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Michael P LaQuaglia

Publications and source records attributed to Michael P LaQuaglia.

At least 19 recordsLinked to original sources
PubMed2026

A Clinically Integrated Pediatric Patient-Derived Xenograft Program Enables Evaluation of Cohort and Patient-Specific Biology and Therapeutic Strategies.

UNLABELLED: Preclinical translational research has increasingly utilized patient-derived xenograft (PDX) models for mechanistic and experimental therapeutic studies, yet most existing models have been developed from adult cancer types. We describe the establishment of a PDX program to expand the availability of pediatric-specific PDXs for preclinical research and enable studies of pediatric cancer histologies, including ultrarare diseases. Processes for PDX generation were integrated into established clinical workflows to facilitate universal model generation. Methodologies for tissue procurement, processing, and cryopreservation were optimized to enable intra- and interinstitutional PDX model generation. Over a 6-year span, 388 PDX tumor models representing more than 40 diagnoses were generated, including ultrarare tumors and longitudinal models established from pretherapy, posttherapy, and relapse tumors from the same patient. Genomic characterization of these PDXs demonstrates excellent concordance and recapitulation of molecular alterations of the source tumor. Successful PDX generation was enhanced from relapsed samples, was higher in sarcomas compared with other solid tumor types, and was a negative prognosticator for clinical outcome. With a broad portfolio of molecularly annotated models, we demonstrate utility for validating cross-histology biomarker-driven therapeutic strategies by demonstrating antitumor activity of an MAT2A inhibitor in MTAP-deficient PDXs. Universal model creation also allows for experimental validation of therapeutic hypotheses on a patient-specific basis, as we describe the characterization of a novel RAF1 fusion (EPB41L2::RAF1) in an osteosarcoma PDX. Development of a diverse collection of pediatric PDX models enables hypothesis-driven and cross-histology studies that expand our understanding of cancer biology and aid ongoing drug prioritization efforts in rare tumors. SIGNIFICANCE: A clinically integrated, genomically annotated pediatric PDX portfolio supported by systematic benchmarking of model generation facilitates exploratory biomarker-driven and patient-specific translational studies.

Humans↗
PubMed2006

Liver involvement in neuroblastoma: the Memorial Sloan-Kettering Experience supports treatment reduction in young patients.

BACKGROUND: We reviewed clinical and biologic findings in a series of infants with neuroblastoma (NB) in liver. The aim was to gain insights into improving therapy. PATIENTS AND METHODS: Among 19 newly or recently diagnosed infants with NB in liver, 1987-2002, those with stage 4 involving bone received chemotherapy, while those without bone or extensive bone marrow (BM) involvement were observed or received limited treatment if NB caused life-threatening symptoms. We assessed results in the context of NB treatment risk stratification, which is based on age, stage, and selected biologic features (MYCN, ploidy, histology). RESULTS: Six of eight infants with bone involvement became long-term event-free survivors including 1/2 with MYCN amplification and four who received only 4-6 cycles of chemotherapy; at the end of treatment, four infants had abnormalities in liver +/- the primary site, but these resolved. All 11 infants without bone lesions became long-term survivors with either no cytotoxic therapy or only one cycle of chemotherapy (+/- radiotherapy to liver), including four who had stage 4 and one stage 4S patient who still had NB in BM at age 15 months. CONCLUSIONS: Treatment reduction should be considered for subsets of infants with non-MYCN-amplified widespread NB: stage 4 without bone or extensive BM involvement may not require cytotoxic therapy, stage 4S with symptomatic hepatomegaly may not require multiple cycles of chemotherapy, and classic stage 4 may do well with limited chemotherapy. Persistent liver abnormalities post-treatment may not require continued therapy to achieve a radiologic complete remission.

Bone Marrow Neoplasms↗
PubMed2006

Clinical presentation, treatment, and outcome of alveolar soft part sarcoma in children, adolescents, and young adults.

