Tumor size as a predictor of outcome in pediatric non-metastatic osteosarcoma of the extremity.

BACKGROUND: Better predictors of outcome would allow improved risk-adapted therapy for pediatric nonmetastatic osteosarcoma of the extremity. We investigated the predictive value of MR imaging-based measures of absolute and relative tumor size and volume at the time of diagnosis. We also assessed the relation of tumor size to age and histologic response. METHODS: We retrospectively abstracted demographic, treatment history, and outcome information of patients treated on a single institutional protocol. A single pediatric oncologic radiologist manually measured each primary lesion and the affected native bone in three dimensions on MR images obtained at the time of diagnosis. Eight parameters of tumor size were analyzed for their value in predicting overall survival (OS) and event-free survival (EFS). RESULTS: The median age of the 42 patients was 13.5 years (range: 5.9-18.7 years); 50% were female and 74% were Caucasian. Absolute tumor volume was an important predictor of OS (P < 0.05); absolute tumor depth (analyzed as a continuous variable) was a significant predictor of OS (P = 0.018) and EFS (P = 0.036). Relative measures of tumor size were not found to predict outcome. No relation was seen between tumor size and histologic response. CONCLUSIONS: Absolute tumor size at the time of diagnosis is significantly predictive of OS and EFS. If validated in a larger study, this indicator should be used in the design of risk-adapted treatment protocols for osteosarcoma.

Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of multiagent chemotherapy in the neoadjuvant treatment of retinoblastoma. DESIGN: Noncomparative, prospective case series. PARTICIPANTS: Twenty consecutive patients with multifocal intraocular retinoblastoma (4 unilateral, 16 bilateral [36 eyes]). INTERVENTION: Eight cycles of chemotherapy with carboplatin and vincristine were administered at 3-week intervals over a 6-month period. Supplemental therapy was withheld until disease progression was documented. MAIN OUTCOME MEASURES: Disease progression (defined as tumor growth, vitreous or subretinal seed progression, and new tumor formation), delay of external beam radiotherapy, and ocular survival. RESULTS: Thirty-six eyes were treated. Eighteen eyes had Reese-Ellsworth group I-III tumors, and 16 eyes had Reese-Ellsworth group IV-V tumors at diagnosis. Two patients, who had unilateral disease at diagnosis, subsequently had tumors develop in the contralateral eye. Nineteen of 20 patients (95%) completed eight cycles of chemotherapy without disease progression. Three eyes of three different patients were successfully treated with chemotherapy alone. Thirty-three of 36 eyes (92%) progressed after completion of chemotherapy: 15 of the 18 eyes (83.3%) with Reese-Ellsworth group I-III and 16 of 16 eyes (100%) with Reese-Ellsworth group IV-V tumors. Seventeen eyes (52%) had growth of a tumor, whereas 14 eyes (42%) had progressive vitreous seeding, and 2 eyes (6%) had new tumors develop. Fifteen eyes (42%) required external beam radiotherapy. Twenty-nine of 36 (80.5%) eyes were salvaged. The median follow-up after chemotherapy was 19 months (range, 3-42 months). CONCLUSIONS: Multiagent chemotherapy alone does not ensure a cure for multifocal intraocular retinoblastoma. Supplemental focal therapy is needed to control disease progression.

Dynamic magnetic resonance imaging of regional contrast access as an additional prognostic factor in pediatric osteosarcoma.

BACKGROUND: The purpose of this article was to evaluate the utility of a pharmacokinetically modeled measure of regional contrast access, based on dynamic contrast-enhanced magnetic resonance imaging (MRI) studies after preoperative chemotherapy, as a predictor of disease free survival in osteosarcoma. METHODS: The kinetic parameters of a two-compartment pharmacokinetic model of MRI contrast agent accumulation were analyzed in relation to disease free survival in 31 patients who received protocol-based therapy for nonmetastatic osteosarcoma of the extremities. The modeled exchange rate of contrast between the plasma and the tumor extravascular extracellular fluid space served as a measure of regional contrast access. The prognostic impact of both the clinically accepted standard of histologic evaluation of tumor necrosis and the regional contrast access were analyzed with tumor size as an influential factor. RESULTS: Although the histologic grade of response was not a statistically significant prognostic factor in these patients (P = 0.884), regional contrast access after preoperative chemotherapy was significantly predictive of disease free survival (P = 0.035) in the Cox proportional hazards model. Lower regional access before surgery and smaller tumor size were associated with a better treatment outcome. Log-rank analyses of Kaplan-Meier curves indicated that the impact of regional access was most pronounced in patients with larger tumors (P = 0.052). Higher regional access at presentation also was associated significantly with greater decreases during therapy. CONCLUSIONS: Dynamic MRI estimates of regional contrast access after preoperative chemotherapy, when combined with tumor size, holds promise for the early identification of patients at risk of recurrence. The availability of such response predictors could facilitate the development of risk-adapted treatment approaches.

