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Alberto S Pappo

Publications and source records attributed to Alberto S Pappo.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of prognostic factors in patients with nonmetastatic rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: the Children's Oncology Group.

PURPOSE: The outcome for localized rhabdomyosarcoma (RMS) or undifferentiated sarcoma (UDS) is affected by age, histology, primary anatomic site, extent of disease, and therapy. PATIENTS AND METHODS: We evaluated patient and disease characteristics for their ability to predict outcome for patients with nonmetastatic RMS or UDS treated on Intergroup Rhabdomyosarcoma Study (IRS) -III (1984 to 1991) or IRS-IV (1991 to 1997). RESULTS: The estimated 5-year failure-free survival (FFS) rate was 90% for patients with embryonal RMS (ERMS) stage 1, group I or IIa; stage 2, group I; or group III orbit. The estimated 5-year FFS rate was 87% for patients with ERMS stage 1, group IIb or IIc; stage 1, group III nonorbit; stage 2, group II; and stage 3, group I or II; and 73% for patients with ERMS stage 2 or 3, group III. The estimated 5-year FFS rate was poor for patients with stage 2 or 3, group III ERMS with invasive (T2) tumors who were age younger than 1 year or 10 years or older (56%) and patients with stage 2 or 3, group III extremity primary tumors (43%). Overall, outcomes for patients with alveolar RMS (ARMS) or UDS were worse than for patients with ERMS. However, the 5-year FFS rate was good for patients with ARMS/UDS at favorable sites with group I or II (80%) or group III (76%) disease. The FFS rate was poorer for patients with ARMS/UDS at unfavorable sites with group I or II (66%) or group III (45%) disease. The estimated 5-year FFS rate was 31% for patients with group III ARMS/UDS at unfavorable sites with regional lymph node disease, which is similar to metastatic RMS. CONCLUSION: Patient and disease characteristics identify distinct subsets with different outcomes, allowing the Soft Tissue Sarcoma Committee of the Children's Oncology Group to refine risk-adapted therapy assignment.

Adolescent↗
PubMed2006

Pooled analysis of phase II window studies in children with contemporary high-risk metastatic rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

PURPOSE: The Soft Tissue Sarcoma Committee of the Children's Oncology Group has conducted five upfront window trials in patients with newly diagnosed metastatic rhabdomyosarcoma to identify promising new treatment agents. PATIENTS AND METHODS: This pooled analysis identified a total of 420 patients (115 from Intergroup Rhabdomyosarcoma Study III [IRS-III] and 305 from the five window trials). We assessed window therapy response rate, failure-free survival (FFS), and overall survival (OS). RESULTS: Response rates (complete + partial response) assessed at week 6 of window therapy ranged from 41% to 55% and did not predict FFS (P = .073) or OS (P = .31). FFS was influenced by trial (P = .048); patients enrolled onto IRS-III and the ifosfamide/etoposide and ifosfamide/doxorubicin trials fared best. When grouped and compared with topoisomerase I poison trials, ifosfamide/topoisomerase II inhibitor trials had superior FFS (P = .013). However, there was no difference in survival. CONCLUSION: Upfront phase II window trials can efficiently provide robust estimates of activity for new agents and combinations in newly diagnosed patients with high-risk rhabdomyosarcoma. Our data indicate that, for some phase II window trials, the risk of treatment failure may be increased but that the trend towards lower survival for some of the window trials compared with IRS-III is not statistically significant. Window nonresponders did not suffer worse FFS or OS than patients who responded to window therapy. Finally, these results provide a rationale for incorporating ifosfamide, etoposide, doxorubicin, and topoisomerase I poisons in future trials of high-risk metastatic rhabdomyosarcoma.

Adolescent↗
PubMed2006

Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high-risk sarcomas: the St. Jude Children's Research Hospital experience.