PURPOSE: Alveolar soft part sarcoma is a rare soft tissue neoplasm that can affect children and adolescents. There are few reported series of these patients in the literature. To define the clinical presentation, treatment, and outcome of young people with this rare sarcoma, we reviewed our clinical experience. METHODS: After institutional review board approval, we examined the records of all patients younger than 25 years old who received treatment at our institution for alveolar soft part sarcoma in the past 30 years. Demographics, tumor sizes, sites and extent of disease, treatments used, progression-free survival, and overall follow-up were evaluated. RESULTS: Each of the 20 patients presented with a mass. Primary disease sites were thigh (n = 8), trunk (n = 6), retroperitoneum (n = 2), and scalp, neck, forearm, and calf (n = 1 each). Metastatic sites included lymph nodes, lung, and brain. Four patients presented to us with incomplete excision of the primary, and 1 had undergone embolization of what was thought to be a vascular malformation. Although wide local excision provided the best chance for a patient to remain free of disease, 14 (70%) of 20 patients exhibited metastases either at presentation or later. Thirty-one metastasectomies were performed. Chemotherapy was used in 11 patients; radiation was used in 8. Median overall follow-up was 36 months; median progression-free follow-up was 12.5 months. Younger patients tended to have Intergroup Rhabdomyosarcoma Study group I disease. Tumors smaller than 5 cm were associated with longer progression-free survival. CONCLUSIONS: Achievement of complete microscopic resection is critical in localized alveolar soft part sarcoma, but incomplete excision and misdiagnosis are often encountered. Despite the occurrence of metastases in 70% of patients, 5-year overall survival was 83%. We found an association between smaller tumor size and longer time to progression. We were not able to demonstrate any benefit from chemotherapy or radiation. Metastasectomies have been performed in multiple long-term survivors.

Adolescent↗
PubMed2006

Computed tomographic scan of the chest underestimates the number of metastatic lesions in osteosarcoma.

PURPOSE: Survival in osteosarcoma correlates with complete resection of primary and metastatic disease. The feasibility of complete pulmonary metastasectomy using thoracoscopy has been raised. Because palpation is not possible, minimally invasive techniques require preoperative radiological enumeration and localization of metastases not presenting at the lung surface. We hypothesized that computed tomographic (CT) scanning underestimated the number of pulmonary metastases in these patients. METHODS: Institutional review board approval was obtained. We determined the association between the number of lesions identified by CT scanning and the number of metastases found at thoracotomies for metastatic osteosarcoma from May 1996 to October 2004. Correlations between CT findings and pathology results were computed using the Kendall tau-b correlation coefficient. Depth, in millimeters, from the pleural surface was measured for those lesions seen on CT scan. RESULTS: We analyzed 54 consecutive thoracotomies performed in 28 patients for whom complete imaging was available. Computed tomographic scanning was performed a median of 20 days before thoracotomy (range, 1-85 days). Correlation between the number of lesions identified by CT and the number of metastases resected at surgery was poor, with a Kendall tau-b correlation coefficient of 0.45 (P < .001). In 19 (35%) of 54 thoracotomies, CT scanning underestimated the number of pathologically proven, viable and nonviable metastases found by the surgeon. Accounting for viable metastases only, correlation between the number of lesions identified by CT and the number of metastases resected at surgery was 0.50 (P < .001), and CT scanning underestimated the number of viable metastases present in 14 (26%) of 54 thoracotomies. Many lesions (32%) were pleural-based, but nearly half (47%) were 5 mm or deeper from the pleural surface of the lung. CONCLUSIONS: Even in the era of modern CT scanning, only a very rough correlation exists between CT findings and the number of lesions identified at thoracotomy. In more than one third of thoracotomies in our series, metastases would have been missed by any tactic besides manual palpation of the lung during open thoracotomy. Minimal access procedures should not be the approach of choice if the goal is resection of all pulmonary metastases in osteosarcoma.