Secondary ovarian neoplasms in children: imaging features with histopathologic correlation.

BACKGROUND: Although the pathologic features and imaging appearance of childhood primary ovarian neoplasms have been well described, little information is available about the malignancies that may secondarily involve the ovary. OBJECTIVE: To determine the relationship between the imaging features and the histopathology of secondary ovarian neoplasms in children treated at our institution. MATERIALS AND METHODS: We searched our institutional database for codes indicating metastatic ovarian disease. Of the 35 patients with such codes, 18 had pathologically proven secondary ovarian disease. From their medical records we recorded demographic data, presenting symptoms, and evidence of endocrine dysfunction. We reviewed the pre-oophorectomy imaging and the subsequent pathologic specimens. RESULTS: One-third of the patients had bilateral pelvic masses; another third had large masses indistinguishable from the ovaries. Twelve (67%) had either ascites, peritoneal implants, matted bowel, adenopathy, pleural effusions, or some combination of these. Five (28%) had other metastatic disease. Primary tumors included colon adenocarcinoma (9), Burkitt's lymphoma (3), alveolar rhabdomyosarcoma (3), Wilms' tumor (1), neuroblastoma (1), and retinoblastoma (1). CONCLUSION: Although rare, secondary ovarian tumors should be considered in the differential diagnosis of children with ovarian masses. Bilateral ovarian masses or large masses indistinguishable from the ovaries, particularly in the presence of other metastatic foci, may help distinguish primary from secondary ovarian malignancies.

Thallium bone imaging as an indicator of response and outcome in nonmetastatic primary extremity osteosarcoma.

PURPOSE: We investigated one 201Tl bone scintigraphy method as a predictor of histologic response and event-free survival (EFS) of nonmetastatic extremity osteosarcoma. MATERIALS AND METHODS: We evaluated images of the primary tumor to determine whether they exhibited a donut of avidity for 40 patients enrolled on a single institutional protocol. Participants underwent three serial 201Tl bone scintigraphy studies during preoperative neoadjuvant chemotherapy. Intra- and interobserver variability of the method was assessed, and the presence of the donut of avidity was examined as a predictor of EFS and histologic response. RESULTS: Fifty-three percent of patients were female and 75% were Caucasian; the median age at diagnosis was 13.5 years. Intraobserver agreement was moderate to very good, ranging from 0.595 to 0.865. Interobserver agreement was moderate to good for all time points, ranging from 0.576 to 0.708. There was a significant difference in EFS among patients with and without the donut-shape at any of the three time points (P = 0.049); patients whose tumors displayed a donutshape had inferior EFS. CONCLUSION: The pattern of donut avidity in extremity OS is a predictor of lower EFS, but does not correlate with histologic response to therapy.

Metastatic osteosarcoma to the liver after treatment for synovial sarcoma: a case report.

Metastatic osteosarcoma most commonly affects the lungs and other bones. Hepatic metastasis at the time of diagnosis is extremely rare. A 14-year-old boy with synovial sarcoma of the left popliteal fossa was treated with surgical resection, radiotherapy for microscopic residual disease, and 1 year of chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin). Approximately 10 years after the initial diagnosis, a secondary osteosarcoma developed in the left proximal tibia. Computed tomography at presentation showed bilateral pulmonary metastases and large ossified nodules in the liver that demonstrated abnormal avidity on 99mTc MDP bone scan indicating hepatic metastasis. Despite chemotherapy (cisplatin, ifosfamide, high-dose methotrexate, and dacarbazine), the patient died of progressive disease 4 months after the diagnosis of the second cancer. Hepatic metastasis was found at the time of diagnosis of a secondary osteosarcoma and manifested as ossified nodules. The risk of radiation-induced osteosarcoma should always be considered in decisions about treatment for soft-tissue sarcoma.

Prognostic factors and imaging patterns of recurrent pulmonary nodules after thoracotomy in children with osteosarcoma.