BACKGROUND: Intensified chemotherapy may improve the outcome of patients with high-risk pediatric sarcomas. Vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide are highly effective against pediatric sarcomas. The authors investigated the feasibility of administering these agents concomitantly within a defined period. METHODS: In the prospective high-risk sarcoma (HIRISA) Phase II trial HIRISA1, pediatric patients with high-risk sarcomas received 3 cycles of intensive vincristine, ifosfamide, etoposide, cyclophosphamide, and doxorubicin (VACIE) before radiotherapy and/or surgery began at Week 9 with concurrent vincristine, cyclophosphamide, and doxorubicin (Week 9) and vincristine and ifosfamide (Week 12). Three additional cycles of VACIE were then given. After delayed hematologic recovery in the first 11 patients, the protocol was modified (HIRISA2) to delay local control therapy until after 5 cycles of VACIE (to be completed within 18 weeks). Patients who responded to the protocols were eligible for myeloablative consolidation with autologous stem cell support. RESULTS: Eleven of 24 patients (median age, 14.9 years) had Ewing sarcoma family of tumors, 9 patients had rhabdomyosarcoma, and 4 patients had unresectable desmoplastic small round cell tumors. Seven of 13 patients on HIRISA2, but none of 11 patients on HIRISA1, completed therapy within the specified time. Reversible Grade 4 myelosuppression was the most common toxicity. Major nonhematologic toxic effects were mucositis, nutritional impairment, hypotension, and peripheral neuropathy. Three patients died of toxicity. The 5-year survival and 5-year event-free survival estimates both were 45.8% +/- 11.2%. CONCLUSIONS: The feasibility of administering intensive chemotherapy regimens like VACIE was dependent in part on the timing of local control therapy. This regimen was associated with significant toxicity.

Adolescent↗
PubMed2006

New drugs for the treatment of metastatic or refractory soft tissue sarcomas in children.

Children with relapsed, recurrent or metastatic sarcomas represent a therapeutic challenge for the pediatric oncologist. Strategies for the development of newer therapies for children with these sarcomas have, in the past, been histology-specific. For example, drug development in rhabdomyosarcoma has relied upon the preclinical xenograft model, whereas therapies for pediatric nonrhabdomyosarcomatous soft tissue sarcomas have mostly been derived from adult trials. The progress to date and the tools used in the treatment of advanced pediatric sarcomas will be summarized in this review.

Animals↗
PubMed2005

Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study.

PURPOSE: To describe the response rate and survival of children and adolescents with unresected or metastatic nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) treated with vincristine, ifosfamide, and doxorubicin. PATIENTS AND METHODS: Between September 1996 and June 2000, 39 eligible patients received vincristine (1.5 mg/m(2) weekly for 13 doses), ifosfamide (3 g/m(2) daily for 3 days every 3 weeks for seven cycles), doxorubicin (30 mg/m(2) daily for 2 days for six cycles), and mesna (750 mg/m(2) for four doses after ifosfamide). Granulocyte colony-stimulating factor was administered daily (5 mug/kg) after each cycle of chemotherapy. Radiotherapy was administered from weeks 7 through 12. RESULTS: The median patient age at diagnosis was 11.7 years; the most common primary tumor site was lower extremity (36%); and synovial sarcoma was the predominant histology. More than three fourths of all tumors were 5 cm or greater at their largest diameters. The overall objective combined partial and complete response rate was 41% (95% CI, 25.7% to 56.7%). The estimated 3-year overall survival and progression-free survival rates (+/- standard deviation) for eligible patients were 59% +/- 8.2% and 43.6% +/- 7%, respectively. Patients with clinical group III disease had significantly better 3-year and progression-free survival rates compared with patients who presented with metastatic disease. CONCLUSION: The vincristine, ifosfamide, and doxorubicin regimen was moderately active against pediatric NRSTS. Patients with synovial sarcoma had higher response rates than other patients, and patients with unresected disease had improved outcomes. Patients with metastatic disease continue to fare poorly, and newer approaches are indicated for these patients.

