twenty‐seven children with embryonal rhabdomyosarcoma of the urogenital tract were treated between 1960‐1971. A review of their courses reveals that early stage of the disease at the time of diagnosis and multidisciplinary therapy —surgery, radiotherapy, and multiple drug therapy—offer the best chance for prolonged survival and cure. Seventeen (63%) of the 27 children are living and have been free of the tumor for 18 months‐10 years.

Prognostic factors and outcome in patients 21 years and under with colorectal carcinoma

This study aims to identify significant predictors of survival in pediatric and adolescent colorectal carcinoma. We retrospectively analyzed our experience with 29 histologically verified cases, of which 20 were resected for cure. Variables analyzed as predictors of survival included: (1) resectability, (2) regional nodal involvement, (3) depth of invasion, (4) grade, and (5) interval from symptom onset to diagnosis. Signet ring or anaplastic lesions were considered high grade. Survival curves were generated on both the overall group and those resected for cure. Multivariate analysis was performed on the overall group. The median age at diagnosis was 19 years (range, 10 to 21). Median follow-up in survivors was 4.7 years. Signet ring tumors occurred in 45% and another 24% were poorly differentiated. Seventy-six percent presented with regional lymph node metastases. The median survival for the overall group was 16 months, whereas that for those undergoing complete resection was 33 months. In patients undergoing resection for cure, grade (P = .005), regional nodal involvement (P = .007), and depth of invasion (P = .03) were significant predictors of outcome in univariate analysis. In the overall group these variables as well as resectability and distant metastases were significant in univariate analysis. In multivariate analysis high-grade lesions and lymph node involvement were highly correlated, as were resectability and metastases. Thus, either variable (but not both) of each pair added information to the multivariate model. In patients resected for cure, positive nodes or high histological grade became the only significant predictors of survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of the acute abdomen in children with leukemia

With the increase in remission and survival in children with acute leukemia, the complication of acute abdomen has become increasingly important in the total care of these children. A total of 286 children with acute leukemia was treated at Memorial Hospital between 1966 and 1971. Sixteen or 5.6% of these children developed an acute abdomen during the course of their disease. During the same period, many other children developed symptoms and signs mimicking an acute abdomen. Of the 9 children treated surgically, 5 were long‐term survivors. Two children treated conservatively died, and 5 patients were diagnosed at autopsy. Prognosis was better in those patients in remission at the time of surgery, and where remission was maintained by immediately restarting antileukemic chemotherapy. A more aggressive surgical approach to the acute abdomen, combined with careful supportive measures, is further adding to the numbers of long‐term survivors in childhood leukemia.