BACKGROUND: In children with osteosarcoma who have undergone thoracotomy, it often is difficult to distinguish metastatic from benign recurrent pulmonary nodules. The authors of this study sought to identify any computed tomography (CT) imaging pattern of recurrent pulmonary metastases in this patient population. The authors also sought to identify associated prognostic factors. METHODS: CT scans obtained after thoracotomy were available for 35 patients with osteosarcoma who had undergone resection of presumed pulmonary metastases at St. Jude Children's Research Hospital (Memphis, TN). CT scans obtained before the initial thoracotomy were available for 33 of the 35. The authors recorded location, histologic diagnosis, and time of development of the original pulmonary nodules, time of recurrence of pulmonary disease; the location of recurrent nodules, and the presence of calcification, adenopathy, or progressive pleural disease, as well as patient demographic data, survival data, and location of the primary tumor site. RESULTS: Pulmonary nodules recurred in 32 of the 35 patients after thoracotomy. Nineteen of these patients underwent resection of the recurrent lesions and 1 who died underwent an autopsy; 18 of the 20 patients had metastatic disease. The only CT finding consistently associated with recurrent metastatic disease was progressive pleural thickening, which predicted a poor outcome. The occurrence of a solitary pulmonary nodule in the lung contralateral to the previous surgery was associated almost always with a benign process. CONCLUSIONS: CT imaging cannot distinguish reliably between benign and metastatic recurrent pulmonary disease after thoracotomy in patients with osteosarcoma. Recurrent pulmonary disease in this set of patients is likely to be metastatic, and aggressive surgical intervention is probably warranted. In this study, patients who had progressive pleural disease after thoracotomy consistently experienced pulmonary metastatic recurrence and had a poor prognosis.

Complications of limb-sparing procedures using endoprosthetic replacements about the knee for pediatric skeletal sarcomas.

Ninety-five percent of bone tumors are now managed with limb-sparing techniques. For pediatric patients with bone cancer, such limb reconstruction techniques often involve the placement of large endoprosthetic devices with the goal of improving survivors' quality of life. Nevertheless, few radiologic publications discuss the use of these techniques in children and adolescents. This pictorial essay describes the imaging characteristics of the complications associated with endoprosthetic devices and discusses the conditions that may simulate them.

Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.

PURPOSE: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. PATIENTS AND METHODS: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. RESULTS: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P: = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% +/- 6.7% and 76.4% +/- 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. CONCLUSION: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

Childhood carcinoid tumors: the St Jude Children's Research Hospital experience.

BACKGROUND/PURPOSE: To better characterize childhood carcinoid tumors, the authors reviewed the clinical presentation, treatment, and outcomes of pediatric patients with these rare tumors. METHODS: A retrospective review was conducted of medical records and pathologic materials of all children with carcinoid tumors treated at St Jude Children's Research Hospital between December 1977 and March 1999. RESULTS: Eight patients (median age, 12.7 years) were identified; 2 were boys, and 7 were white. Primary tumor sites were the appendix (n = 5), small intestine (n = 1), bronchus (n = 1), and 1 unknown site. In 7 cases, carcinoid tumor was not suspected at the time the tumor was identified. Seven patients had localized disease; 5 remain disease-free after complete resection, and 2, whose carcinoid tumors were identified incidentally, died of metastatic mucinous adenocarcinoma of the colon. One patient who presented with symptoms of carcinoid syndrome had metastatic disease that responded poorly to cytotoxic chemotherapy and remains alive with active disease. CONCLUSIONS: Although most pediatric carcinoid tumors arise in the appendix, these tumors also occur in other primary sites. Clinical awareness and early diagnosis are important factors in preventing morbidity and mortality. Outcomes are excellent for patients with localized disease that is completely resected, but those with metastatic disease fare poorly. New therapeutic strategies are needed for these patients.

Bone sarcomas of the head and neck in children: the St Jude Children's Research Hospital experience.