Adolescent↗
PubMed2005

Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is rare in children, accounting for <1% of all cases. Treatment most commonly includes radiotherapy but long-term side effects of such treatment can produce devastating cosmetic and functional sequelae in children. Chemotherapy may help to decrease the radiotherapy dose and limit the side effects of local therapies. However, little is known regarding the chemosensitivity of NPC tumors in pediatric patients. METHODS: Patients with American Joint Committee on Cancer (AJCC) Stage I/II disease (Stratum 01) received irradiation only. Patients with AJCC Stage III/IV disease (Stratum 02) received 4 courses of preradiation chemotherapy comprising methotrexate (120 mg/m2) on Day 1, with cisplatin (100 mg/m2) 24 hours later, 5-fluorouracil 1000 mg/m2 per day as a continuous infusion for 3 days, and leucovorin 25 mg/m2 every 6 hours for 6 doses. Irradiation was given after chemotherapy and consisted of 50.4 gray (Gy) to the upper neck and 45.0 Gy to the lower neck, with a boost to the primary tumor and positive lymph nodes for a total dose of 61.2 Gy. RESULTS: One patient was enrolled in Stratum 01 and 16 evaluable patients were enrolled in Stratum 02. The median age of the patients was 13 years and 65% of the patients were black. All patients tested had evidence of Epstein-Barr virus infection. Two-thirds of the patients developed Grade 3-4 mucositis during chemotherapy. The overall response rate to induction chemotherapy was 93.7%. The overall 4-year event-free and overall survival rates (+/- the standard error) were 77%+/-12% and 75%+/-12%, respectively. CONCLUSIONS: The current study demonstrated that childhood NPC was sensitive to chemotherapy and that chemotherapy before irradiation was feasible. Future trials should investigate equivalent efficacy with a reduced radiotherapy dose.

Adolescent↗
PubMed2005

The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma.

BACKGROUND: It has been shown that induction high-dose interferon alpha-2b (IFN-alpha-2b) followed by maintenance therapy improves recurrence-free survival in adults with high-risk, resected melanoma. In this study, the feasibility and toxicity of this regimen were evaluated in newly diagnosed pediatric patients with Stage III melanoma involving regional lymph nodes. METHODS: Fifteen patients age <or=18 years with newly diagnosed Stage III melanoma were enrolled on an institutional protocol. Patients were treated with wide local excision, sentinel lymph node biopsy, lymph node dissection, and adjuvant biotherapy, consisting of induction therapy with 20 million IU/m2 per day IFN-alpha-2b intravenously 5 times per week for 4 weeks followed by maintenance therapy with IFN-alpha-2b 10 million IU/m2 per day subcutaneously 3 times per week for 48 weeks. Patients were monitored for toxicity and tumor recurrence. RESULTS: All patients completed induction therapy, and nine patients completed maintenance therapy. Three patients currently are receiving maintenance, 2 patients developed recurrent disease on maintenance therapy, and 1 patient stopped maintenance therapy 5 weeks early. During induction therapy, Grade 3-4 toxicities included 14 episodes of neutropenia in 11 patients, 3 episodes of leukopenia in 2 patients, and 6 episodes of liver transaminase elevations in 5 patients. Dose modifications were required in four patients. During maintenance therapy, Grade 3-4 toxicities included 23 episodes of neutropenia in 10 patients and 2 episodes of liver transaminase elevations in 2 patients. Three patients required dose modifications. All toxicities were reversible with interruption or dose modification of therapy, and no patients were taken off study due to toxicity. CONCLUSIONS: High dose IFN-alpha-2b for 4 weeks followed by a lower dose maintenance phase for 48 weeks was feasible in children with Stage III melanoma and was associated with tolerable toxicity.

Adolescent↗
PubMed2005

Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans.

To document the clinical activity of imatinib mesyalte in a child with a dermatofibrosarcoma protuberans (DFSP). An 18-month-old girl presented with a large extremity DFSP. As surgical resection would have caused unacceptable functional defects, imatinib mesylate was administered to induce tumor reduction and or stabilization. After 23 weeks of therapy, magnetic resonance imaging (MRI) of the tumor showed a reduction in the subcutaneous thickness in the transverse plane. The drug was tolerated well without any adverse reactions. Imatinib mesylate offers a non-surgical alternative for the treatment of large DFSP in children.