Adolescent↗
PubMed2005

Treatment of osteosarcoma at first recurrence after contemporary therapy: the Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: Overall survival after recurrence of osteosarcoma (OS) is < 30%. The authors reported their experience treating recurrent OS at the time of first recurrence (R1). METHODS: Patients with high-grade OS who achieved complete disease remission (CR) after primary surgery and chemotherapy, and patients who were treated at R1 at Memorial Sloan-Kettering Cancer Center (New York, NY) after 1990 were analyzed by retrospective chart review. RESULTS: For 43 eligible patients, the median time to R1 from initial diagnosis was 21.7 months (range, 4.6-135.7 mos). The lungs were the most common sites of disease recurrence (n = 33 of 43). With a median follow-up of 15.2 months (range, 0.7-158.3 mos) after R1, 15 of 43 (35%) patients were alive. Four of 43 patients were treated with surgery alone (3 patients were alive and 1 had died of progressive disease at the time of last follow-up). Due to unresectable disease, eight patients received only chemotherapy, none of whom survived. For patients with disease recurrence treated with chemotherapy and surgery (n = 31), 22 patients achieved a second CR (CR2). Nine patients were alive and in disease remission (29%) at the time of last follow-up. Twenty-three patients received ifosfamide as part of their retrieval regimen. Of the 18 who achieved a CR2, 8 experienced disease recurrence, 7 remain alive in CR2, and 3 died due to toxicity. Eight patients did not receive ifosfamide. Of these, 4 achieved a CR2 but 3 subsequently experienced disease recurrence. CONCLUSIONS: At R1, 22 of 31 patients achieved a CR2 with aggressive surgery and chemotherapy. The majority of these patients subsequently developed a disease recurrence. Patients appeared to benefit from the addition of ifosfamide to their retrieval regimens. In the end, the role of chemotherapy in recurrent OS continues to remain undefined.

Adolescent↗
PubMed2005

Long-term complications in survivors of advanced stage neuroblastoma.

BACKGROUND: Few studies have assessed late effects in neuroblastoma (NB) survivors, particularly those with advanced stage disease. METHODS: Retrospective analysis of a cohort of advanced stage NB survivors followed in a late effect clinic at a single institution. Screening tests to detect late effects were tailored depending on the individual's treatment exposures. RESULTS: The study included 63 survivors (31 males). The median age at diagnosis was 3.0 years. The median follow-up from diagnosis was 7.06 years. All patients had surgery and received chemotherapy, 89% received radiation therapy (RT), 62% immunotherapy, and 56% autologous stem cell transplant. Late complications were detected in 95% of survivors and included: hearing loss (62%), primary hypothyroidism (24%), ovarian failure (41% of females), musculoskeletal (19%), and pulmonary (19%) abnormalities. The majority of complications were moderate, with only 4% being life-threatening. Survivors who received cisplatin were at greater risk to develop hearing loss compared to those not so treated (OR 9.74; 95% CI: 0.9-101.6). A total dose of cyclophosphamide greater than 7.4 g was associated with ovarian failure (P = 0.02). CONCLUSIONS: Late complications occur frequently in survivors of advanced stage NB. The majority of these problems are of mild-moderate severity. Long-term follow-up (LFTU) and screening of this population is essential.

Adolescent↗
PubMed2005

Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the intestinal tract that typically occur in adults over the age of 40 years. GISTs in younger patients are rare and not well characterized. The objective was to define the characteristics of GISTs in children and young adults (<30 years old). Clinicopathologic and molecular features, including KIT/PDGFRA genotype, in GISTs from 5 children and 10 young adults were analyzed. Gene expression analysis was performed on 5 gastric tumor samples from 2 children, 2 gastric tumors from young adults, and 10 gastric GISTs from older adults using an U133A Affymetrix platform (22,000 genes). All five pediatric GISTs occurred in girls, involved the stomach as multiple nodules, showed predominantly an epithelioid morphology, often involved lymph nodes, and lacked KIT or PDGFRA mutations. Although all five patients developed recurrence (four in the liver, three in the peritoneum, and two in both sites), four are still alive with disease. Of the 10 GISTs in young adults, half occurred in the small bowel and had spindle cell morphology, and one case had lymph node metastasis. KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. Seven patients developed recurrence, and at last follow-up two patients had died of disease. Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors. The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies.

