Publications (13)52.49 Total impact
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Article: Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and -IV, 1984-1997: A report from the Children's Oncology Group.
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ABSTRACT: BACKGROUND: We wanted to ascertain patterns of recurrence, re-treatment, and outcome among 188 eligible patients treated for localized orbital sarcoma on IRSG Protocols III/IV, 1984-1997. PROCEDURE: Retrospective chart review. RESULTS: Twenty-four of 188 patients (12.8%) developed local (n = 22) or distant relapse (n = 2) at 0.057-7.05 years (median, 1.58) after enrollment. Ages at study entry were 0.14-17 years (median, 5 years). Initial tumor operations included biopsy (n = 20) or gross resection with microscopic residual (n = 4). Initial tumor diameters were 0.5-7 cm (median, 3). Pathologic subtypes were embryonal rhabdomyosarcoma (ERMS, n = 19), sarcoma not otherwise specified (n = 2), and alveolar RMS, botryoid ERMS, or undifferentiated sarcoma (n = 1 each). Initial treatment included vincristine/dactinomycin (n = 24) including an alkylator (n = 4) and radiotherapy (RT, n = 21). Twenty patients responded, 14 completely, 6 partially. After recurrence, patients underwent orbital exenteration (n = 10), enucleation (2), tumor excision (3), or biopsy (1); 7 had no operation, and 1 had no data. Post-relapse chemotherapy included combinations of etoposide (n = 14 patients), doxorubicin (14), ifosfamide (12), cyclophosphamide (7), and dacarbazine (n = 1). Six patients received RT, including four previously treated and two not irradiated initially. Two patients died; one at 1.79 years after contralateral brain metastasis followed by local recurrence, and another at 2.49 years after multiple local recurrences. Twenty-two patients (91.7%) survived sarcoma-free for 0.04-17 years (median, 6.9) after relapse, and 18 of 22 (82%) were alive ≥5 years after relapse. CONCLUSION: Survival following recurrent localized orbital sarcoma appears likely after vigorous re-treatment given with curative intent. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.Pediatric Blood & Cancer 09/2012; · 1.89 Impact Factor -
Article: Influence of noncompliance with radiation therapy protocol guidelines and operative bed recurrences for children with rhabdomyosarcoma and microscopic residual disease: a report from the Children's Oncology Group.
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ABSTRACT: Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control. All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumor excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation. Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children. Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.International journal of radiation oncology, biology, physics 06/2011; 80(2):333-8. · 4.59 Impact Factor -
Article: Orbital sarcoma with metastases at diagnosis: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
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ABSTRACT: We reviewed clinicopathologic features and treatment outcomes in seven patients diagnosed with Stage 4/Group IV orbital sarcoma and treated on IRSG protocols I-III. Three patients had embryonal rhabdomyosarcoma (RMS), and two patients each had alveolar RMS or unclassified sarcoma. Median age at diagnosis was 1.8 years (range 0.2-6.9 years). All patients had bone marrow involvement, including six with normal complete blood count at diagnosis. Cerebrospinal fluid was normal in six patients. Three patients survived >5 years, including one with local recurrence. In conclusion, further study is needed to determine necessity of bone marrow and CSF examination in orbital sarcoma patients.Pediatric Blood & Cancer 02/2010; 54(7):1045-7. · 1.89 Impact Factor -
Article: The impact of surgical excision in chest wall rhabdomyosarcoma: a report from the Children's Oncology Group.