Benzamides↗
PubMed2005

Clinical and molecular characteristics of pediatric gastrointestinal stromal tumors (GISTs).

BACKGROUND: To describe the clinical characteristics, molecular features, treatment, and outcome of six pediatric patients with gastrointestinal stromal tumors (GISTs). PATIENTS AND METHODS: Retrospective clinical review of GISTs, seen at The Hospital for Sick Children (HSC) Toronto, over an 11-year period. All specimens were stained for the CD 117 and CD 34 antigens. Three specimens were sequenced for mutations in exons 9, 11, and 13 of the c-kit gene. RESULTS: Five patients were evaluated and treated at HSC and one was referred for histopathological consultation only. The median patient age at diagnosis was 13.6 years, (6.9-14.8 years); four were female. All patients presented with anemia secondary to gastrointestinal (GI) bleeding. The disease was localized in five patients and two had other malignancies consistent with the diagnoses of Carney's triad. Immunohistochemical staining for CD 117 and CD 34 showed heavy cytoplasmic localization in all of the tumor cells. A novel point mutation of KIT in codon 456 of exon 9 was found in one case. Complete surgical resection was achieved in the five patients managed at our center and none received adjuvant therapies. Disease recurred locally in one patient. Four patients are alive and one is lost to follow-up. CONCLUSIONS: In children and adolescents, GISTs should be considered in the differential diagnosis of anemia secondary to GI hemorrhage. The absence of an exon 11 mutation and the identification of a novel mutation in exon 9 suggest that pediatric GISTs may respond differently to currently available targeted therapies and therefore should be studied within the context of collaborative group trials.

Adolescent↗
PubMed2005

Remote intrapulmonary spread of recurrent respiratory papillomatosis with malignant transformation.

Recurrent respiratory papillomatosis is the most common neoplasm of the larynx in childhood. Extension into lung parenchyma occurs in less than 1% of patients and has a low risk of malignant transformation. Treatment options for intrapulmonary spread have shown limited success. We describe a case of recurrent respiratory papillomatosis with extensive parenchymal involvement and adenosquamous carcinoma in a 14-year-old girl.

Adolescent↗
PubMed2005

Predictors of outcome in children and adolescents with rhabdomyosarcoma of the trunk--the St Jude Children's Research Hospital experience.

PURPOSE: The aim of this study was to determine predictors of outcome in childhood truncal rhabdomyosarcoma. METHODS: Retrospective chart review evaluating the impact of demographic features, disease characteristics, and the extent and timing of surgical intervention on outcome was performed. RESULTS: Thirty-three patients with a median age of 8 years were identified. Most had advanced Intergroup Rhabdomyosarcoma Study group III (n = 13) or group IV (n = 9) disease. Primary site included 20 (61%) chest wall, 6 (21%) paraspinal, 5 (15%) periscapular, and 1 (3%) abdominal wall. Most tumors were embryonal (n = 21), larger than 5 cm (n = 27), and locally invasive (n = 13); 7 had positive nodes. Tumor size, nodal status, and gross total tumor resection (upfront or delayed) were significant predictors of event-free and overall survival. Tumors 5 cm or smaller were amenable to upfront surgical resection (P = .007). In patients with tumors larger than 5 cm, resection at any time was associated with a 10-year overall survival 57% +/- 13% compared with 8% +/- 5% in those who had no surgery (P = .003). Tumor recurrence was local in 44% of cases, and survival after local recurrence was rare (1 of 8). CONCLUSION: Tumor size, nodal status, and gross total resection at any time are significant predictors of outcome in truncal rhabdomyosarcoma. Gross tumor excision should be the goal of surgical intervention in this disease.

Abdominal Neoplasms↗
PubMed2004

Brain metastases of malignant germ cell tumors in children and adolescents.