BACKGROUND: Bone sarcomas of the head and neck are difficult to resect. The authors reviewed their institutional experience with these tumors to characterize patients' clinical findings and to assess the impact of surgical resection on outcome. METHODS: The records of the 28 patients with bone sarcomas originating in the head and neck treated at St. Jude Children's Research Hospital between March 1962 and January 1998 were reviewed. RESULTS: There were 10 males and 18 females (median age, 12.6 years) each with a single sarcoma: osteosarcoma (18), Ewing sarcoma (7), malignant fibrous histiocytoma (MFH) (2), and fibrosarcoma (1). Primary tumor sites included the maxilla (13), skull (10), mandible (2), and other sites (3). All but one patient with Ewing sarcoma had localized disease at the time of diagnosis. All patients underwent surgery: complete resection, 8; gross total resection, 4; incomplete resection, 14; and biopsy only, 2; 22 also received chemotherapy. Radiotherapy was given to all patients with Ewing sarcoma and to four patients with primary osteosarcoma. Twelve patients survived a median of 8.4 years after diagnosis, 14 died of disease, and 2 died of unrelated causes. Local disease progression was evident in 12 patients (9 with osteosarcoma, 2 with MFH, and 1 with Ewing sarcoma) who died of disease, 9 of whom had the initial treatment of biopsy alone or incomplete resection. Patients with osteosarcoma who had the initial treatment of incomplete resection or biopsy alone were more likely to experience local failure (P = 0.001) and had poorer survival (P = 0.014) than those who underwent complete or gross total resection. CONCLUSIONS: Bone sarcomas of the head and neck are rare among children and most often are localized at the time of diagnosis. Incomplete resection of osteosarcoma is associated with local failure and poor outcome. Although aggressive surgery is essential for the cure of osteosarcoma, its necessity in the treatment of Ewing sarcomas remains controversial.

Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas.

PURPOSE: The aim of this study was to assess renal tubular toxicity (RTT) of ifosfamide-containing regimens (ICR) in patients with newly diagnosed sarcomas at St. Jude Children's Research Hospital. METHODS: The authors reviewed the records of 199 patients receiving ICR at St. Jude between June 1986 and December 31, 1994 for evidence of RTT. Their median age was 13.3 years (range 1.2-24.8); 150 patients were white and 112 were male patients. Diagnoses included osteosarcoma (n = 82), Ewing sarcoma (n = 82), rhabdomyosarcoma (n = 28), and a group of other tumors (n = 7). RESULTS: The authors estimated the proportion of patients with severe RTT during the first five cycles of ICR and within 1 year after therapy for three groups of patients receiving ifosfamide (IFOS, n = 110), ifosfamide/cisplatin (IFOS/CDDP, n = 51), and ifosfamide/carboplatin (IFOS/CARBO, n = 38). The IFOS/CDDP patients received three cycles of IFOS before receiving CDDP and received only 200 mg/m2 by cycle 5, whereas the IFOS/CARBO patients received both agents simultaneously. The authors compared the probability of severe RTT among treatment groups using a generalized linear model for the first five cycles of ICR, as well as the probability of severe RTT within 1 year after therapy among treatment groups for patients receiving all prescribed IFOS using an exact chi-square test with pairwise comparisons when the three-way P value was less than 0.10. The proportion of patients with severe RTT during the first three cycles of ICR was significantly greater in the IFOS/CARBO group than in the other two. Although the proportion of patients with severe RTT in the IFOS/CDDP group increased during cycles 4/5, the proportion of patients with severe RTT remained significantly greater in the IFOS/ CARBO group. Within 1 year after therapy, the proportion of patients with severe RTT differed among the three groups, and pairwise comparisons revealed a significant difference between the IFOS and the IFOS/CDDP group. Severe RTT developed in four IFOS/CDDP patients more than 1 year after therapy, suggesting a long-term effect of CDDP on tubular function. CONCLUSIONS: Chemotherapy regimens including IFOS/ CARBO produce severe acute RTT more frequently than regimens including IFOS or IFOS/CDDP. Patients receiving IFOS/ CDDP appear at risk for delayed RTT. Long-term follow-up of these patients is essential to assess whether the number of patients receiving IFOS/CDDP with severe RTT continues to increase over time and to evaluate the long-term significance of these abnormalities.

Phase I trials in pediatric oncology: perceptions of pediatricians from the United Kingdom Children's Cancer Study Group and the Pediatric Oncology Group.

PURPOSE: To identify areas of concern regarding the conduct of phase I trials, the perceived expectations and motivations of the parents of children entered, the expectations of toxicity and benefit, and the ethical concerns of pediatric hematologists and oncologists in the United Kingdom and North America. METHODS: A survey instrument consisting of 19 open- and closed-ended questions was sent to United Kingdom Children's Cancer Study Group (UKCCSG)- and Pediatric Oncology Group (POG)-affiliated pediatricians. RESULTS: Fifty-three UKCCSG- and 78 POG-affiliated pediatricians responded. Thirty-two UKCCSG and 51 POG respondents had previously entered at least one child into a phase I study. Overall, respondents believed that parents entered their children for medical benefit, altruism, and hope of cure. Although many respondents believed that children could benefit from medical improvement, feelings of altruism, and maintenance of hope, the chance of cure or complete remission was thought to be small. Similarly, parents were thought to potentially benefit through altruism and maintenance of hope. Whereas 83% of UKCCSG respondents indicated that phase I trials were associated with ethical difficulties, this was a concern for 48% of POG respondents. The main ethical concerns of respondents were risk of toxicity, consent of the child, unrealistic hope, and coercion. CONCLUSION: The respondents in this survey expressed mainly ethical concerns regarding the conduct of phase I trials and had realistic expectations of the potential for toxicity and benefit for those children who participate in these studies.