Adolescent↗
PubMed2004

Reduction from seven to five cycles of intensive induction chemotherapy in children with high-risk neuroblastoma.

PURPOSE: We previously reported a high response rate with a dose-intensive chemotherapy regimen in 24 children with high-risk neuroblastoma (NB). We now describe similar results with changes that reduce toxicity (fewer cycles, less vincristine, use of granulocyte colony-stimulating factor). PATIENTS AND METHODS: Eighty-seven consecutive newly diagnosed children with high-risk NB underwent induction that initially had seven cycles (57 patients) but was later limited to five (30 patients). Cycles 1, 2, 4, and 6 used cyclophosphamide (140 mg/kg)/doxorubicin (75 mg/m(2))/vincristine (0.15 mg/kg in the first 27 patients, 0.067 mg/kg subsequently). Cycles 3, 5, and 7 used cisplatin (200 mg/m(2))/etoposide (600 mg/m(2)). Tumor resection followed a minimum of three cycles. The induction was eventually modified to include anti-G(D2) immunotherapy after each of the last three cycles (38 patients). RESULTS: Bone marrow disease resolved in 70 (91%) of 77 patients and was not detected pre- and postinduction in 10 patients. After cycle 3 or 4, 86% of primary tumors were more than 50% smaller. Postinduction metaiodobenzylguanidine scans showed normal radiotracer distribution in metastatic sites in 74 (87%) of 85 patients. Overall results were: 68 (79%) complete/very good partial responses (CR/VGPR); 14 (16%) partial responses (PR); three (3%) less than PR; one (1%) death from infection; and one patient not assessable for response. Five cycles yielded a CR/VGPR rate of 83%, compared with a 77% rate from seven cycles. Side effects were myelosuppression, mucositis, and hearing deficits; neurotoxicity was insignificant with the lower vincristine dosage. Four patients (each received seven cycles) developed myelodysplasia/leukemia. CONCLUSION: Five cycles of this induction regimen, plus surgery, suffice to achieve CR/VGPR in approximately 80% of children with high-risk NB.

Antibodies↗
PubMed2004

Radically different treatment recommendations for newly diagnosed neuroblastoma: pitfalls in assessment of risk.

Neuroblastoma risk stratification is based on stage, age, and biology and prescribes surgery for low-risk disease, moderate-dose chemotherapy for intermediate-risk disease, and maximal therapy (including myeloablative treatment with stem cell transplantation) for high-risk disease. Four cases are described that depict pitfalls in risk assessment with potentially far-reaching consequences. This report focuses on a subset of four patients referred for second opinions. Stage was defined by the International Neuroblastoma Staging System. The first recommendations were for maximal therapy, but second opinions were radically different (ie, surgery alone). Ages at diagnosis were 15 to 25 months. Shimada histopathology was unfavorable in three of the four patients, but chromosomal, serum, and urine prognostic markers were favorable. All four patients did well without cytotoxic therapy (follow-up: 2 years 10 months plus to 4 years 8 months plus). Patient 1 had abdominal and upper thoracic/supraclavicular masses (stage 4); the former was resected and the latter spontaneously regressed. Patient 2 had retroperitoneal disease, without bone marrow involvement, but imaging studies showed lesions in vertebral bodies. Biopsies of the latter showed no neuroblastoma and the primary tumor (with regional lymph nodes) was resected, changing stage from 4 to 2B. Patient 3 had a retroperitoneal mass but no distant disease. Though initially deemed to be unresectable, the abdominal tumor was excised, changing the classification from high risk (stage 3 with unfavorable histopathology) to low risk (stage 1). Patient 4 had a pelvic mass, with unfavorable histopathology, and bilateral inguinal lymph node involvement (stage 3); all soft tissue disease was resected. The absence of cortical bone and extensive bone marrow metastatic involvement in a young neuroblastoma patient should cause a shift in attention to biologic prognostic markers. Some patients classified as having high-risk neuroblastoma might actually do well with no cytotoxic therapy.

