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Background: Recently, the Pigmented Lesion Group at the University of Pennsylvania described a 4-variable model for predicting 10-year survival for patients with primary cutaneous melanoma. The variables are tumor thickness, anatomic site of the lesion, age, and gender. The objective of the current study was to test the validity of this model, employing the large data base of the New York University Melanoma Cooperative Group., Methods: The predicted probabilities of 10-year survival for 780 patients with primary cutaneous melanoma were determined by multivariate logistic regression, using the 4 variables., Results: The overall 10-year survival rate of the current study group was 78.4%. Of the four variables, tumor thickness, anatomic site of the lesion, and age were found to be independent predictors of survival. Although survival was better for women, gender was not a statistically significant factor in predicting 10-year survival when entered into the multivariate logistic regression model. In the current study, the probability of 10-year survival of patients with melanomas < 0.76 mm ranged from 93-99%, depending on the age and primary site. Age and site had more impact on the prognosis of intermediate and thick melanomas than on thin melanomas. Thus, for melanomas 0.76-1.69 mm, 1.70-3.60 mm, and thicker than 3.60 mm, the probabilities of survival ranged from 70-94%, 39-82%, and 23-68%, respectively., Conclusions: The wider ranges in survival rates for thicker melanomas, depending on the other variables, emphasize the importance of including variables in addition to tumor thickness in a prognostic model. Using a large data base from a medical center, the current study supports the prognostic multivariate model of the Pigmented Lesions Group of the University of Pennsylvania; however, the authors of the current study did not find gender to be statistically significant in this multivariate model.

Background: The combined modalities of surgery, chemotherapy, and radiation therapy have greatly improved the survival rate in childhood paratesticular rhabdomyosarcoma, but the incidence of complications and late side effects is a cause for concern., Methods: We reviewed the records of 18 patients treated for paratesticular rhabdomyosarcoma at St. Jude Children's Research Hospital between 1962 and 1989. Patients with Group I disease were treated with orchiectomy, retroperitoneal lymph node dissection, and multi-agent chemotherapy; more advanced cases also received radiation therapy with concurrent chemotherapy., Results: Sequelae included esophageal and common bile duct stricture, inguinal nerve entrapment syndrome, and small bowel obstruction. Short stature was found in all children whose spines were irradiated via para-aortic fields (34-37 Gy) prior to puberty. Two of 18 patients died from treatment complications and one from progressive disease., Conclusions: Multimodality treatment offers an excellent prognosis in paratesticular rhabdomyosarcoma, but is associated with significant morbidity and mortality rates. A discussion of therapy components and their application to disease stages suggests possible approaches to optimizing treatment for this therapy-sensitive malignancy.

Background: Brain metastasis has been considered a rare event in osteosarcoma, although with prolonged survival an increasing incidence has been suggested. There have been no prior reports of long-term survivors among patients with this complication., Methods: The authors describe a child treated for osteosarcoma who is alive and free of disease 8 years after the detection of brain metastases. Of 254 patients with primary osteosarcoma referred to St. Jude Children's Hospital between 1962 and 1989, 13 developed brain metastases, all after relapse or recurrence in another site. Concomitant active lung metastases were present in all of the patients except the one long-term survivor, whose pulmonary disease had responded to treatment with cisplatin and doxorubicin. Log-rank analyses were used to compare survival duration and the frequency of brain metastases among patients treated before and after 1982, when effective multiagent therapy was initiated., Results: Log-rank analyses comparing patients treated before and after 1982 showed that the introduction of effective modern therapy improved survival among patients at risk for brain metastases (i.e., those with recurrent and progressive disease, P = 0.007) but was not associated with a statistically significant increase in the frequency of brain metastases (15.5% versus 4.5%, P = 0.125)., Conclusions: Although the outlook for patients with this complication remains bleak, the resolution of brain metastases after eight courses of ifosfamide in the patient described in this article suggests that enrollment of selected patients in Phase II trials is merited.

Background: Malignant rhabdoid tumor (MRT) is an aggressive, invariably lethal tumor that is resistant to multimodal therapy., Methods: The authors reviewed the clinicopathologic features, treatment, and outcome of 13 children (7 boys and 6 girls) with diagnoses of primary extracranial MRT at St. Jude Children's Research Hospital between 1981 and 1990., Results: The median age at diagnosis was 8 months (range, 10 weeks-18 years). Primary sites included the kidney (seven patients), liver (three patients), soft tissue of scapula, posterior mediastinum, and retroperitoneum. Seven patients had metastatic disease (lungs, six patients; cutaneous hemangioma, one patient). Ten patients had surgical resection of primary tumor (complete, nine patients; incomplete, one patient). Eleven patients had chemotherapy with multiple agents. Three of four chemotherapy responses observed were with regimens containing ifosfamide. Partial responses (PR, > 50% reduction in tumor size) were obtained in one patient who received single-agent ifosfamide during disease relapse (PR lasting 2 months), one patient who received a combination of ifosfamide, carboplatin, and etoposide at diagnosis (PR lasting 5 months), and one patient who was treated with bleomycin, cyclophosphamide, doxorubicin, and vincristine at diagnosis (PR lasting 5 months) and subsequently with ifosfamide in combination with carboplatin and etoposide during disease relapse (PR lasting 4 months). All patients died at a median period of 5 months (range, 0.5-30 months) after diagnosis., Conclusions: Based on this review, the authors recommend using ifosfamide alone or in combination with carboplatin and etoposide in front-line therapy for malignant rhabdoid tumor.