Hemangiopericytoma in children and infants.

BACKGROUND: Hemangiopericytoma (HPC) is a soft-tissue neoplasm most commonly seen in adults; only 5-10% of cases occur in children. Childhood HPC comprises two distinct clinical entities. In children older than 1 year, it behaves in a manner similar to adult HPC. Infantile HPC, however, although histologically identical to adult HPC, has a more benign clinical course. The reasons for these differences in the natural history of HPC are not well understood. METHODS: The authors reviewed the clinicopathologic features of HPC as well as the treatment and outcomes of the 12 children (9 males and 3 females) treated for this disease at St. Jude Children's Research Hospital over a 35-year period. RESULTS: At diagnosis, 9 patients were older than 1 year and 3 were younger than 1 year. Among the 9 older patients, tumors were most commonly found in the lower extremities (n = 5). One patient had been treated for acute lymphoblastic leukemia 15 years earlier. One patient had metastatic disease at diagnosis, and three had unresectable tumors. Two patients experienced objective responses to chemotherapy. Three patients died of disease progression. Among the three infants, two had unresectable disease at diagnosis, and both experienced excellent responses to neoadjuvant chemotherapy. In one case, the response of the tumor to chemotherapy correlated with maturation to hemangioma. All three infants are alive without evidence of disease. CONCLUSIONS: HPC in children older than 1 year does not differ from adult HPC, and aggressive multimodality therapy is required. Infantile HPC, on the other hand, is characterized by better clinical behavior, with documented chemoresponsiveness and spontaneous regression, and requires a more conservative surgical approach. In some cases of infantile HPC, this benign behavior correlates with maturation to hemangioma.

Clear cell sarcoma of soft tissues in children and young adults: the St. Jude Children's Research Hospital experience.

Clear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.

Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study.

PURPOSE: To prospectively study the value of adjuvant chemotherapy in pediatric patients with surgically resected nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS). PATIENTS AND METHODS: From June 1986 to May 1992, after complete surgical resection (+/-radiotherapy) of their NRSTS, 81 eligible patients either received adjuvant chemotherapy comprising vincristine, dactinomycin, cyclophosphamide, and doxorubicin or were observed. Only 30 patients accepted randomization, and 15 were assigned to each regimen. Of the remaining 51 patients, 19 elected adjuvant chemotherapy and 32 elected observation. RESULTS: Patients were predominantly male, and 69% of all patients were white. The median age at diagnosis was 12.3 years (range, 9.2 to 20.7 years). For the 81 eligible patients, the 5-year overall survival estimate was 84.5% +/- 4.4% and event-free survival was 72.2% +/- 5.4%. Among randomized patients, the 5-year estimated overall survival rate was 93.3% +/- 7%, and the event-free survival rate was 86.7% +/- 9.5% for the observation group, compared with 69.2% +/- 13% and 40.7% +/- 14%, respectively, for those who received chemotherapy. The significantly worse outcome of patients who received adjuvant chemotherapy disappeared when survival was stratified by tumor grade. Among all patients, a grade 3 lesion conferred a significant disadvantage with respect to event-free survival (P =.0001). CONCLUSION: The administration of adjuvant chemotherapy according to the schedule and dosages used in our trial did not improve the outcome of children with resected NRSTS. In this study, tumor grade was the most important predictor of clinical outcome in patients with resected NRSTS, and this factor should be incorporated into the stratification of patients in future trials.

Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children.