Biomarkers↗
PubMed2003

Histone deacetylase inhibitors induce growth suppression and cell death in human rhabdomyosarcoma in vitro.

PURPOSE: A group of histone deacetylase inhibitors has been shown to be effective in suppressing the growth of a variety of transformed cell lines in vitro and in vivo. The effects of two of these agents, suberoylanilide hydroxamic acid (SAHA) and suberoyl-3-aminopyridineamide hydroxamic acid (pyroxamide), were investigated for their growth-suppressive effects on rhabdomyosarcoma (RMS) cells. EXPERIMENTAL DESIGN AND RESULTS: Dose-response experiments of two RMS cell lines, RD (embryonal) and RH30B (alveolar), were performed with SAHA (0.25-3.0 micro M) and pyroxamide (1.25-20.0 micro M). Both agents caused a dose-dependent decrease in viable cell number and an increase in percentage of dead cells over time. Exposure of the RMS cells to SAHA and pyroxamide resulted in an accumulation of acetylated histones with increasing doses by Western blot analysis. Additionally, there was an induction of p21/WAF1 at 15 and 24 h when the cells were cultured with SAHA (2.0 micro M) or pyroxamide (20.0 micro M), concentrations that were tested because they successfully induced inhibition of cell growth and initiated cell death in both RMS cell lines. An increase in nuclei with hypodiploid or sub-G(1) fraction was found by flow cytometry with increasing doses of both SAHA (0.25-3.0 micro M) and pyroxamide (1.25-20.0 micro M) over time. This finding is consistent with DNA fragmentation and cell death by apoptosis. CONCLUSIONS: SAHA and pyroxamide induce growth suppression and cell death in human RMS in vitro. Accumulation of acetylated histones and induction of p21/WAF1 expression are observed in cells exposed to either agent.

Acetylation↗
PubMed2003

Long-term event-free survival after intensive chemotherapy for Ewing's family of tumors in children and young adults.

PURPOSE: To improve the long-term event-free survival of patients with Ewing's family of tumors (EFTs) using high-dose, short-term chemotherapy. PATIENTS AND METHODS: P6 was a prospective study of previously untreated patients with newly diagnosed EFTs. Patients received seven cycles of chemotherapy. Cycles 1, 2, 3, and 6 consisted of cyclophosphamide 2,100 mg/m2/d on days 1 and 2, and a 72-hour continuous infusion of doxorubicin 75 mg/m2 and vincristine 2 mg/m2 starting day 1. Cycles 4, 5, and 7 consisted of 5 consecutive days of ifosfamide 1,800 mg/m2/d and etoposide 100 mg/m2/d. RESULTS: Sixty-eight patients were enrolled from 1991 to 2001 (median age, 18.7 years; range, 3.7 to 39.9 years). At diagnosis, 44 patients had local-regional disease, and 24 had distant metastases. The 4-year event-free survival (EFS) rate for patients with local-regional disease is 82%; overall survival (OS) is 89%. The 4-year EFS rate for patients with distant metastases is 12%; the OS rate is 17.8%. All events occurred within 51 months of diagnosis. Four patients with distant metastases had progressive disease during therapy, and no patient with local-regional disease experienced disease progression during therapy. CONCLUSION: Sustained EFS and OS can be achieved with intensive chemotherapy in children and young adults with local-regional EFTs. This therapy is relatively ineffective in the treatment of metastatic EFTs.