BACKGROUND: Brain metastases of pediatric germ cell tumors are uncommon, and there is limited information regarding their incidence, clinical presentation, response to treatment, and influence on survival. METHODS: The authors reviewed the experience with brain metastases from pediatric germ cell tumors at St. Jude Children's Research Hospital (Memphis, TN) over a 40-year period. RESULTS: Between March 1962 and February 2002, 16 of 206 patients with germ cell tumors (7.8%) had brain metastases at the time of initial presentation (n = 2), later in the course of the illness (n = 12), or at autopsy (n = 2). Twelve of 16 patients (75%) had symptoms referable to the brain (nausea/emesis, headaches, or seizures), and 14 (88%) had pulmonary metastases at the time brain metastases were identified. Patients with brain metastases were more likely to have an extragonadal primary tumor (P = 0.013), advanced-stage disease at initial presentation (P = 0.016), and choriocarcinoma within the primary tumor (P < 0.001). The incidence of brain metastases was significantly lower in the second 2 decades of the study period (5 of 135 patients [3.7%]) than in the first 2 decades (11 of 71 patients [15.5%]; P = 0.005). Two of the 16 patients in the current study are long-term survivors. CONCLUSIONS: Brain metastases are uncommon in childhood germ cell tumors, and their incidence appears to be decreasing. In the current study, most patients with such metastases were symptomatic and had pulmonary metastases at the time brain metastases were identified. Patients with the highest risk of developing brain metastases include those with extragonadal tumors, those with high disease stage at initial presentation, and those with choriocarcinoma as a component of the primary tumor. The probability of survival is poor, although a small proportion of patients may become long-term survivors.

Adolescent↗
PubMed2004

Pediatric gastrointestinal stromal tumors and leiomyosarcoma.

BACKGROUND: With the introduction of molecularly targeted therapy for gastrointestinal stromal tumors (GISTs), it became important to distinguish GISTs from leiomyosarcomas (LMSs). The authors sought to characterize the clinicopathologic features of these tumors in pediatric patients. METHODS: The authors reviewed the medical records of 11 patients for whom GIST or LMS was diagnosed between March 1962 and July 2002 at St. Jude Children's Research Hospital and reclassified the tumors according to current histologic and immunophenotypic criteria. The authors also reviewed the literature pertaining to pediatric GISTs and LMSs. RESULTS: Seven patients had GISTs, and four had LMS. The median age of the patients at diagnosis was 11.5 years. At diagnosis, metastases were present in one patient with GISTs and in another with LMS. Unlike the focal distribution of CD117 (KIT) in LMS, diffuse and strong immunostaining was observed in GISTs. Only GISTs expressed CD34. Six patients underwent complete resection (four with GISTs and two with LMS), four patients underwent incomplete resection (three with GISTs and one with LMS), and one patient (with LMS) underwent a biopsy only. Radiotherapy or chemotherapy was used to treat one patient with GISTs and three patients with LMS. One patient with a high-risk GIST (largest dimension of 32 cm and high mitotic count) was treated with adjuvant imatinib mesylate outside the preferred setting of a clinical trial, due to concerns regarding the high risk of tumor recurrence. Four patients with GISTs and two with LMS survived median disease-free a median of 10.4 years and 4.3 years after diagnosis, respectively. Tumors in all but one survivor were completely resected. CONCLUSIONS: KIT staining helped to distinguish GISTs from LMSs. Surgery was the treatment of choice for both entities, and tumor resectability was a key prognostic factor.

Adolescent↗
PubMed2004

Late events occurring five years or more after successful therapy for childhood rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

The aim of our study was to describe late failures in children who initially survived event-free five years from a diagnosis of rhabdomyosarcoma. Charts of children enrolled in the Intergroup Rhabdomyosarcoma Study Group (IRSG) trials III, IV pilot and IV (1984-1997) who survived five years event-free and subsequently experienced an adverse event (disease recurrence, second malignant neoplasm or death from other causes) were reviewed. Of the 2534 enrolled patients, 1160 were event-free at five years and 48 subsequently experienced a late event. The estimated 10-year event rate for the 1160 patients who were alive and event-free at five years was 9% (95% Confidence Interval (CI) 5%, 13%). Patients with both advanced disease (Group III/IV) and large primary tumours at diagnosis (> 5 cm) were at the highest risk for late events (19%; 95% CI 8%, 30%). Late events after successful treatment for rhabdomyosarcoma occur in 9%. Those with advanced disease and large primary tumours have the highest risk of late events.