PURPOSE: In a preclinical model of neuroblastoma, administration of irinotecan daily 5 days per week for 2 consecutive weeks ([qd x 5] x 2) resulted in greater antitumor activity than did a single 5-day course with the same total dose. We evaluated this protracted schedule in children. PATIENTS AND METHODS: Twenty-three children with refractory solid tumors were enrolled onto a phase I study. Cohorts received irinotecan by 1-hour intravenous infusion at 20, 24, or 29 mg/m(2) (qd x 5) x 2 every 21 days. RESULTS: The 23 children (median age, 14.1 years; median prior regimens, two) received 84 courses. Predominant diagnoses were neuroblastoma (n = 5), osteosarcoma (n = 5), and rhabdomyosarcoma (n = 4). The dose-limiting toxicity was grade 3/4 diarrhea and/or abdominal cramps in six of 12 patients treated at 24 mg/m(2), despite aggressive use of loperamide. The maximum-tolerated dose (MTD) on this schedule was 20 mg/m(2)/d. Five patients had partial responses and 16 had disease stabilization. On day 1, the median systemic exposure to SN-38 (the active metabolite of irinotecan) at the MTD was 106 ng-h/mL (range, 41 to 421 ng-h/mL). CONCLUSION: This protracted schedule is well tolerated in children. The absence of significant myelosuppression and encouraging clinical responses suggest compellingly that irinotecan be further evaluated in children using the (qd x 5) x 2 schedule, beginning at a dose of 20 mg/m(2). These results imply that data obtained from xenograft models can be effectively integrated into the design of clinical trials.

Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital.

PURPOSE: The rarity and heterogeneity of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) has precluded meaningful analysis of prognostic factors associated with surgically resected disease. To define a population of patients at high risk of treatment failure who might benefit from adjuvant therapies, we evaluated the relationship between various clinicopathologic factors and clinical outcome of children and adolescents with resected NRSTS over a 27-year period at our institution. PATIENTS AND METHODS: We analyzed the records of 121 consecutive patients with NRSTS who underwent surgical resection between August 1969 and December 1996. Demographic data, tumor characteristics, treatment, and outcomes were recorded. Univariate and multivariate analyses of prognostic factors for survival, event-free survival (EFS), and local and distant recurrence were performed. RESULTS: At a median follow-up of 9.2 years, 5-year survival and EFS rates for the entire cohort were 89% +/- 3% and 77% +/- 4%, respectively. In univariate models, positive surgical margins (P =.004), tumor size > or = 5 cm (P <.001), invasivene (P =.002), high grade (P =.028), and intra-abdominal primary tumor site (P =.055) adversely affected EFS. All of these factors except invasiveness remained prognostic of EFS and survival in multivariate models. Positive surgical margins (P =.003), intra-abdominal primary tumor site (P =.028), and the omission of radiation therapy (P =.043) predicted local recurrence, whereas tumor size > or = 5 cm (P <.001), invasiveness (P <.001), and high grade (P =.004) predicted distant recurrence. CONCLUSION: In this largest single-institution analysis of pediatric patients with surgically resected NRSTS, we identified clinicopathologic features predictive of poor outcome. These variables should be prospectively evaluated as risk-adapted therapies are developed.

Metastases detected at the time of diagnosis of primary pediatric extremity osteosarcoma at diagnosis: imaging features.

BACKGROUND: The authors performed a retrospective study to estimate the incidence rate of metastatic disease at the time of diagnosis of extremity osteosarcoma (OS), to characterize its pattern of presentation, and to identify factors predictive of survival within a cohort of patients with pulmonary metastatic disease at diagnosis. METHODS: From the institutional solid tumor database, the authors identified all patients diagnosed with extremity OS since CT became available at the study institution (1977). The authors recorded patient demographics, the site of primary disease, the histologic subtype of OS, and the presence of metastases at diagnosis. In those patients with pulmonary metastases at diagnosis, the presence of calcifications, the primary tumor volume, the number of pulmonary lobes with disease, and the number of pulmonary nodules were recorded. RESULTS: Of an evaluable population of 215 patients, 32 (15%) had bone or pulmonary metastases at diagnosis, of whom original imaging from 28 patients was available for review. Osteoblastic histology correlated with lung metastases at diagnosis (P = 0.049). One of the 32 patients had a solitary bone metastasis without lung metastases. Four of 28 patients (14%) with original imaging available had calcifications within the pulmonary nodules. Both the number of nodules and the number of lobes involved were found to be significant predictors of survival (P = 0.0009 and P = 0. 04, respectively); multiple nodules were bilateral in 61% of patients. CONCLUSIONS: The rate of incidence of computed tomography detected pulmonary metastases was found to be 14% (31 of 215 patients) at diagnosis and 0.5% (1 of 215 patients) for bone metastases in patients with primary extremity OS. Pulmonary metastases usually are multiple and bilateral and infrequently calcify. The number of nodules and lobes involved are predictors of patient survival.