Adolescent↗
PubMed2003

Long-term results of three-dimensional conformal radiation therapy for patients with rhabdomyosarcoma.

BACKGROUND: The authors evaluated the outcome of patients with rhabdomyosarcoma (RMS) who were treated with three-dimensional (3D) conformal radiation therapy (RT) at a single institution. METHODS: The records of all 69 patients with RMS who received 3D RT from 1989 to 2001 were reviewed. All patients received multiagent chemotherapy with or without surgical resection. Follow-up of surviving patients ranged from 1.0 year to 12.8 years (median, 4.3 years). RESULTS: The median patient age was 6 years (range, 1-29 years), and there was a male:female ratio of 1.5:1. Forty-eight patients had embryonal sarcomas, 14 patients had alveolar sarcomas, and 7 patients had undifferentiated sarcomas. The parameningeal area (n = 22 patients) and the trunk (n = 21 patients) were the most common sites. Twelve percent of patients had Stage I disease, 10% of patients had Stage II disease, 51% of patients had Stage III disease, and 27% of patients had Stage V disease. Nine percent of patients were in clinical Group II, 64% of patients were in Group III, and 27% of patients were in Group IV. Regional lymph nodes were involved in 33% of patients, and 77% of tumors measured > or = 5 cm in greatest dimension. The actuarial 5-year local and regional control rates were 90% and 91%, respectively. No predictive factors for local failure were identified; however, alveolar histology was correlated with regional recurrence (29% compared with 4%; P = 0.02). The disease free and overall survival rates were 60% and 63% at 5 years, respectively. Disease stage was most predictive of 5-year survival (76% of patients with Stage I-III disease compared with 24% of patients with Stage IV disease; P < 0.001). CONCLUSIONS: High rates of local control were achieved in patients with RMS using 3D RT. Regional lymph node failure was increased significantly among patients with alveolar histology. Control of metastatic disease remains a formidable problem for patients with Stage IV RMS.

Adolescent↗
PubMed2003

Neuroblastoma in adolescents and adults: the Memorial Sloan-Kettering experience.

BACKGROUND: We reviewed the utility of different treatment modalities in a large series of adolescents/adults with neuroblastoma (NB). PROCEDURE: The 30 adolescents/adults (median age, 19 years) had stage 2B (n = 1), 3 (n = 2), or 4 (n = 27) NB. Treatments included conventional and myeloablative therapy; local radiotherapy (RT); immunotherapy with anti-G(D2) 3F8 monoclonal antibody +/- granulocyte-macrophage colony-stimulating factor (GM-CSF); and 3F8 alternating with low-dose oral etoposide. RESULTS: Seven patients are in first (n = 4) or second (n = 3) complete/very good partial remission (CR/VGPR) at 9+ to 181+ (median, 45+) months. Among 13 newly diagnosed or minimally prior-treated patients, no major responses were seen in 4/4 treated with N4/N5 chemotherapy, but 6/9 treated with the higher dose N6/N7 regimens and surgery had major responses, and immunotherapy produced CR in BM in three patients. Among 17 patients referred because of resistant NB, favorable responses occurred in 6/12 treated with high-dose cyclophosphamide-based salvage therapy, including one patient who is in CR 170+ months after myeloablative consolidation and five patients who achieved CR/VGPR after 3F8/GM-CSF (n = 4) or 3F8/oral etoposide (n = 1). With a median follow-up of 32+ months post-RT, no local relapses occurred in 10/10 patients who received hyperfractionated 21 Gy RT to prevent regrowth of soft tissue masses that had been resected. CONCLUSIONS: High-dose chemotherapy and surgery can achieve a minimal disease state in >50% of newly diagnosed older NB patients. In that setting, local RT, and the use of agents with recently confirmed anti-NB activity, including anti-G(D2) antibodies, and cis-retinoic acid, may improve the poor prognosis of these patients reported to date.