Adolescent↗
PubMed2004

Metastatic rhabdomyosarcoma: a retrospective review of patients treated at the hospital for sick children between 1989 and 1999.

Children with metastatic rhabdomyosarcoma (RMS) continue to fare poorly (3-year survival 20-30%). Various therapies, including end-intensification with high-dose chemotherapy and stem cell support, have been used in an attempt to improve the outcome of these patients. The authors reviewed their clinical experience over a 10-year period to identify predictors of outcome in these patients. The authors reviewed the clinical characteristics, treatment, and outcome of all patients with metastatic RMS diagnosed and treated at the Hospital for Sick Children between 1989 and 1999. Kaplan-Meier curves were generated to compare survival and failure-free survival of different subgroups of patients. Differences between groups were analyzed using univariate analysis and the log-rank test. Seventeen patients with metastatic RMS were identified. Thirteen patients were treated with standard chemotherapy +/- radiotherapy and four received high-dose end-intensification therapy with stem cell support. The estimated 3-year overall survival (OS) and failure-free survival rates for all patients were 35% (95% CI 13-58) and 29% (95% CI 18-40), respectively. Patients with embryonal histology, metastases confined to the lung, and age younger than 10 years had a 3-year OS of 100%, compared with an OS of 0% for the remaining patients (P < 0.0006). The median follow-up for the five survivors was 5.5 years. The authors have identified a subset of children with metastatic RMS having embryonal histology, age less than 10 years, and only pulmonary metastases who have favorable survival outcomes when treated with chemotherapy with or without stem cell support.

Child↗
PubMed2003

Malignant fibrous histiocytoma and other fibrohistiocytic tumors in pediatric patients: the St. Jude Children's Research Hospital experience.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is a controversial entity. In the current study, the authors reviewed their institutional experience with these tumors to characterize their clinical features in pediatric patients and assess the impact of surgical resection on outcome. METHODS: The records of the 28 patients who were diagnosed with MFH or MFH variants of soft tissue between January 1971 and December 2000 were reviewed and the tumors were reclassified according to the World Health Organization guidelines. RESULTS: Seventeen patients had MFH; 10 patients had angiomatoid fibrous histiocytoma (FH), and 1 patient had a plexiform fibrohistiocytic tumor. The median age of patients at the time of diagnosis was 7.3 years. The most common primary tumor site was the extremity (n = 14). Metastatic disease (to the lung) was present in only three patients, each of whom had MFH. Of the 17 MFH tumors, 13 were high grade, 8 were invasive, and 6 measured > 5 cm. All angiomatoid FH tumors and the plexiform fibrohistiocytic tumor were noninvasive, and 10 measured < or = 5 cm. Surgical treatment was comprised of wide local excision with clear margins (n = 18), amputation (n = 3), excision with positive or indeterminate surgical margins (n = 4), partial resection (n = 2), or biopsy only (n = 1). Primary reexcision was performed for 21 patients. The 5-year survival and event-free survival (EFS) estimates for patients with MFH were 76.5% +/- 11.2% and 70.6% +/- 12.1%, respectively; the 5-year survival and EFS estimates were 100% +/- 0% for patients with angiomatoid FH or plexiform fibrohistiocytic tumor. Compared with partial resection or excision, wide local excision or amputation was found to have a positive impact on the probability of EFS in patients with localized disease (P = 0.008). All four patients with metastatic or unresectable MFH had died by the time of last follow-up. CONCLUSIONS: MFH should be distinguished from angiomatoid FH and plexiform fibrohistiocytic tumors, both of which are less aggressive. Wide local excision is the treatment of choice, regardless of the histology or grade of the tumor. Patients with metastatic or unresectable MFH appear to have a poor outcome and would benefit from more effective therapies.

Adolescent↗