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ABSTRACT: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor of childhood. Patient age, size, histologic finding, and site of the tumor are primary determinants of prognosis in RMS. Chest wall RMS is a site in which the limitations of surgical excision are realized. We aim to determine the impact of surgical excision in chest wall RMS. A retrospective chart review was conducted of all 130 pediatric patients enrolled in the Intergroup Rhabdomyosarcoma Study (IRS) with chest wall rhabdomyosarcoma from the first (I) through fourth (IV) IRS with follow-up to June 2005. Median follow-up was 12.1 years (4.6-27.2 years). There was a significant improvement in failure-free survival (FFS) and overall survival (OS) between the first IRS study, I, and IRS-IV. The estimated FFS and OS at 5 years in IRS I was 30% and 40%, respectively, compared to 68% and 78%, respectively, in IRS-IV (P = .03 and P = .05, respectively). There was no association between histologic finding or size and FFS or OS. However, all patients who presented without metastasis had an FFS and OS of 49% and 61%, respectively, compared with metastatic patients, 7% and 7%, respectively (P < .001). Five-year FFS of group I, II, and III patients was 52%, 52%, and 45%, respectively, and OS was 65%, 60%, and 59%, respectively. There was no significant difference in 5-year FFS or OS in patients who had a complete resection (group I), complete resection with positive microscopic margins (group II), or biopsy or partial resection only (group III). In groups I to III patients, the local and regional failure rate at 5 years is 25% and 6%, respectively. The most significant impact on outcome in chest wall RMS patients is metastatic disease at diagnosis. The locoregional failure rate is high but does not appear to impact survival. Alternative treatment strategies are needed for chest wall RMS, but aggressive surgical excision may not be necessary.Journal of Pediatric Surgery 05/2008; 43(5):831-6. · 1.45 Impact Factor -
Article: Assessment of response to induction therapy and its influence on 5-year failure-free survival in group III rhabdomyosarcoma: the Intergroup Rhabdomyosarcoma Study-IV experience--a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
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ABSTRACT: Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS. We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response. Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS. In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.Journal of Clinical Oncology 12/2007; 25(31):4909-13. · 18.37 Impact Factor -
Article: Pediatric surgical oncology: management of rhabdomyosarcoma.
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ABSTRACT: A malignant tumor of striated muscle origin, Rhabdomyosarcoma (RMS) is a childhood tumor that has benefited from 30 years of multimodality therapeutic trials culminating in a greater than 70% overall current 5-year survival. Prognosis for RMS is dependent on anatomic primary tumor site, age, completeness of resection, presence and number of metastatic sites, histology and biology of the tumor cells. Multimodality treatment is based on risk stratification according to pretreatment stage, postoperative group, histology and site. Therefore, pretreatment staging is vital for assessment and is dependent on primary tumor site, size, regional lymph node status, and presence of metastases. Unique to RMS is the concept of postoperative clinical grouping that assesses the completeness of disease resection and takes into account lymph node evaluation both at the regional and metastatic basins. At all sites, if operative resection of all disease is accomplished, including microscopic disease, survival is improved. Therefore, the surgeon plays a vital role in determining risk stratification for treatment and local control of the primary tumor for RMS.Surgical Oncology 12/2007; 16(3):173-85. · 2.44 Impact Factor -
Article: Antiparallel segregation of notch components in the immunological synapse directs reciprocal signaling in allogeneic Th:DC conjugates.
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ABSTRACT: Direct T cell allorecognition underlies the development of a vigorous immune response in the clinical setting of acute graft rejection. The Notch pathway is an important regulator of Th immune responses, yet the molecular underpinnings of directional Notch signaling, otherwise critical for binary cell fate decisions, are unknown during autologous or allogeneic Th:DC interactions. Using the development of immune synapses (IS) in the allogeneic, human physiological Th:DC interaction, we demonstrate that Th-Notch1 receptor and DC-Notch ligands (Delta-like1, Jagged1) cluster in their apposed central-supramolecular-activation-clusters (cSMAC), whereas DC-Notch1 receptor and Th-Notch ligands cluster in their apposed peripheral-SMAC (pSMAC). Numb, a negative regulator of Notch, is excluded from the IS-microdomains where Notch1 receptor accumulates. This antiparallel arrangement across the partnering halves of the IS supports reciprocal Notch signal propagation in the DC-to-Th direction via the cSMAC and Th-to-DC direction via the pSMAC. As a result, processed Notch1 receptor (Notch-intracellular-domain, NICD1) and its ligands, as well as their downstream targets, HES-1 and phosphorylated-STAT3, accumulate in the nuclei of both cell-types. There is also enhancement of GLUT1 expression in both cell-types, as well as increased production of Th-IFN-gamma. Significantly, neutralizing Notch1R Ab inhibits NICD1 and HES-1 nuclear translocation, and production of IFN-gamma. In contrast, the IS formed during Ag-nonspecific, autologous Th:DC interaction is immature, resulting in failure of Notch1 receptor segregation and subsequent nuclear translocation of NICD1. Our results provide the first evidence for the asymmetric recruitment of Notch components in the Th:DC immunological synapse, which regulates the bidirectional Notch signal propagation.The Journal of Immunology 08/2007; 179(2):819-29. · 5.79 Impact Factor -
Article: Significance of persistent mature rhabdomyoblasts in bladder/prostate rhabdomyosarcoma: Results from IRS IV.