Adolescent↗
PubMed2003

Intraoperative high-dose-rate brachytherapy for pediatric solid tumors: a 10-year experience.

PURPOSE: To evaluate the efficacy and toxicity of intraoperative high-dose-rate brachytherapy (IOHDR) in the management of pediatric solid tumors. METHODS AND MATERIALS: The records of 66 pediatric patients who underwent IOHDR for a solid tumor from February 1993 through December 2002 were retrospectively reviewed. The median age was 7 years (range 9 months to 24 years). Thirty-five patients (53%) were treated for recurrent disease and 24 (36%) had documented metastatic disease. Twenty-nine patients (44%) received both EBRT and IOHDR. The IOHDR dose was prescribed to a depth of 0.5 cm from the surface of a multichannel tissue-equivalent applicator. The median prescription dose was 12 Gy (range, 4-15 Gy). RESULTS: After a median follow-up of 12 months, the 2-year actuarial rates of local control and overall survival were 56% and 54%, respectively, with a median survival of 29 months. Post-operative EBRT significantly improved (p=0.002) 2-year local control (83% v. 29%). Perioperative complications occurred in 8 of 66 patients while late complications occurred in only 3. The actuarial 2-year late complication rate was 12%. Late events that occurred in or near the IOHDR treatment site included small bowel obstruction, broncho-esophageal fistula, and bone growth retardation. CONCLUSIONS: IOHDR is emerging as an integral part of multimodality therapy for pediatric solid tumors as an adjunct to EBRT for local control. IOHDR alone may not be appropriate in the majority of patients. Subacute toxicities occurred rarely and may be related to the combination of extensive surgery, EBRT, and multi-agent chemotherapy in this population.

Adolescent↗
PubMed2003

Congenital and childhood plexiform (multinodular) cellular schwannoma: a troublesome mimic of malignant peripheral nerve sheath tumor.

We present six cases of a plexiform nerve sheath tumor of childhood that previously had been designated a form of malignant peripheral nerve sheath tumor (MPNST), and we provide evidence that such tumors are in fact benign plexiform cellular schwannomas. At presentation, the four girls and two boys ranged in age from 2 to 15 months with tumors of the leg (four), deep groin and upper thigh (one), and pelvis (one). Of the six lesions, five were congenital and none was associated with type 1 neurofibromatosis. Tumor sizes ranged from 2.0 to 9 cm, with three larger than 5 cm. Three tumors were well circumscribed, two were purely infiltrative, and one had a mixed circumscribed and infiltrative growth pattern. Peripheral nerve involvement was evident in two cases. Grossly, the tumors were multinodular or plexiform in configuration and, on sectioning, lobulated and homogeneously tan without necrosis. Characteristic histologic features included hypercellularity, composition of cells spindle in shape with elongate hyperchromatic nuclei, and indistinct cellular outlines. Their nuclei varied minimally in size and shape but were at least three times the size of typical neurofibroma nuclei. Mitoses were seen in every tumor and in the areas of greatest proliferative activity ranged from 4 to 31/10 high power fields. MIB-1 staining of at least 30% of the cells was noted in three cases. In five cases in which p53 immunoreactions were performed, no nuclear staining was evident. That the tumors are schwannomas was evident from their uniform strong staining for S-100 protein and an ultrastructure in all five cases showing only differentiated neoplastic Schwann cells. Architecturally, the tumors differed from conventional schwannoma and nonplexiform cellular schwannomas by their lack of both well-formed capsules and degenerative changes. Follow-up was available in all cases and ranged from 2 to 13.6 years. All tumors recurred locally and were treated by local resections. With the exception of one child lost to follow-up at 25 months, all the children are alive and free of disease. Our data combined with cases previously reported by Meis-Kindblom and Enzinger show a childhood peripheral nerve tumor unassociated with type 1 neurofibromatosis, occurring most commonly in infants, often presenting as a congenital tumor and, though prone to local recurrence, having no metastatic potential. The behavior is that of a benign tumor, although its often rapid growth, hypercellularity and increased mitotic activity, sometimes locally aggressive behavior, and difficulties encountered in obtaining tumor-free margins are unsettling to pathologist and clinician alike. These features may lead to a misdiagnosis of malignancy, which could result in harmful overtreatment.