Background: The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH)., Methods: Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation)., Results: The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases., Conclusions: For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.

The need for second-look surgery after chemotherapy in children with advanced germ cell tumors is controversial, particularly when levels of the tumor markers alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta HCG) are elevated at diagnosis. The authors evaluated the outcome of second-look surgery in relationship to tumor marker status in 27 patients with Stage III to IV disease who had completed four courses of chemotherapy. Markers were elevated at diagnosis in 19 patients. After chemotherapy, markers normalized in 12 of these patients. Second-look surgery confirmed complete response (CR) in these 12 patients, two of whom had residual masses on computed tomography (CT) scan (mature teratoma and necrotic tumor). The AFP decreased but did not normalize in seven patients; five had residual disease at second look and the other two later developed measurable disease. Of the eight patients with normal AFP at diagnosis, second look confirmed clinical CR in four. The other four patients had CT evidence of residual masses: surgery showed necrotic tissue in two cases, mature glial elements in one, and mature teratoma with glial elements in one. Thus second-look surgery added no information for treatment planning in children with elevated tumor markers at diagnosis and might best be reserved for patients without tumor markers at diagnosis and residual masses on CT scan, and those with persistent elevation of tumor markers and potentially resectable residual disease. Because of the possibility of small amount of residual tumor, second-look surgery may also be useful in patients whose markers normalize but who have residual masses on CT scans.

Seventy-six patients with classic high-grade osteosarcoma of an extremity received adjuvant chemotherapy by two protocols, initiated in 1972 and 1977, respectively, after appropriate amputations. Chemotherapy consisted of high-dose methotrexate, doxorubicin, and cyclophosphamide. Dose intensity of high-dose methotrexate and doxorubicin was greater for the patients treated with the protocol initiated in 1977. The proportion of long-term disease-free survivors on the two protocols are 46% and 56%. A better outcome (P = 0.042) was seen for the latter group, which received more intensive chemotherapy. Overall, metastases developed in 35 patients; in 19 who were receiving chemotherapy and in 16 after chemotherapy. The outcome for these two protocols, compared with two control groups that were given no chemotherapy or ineffective chemotherapy (biweekly vincristine and cyclophosphamide), confirms the results of controlled studies that showed an advantage of adjuvant chemotherapy after amputation for osteosarcoma.

This is a prelimianry report of an effort to treat women with advanced (Stage III and IV) ovarian cancer who had progressive disease in spite of previous surgery, chemotherapy and/or radiation by a program of reductive surgery, intensive immune stimulation and combination chemotherapy. An initial laparotomy was done where possible to reduce tumor burden, and then all patients were given intravenous corynebacterium parvum (C.P.) in escalating doses over a 10- to 14-day period. Cyclic chemotherapy with Cytoxan, adriamycin and 5-fluorouracil (CAF) was started and repeated monthly. Maintenance subcutaneous C.P. was given weekly. All patients had frequent follow-up clinical and laboratory examination. Immune function was measured by skin tests and in vitro tests prior to treatment and periodically during therapy. Two-thirds of the patients had depressed DNCB and PHA stimulation responses prior to treatment, and almost all had severely depressed lymphocyte counts. Thirty-nine patients entered the program. Exploratory laparotomy was done in 16 patients and in eight, successful tumor reduction was accomplished. Eleven patients received intravenous C. Parvum and all expired before receiving chemotherapy. Four patients received C. Parvum and less than three cycles of CAF; all expired within 2 months. Twenty-four patients received C. Parvum and less than or equal to three cycles of CAF. Four patients had complete regression of measurable disease and were living free of disease 9-12 months after starting CAF. Eight patients had more than 50% regression for a minimum of 3 months, and five were living with disease (LWD) 5-11 months. Five patients had 25% to 50% regression and three were LWD 4-8 months. Seven patients had no regression and all expired within 4 months. Of eight patients who had successful reductive surgery prior to treatment, three were free of disease, median of 10 months, and five had partial responses and were living with disease, a median of 9 months. Although pre-treatment immune function was better in the patients who had a good response to CP and CAF (10 of 12 were DNCB+) vs that in patients with a poor response (4 of 12 were DNCB+) immune function was not significantly improved during therapy. The initial treatment results in this program are encouraging and suggest that this approach may be useful in patients with earlier disease.

The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.

Responses and toxicity after treatment with cisplatin and cisplatin-doxorubicin were compared in two groups of patients with unresectable or metastatic osteosarcoma. Complete or partial responses developed in 3 of 18 individuals treated with cisplatin, and in 5 of 19 after the two-drug combination. Hematologic and gastrointestinal complications were more frequent and severe in patients who received both agents. The combined use of cisplatin and doxorubicin is justified for patients with unresectable or metastatic osteosarcoma at diagnosis because of the potential therapeutic benefits for these individuals.