Biomarkers, Tumor↗
PubMed2003

Curability of recurrent disseminated disease after surgery alone for local-regional neuroblastoma using intensive chemotherapy and anti-G(D2) immunotherapy.

PURPOSE: A reluctance to treat local-regional neuroblastoma by surgery alone derives partly from concern that if widespread neuroblastoma develops, the chance for cure is small, and partly from hope that mild chemotherapy will prevent relapse. The authors report on a series of patients who had distant recurrences after surgery alone for local-regional neuroblastoma. METHODS: Seven patients treated with surgery alone for local-regional neuroblastoma had widespread relapses 2.5 to 25 (median 7) months later and were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). During the period of this study (1995-1999), MSKCC patients with high-risk neuroblastoma received the N7 protocol (dose-intensive chemotherapy, immunotherapy with the anti-G(D2) 3F8 antibody, targeted radiotherapy using 131I-3F8, local radiotherapy) if they had assessable disease, or 3F8 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 13-cis-retinoic acid if they were in remission after treatment elsewhere. RESULTS: Five patients were in complete remission 3 years 11 months to 7 years 4 months from the start of retrieval therapy, including three who received all of their N7 treatment of relapsed neuroblastoma at MSKCC, one who received two cycles of chemotherapy elsewhere before starting N7, and one who was referred for 3F8/GM-CSF because of neuroblastoma cells in pretransplantation bone marrow. CONCLUSIONS: The encouraging survival results of our cohort are consistent with the concept that surgery alone for local-regional neuroblastoma might be beneficial to the overall neuroblastoma population because many patients will never need chemotherapy (and will therefore be spared its potential toxicities), and most of those who do have widespread relapses are likely to be cured with contemporary treatments.

Child↗
PubMed2003

Ewing sarcoma/primitive neuroectodermal tumor of the chest wall: impact of initial versus delayed resection on tumor margins, survival, and use of radiation therapy.

OBJECTIVE: To establish outcome and optimal timing of local control for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the chest wall. METHODS: Patients < or =30 years of age with ES/PNET of the chest wall were entered in 2 consecutive protocols. Therapy included multiagent chemotherapy; local control was achieved by resection, radiotherapy, or both. We compared completeness of resection and disease-free survival in patients undergoing initial surgical resection versus those treated with neoadjuvant chemotherapy followed by resection, radiotherapy, or both. Patients with a positive surgical margin received radiotherapy. RESULTS: Ninety-eight (11.3%) of 869 patients had primary tumors of the chest wall. Median follow-up was 3.47 years and 5-year event-free survival was 56% for the chest wall lesions. Ten of 20 (50%) initial resections resulted in negative margins compared with 41 of 53 (77%) negative margins with delayed resections after chemotherapy (P = 0.043). Event-free survival did not differ by timing of surgery (P = 0.69) or type of local control (P = 0.17). Initial chemotherapy decreased the percentage of patients needing radiation therapy. Seventeen of 24 patients (70.8%) with initial surgery received radiotherapy compared with 34 of 71 patients (47.9%) who started with chemotherapy (P = 0.061). If a delayed operation was performed, excluding those patients who received only radiotherapy for local control, only 25 of 62 patients needed radiotherapy (40.3%; P = 0.016). CONCLUSION: The likelihood of complete tumor resection with a negative microscopic margin and consequent avoidance of external beam radiation and its potential complications is increased with neoadjuvant chemotherapy and delayed resection of chest wall ES/PNET.

Adult↗