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ABSTRACT: Terminally differentiated rhabdomyoblasts are common after or during therapy for rhabdomyosarcoma (RMS). Case reports have suggested that their presence after therapy does not indicate a poor prognosis, but significance and relationship to outcome has not been systematically studied. Management of patients with this finding can cause confusion. Slides and pathology reports from 44 patients with bladder/prostate RMS treated on Fourth Intergroup Rhabdomyosarcoma Study were examined by a pathologist experienced in RMS, and findings compared with institutional reports. Details regarding patient characteristics, outcome, and management were reviewed. Outcome of patients with various pathologic findings was assessed. One of 10 patients with only mature rhabdomyoblasts at their last procedure recurred, versus 4 of 17 patients with viable tumor and 2 of 17 patients with no viable tumor and no rhabdomyoblasts. Sixteen of 42 cases reviewed had results differing from our review. Mature rhabdomyoblasts are a discrete entity which may not be predictive of recurrence, but should be evaluated by a pathologist experienced with this entity. The presence of mature rhabdomyoblasts at the end of therapy for bladder/prostate RMS does not justify radical surgery. Sequential biopsies are subject to sampling error and should only be performed in the context of protocol-directed therapy to avoid unnecessary radical surgeries.Journal of Pediatric Hematology/Oncology 10/2006; 28(9):563-7. · 1.16 Impact Factor -
Article: Childhood rhabdomyosarcoma.
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ABSTRACT: A malignant tumor of striated muscle origin, Rhabdomyosarcoma (RMS) is a childhood tumor that has benefited from nearly 30 years of multimodality therapy culminating in a greater than 70% overall current 5-year survival. Prognosis for RMS is dependent on anatomic primary tumor site, age, completeness of resection, presence and number of metastatic sites, histology, and biology of the tumor cells. Multimodality treatment is based on risk stratification according to pretreatment stage, postoperative group, histology, and site. Therefore, pretreatment staging is vital for assessment and is dependent on primary tumor site, size, regional lymph node status, and presence of metastases. Unique to RMS is the concept of postoperative clinical grouping that assesses the completeness of disease resection and takes into account lymph node evaluation both at the regional and metastatic basins. At all sites, if operative resection of all disease is accomplished, including microscopic disease, survival is improved. Therefore, the surgeon plays a vital role in determining risk stratification for treatment and local control of the primary tumor for RMS. The current state of the art treatment is based on treatment protocols developed by the Soft Tissue Sarcoma Committee of the Children's Oncology Group.Seminars in Pediatric Surgery 03/2006; 15(1):57-62. · 2.93 Impact Factor -
Article: Primary hyperparathyroidism in pediatric patients.
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ABSTRACT: Primary hyperparathyroidism (HPT) is unusual in children. We reviewed our experience with HPT to better characterize these children. The retrospective review of patients <19 years old who underwent parathyroid resection for primary HPT from 1970 to 2000 was performed at a single institution.. Fifty-two patients were identified. Median age was 16.8 years (range: 4-18.9) with a female-to-male ratio of 3:2. Eighty-five percent had an elevated parathyroid hormone (PTH) level, and 15% had an inappropriately normal PTH level during hypercalcemia. Serum calcium was elevated in all patients except for 2 with multiple endocrine neoplasma (MEN)-IIA and 1 with familial non-MEN HPT, but both had elevated PTH levels. Alkaline phosphatase levels were significantly higher in children with documented bone involvement. At presentation 41 patients (79%) were symptomatic and end-organ damage (nephrocalcinosis, nephrolithiasis, acute pancreatitis, or bone involvement) occurred in 23 patients (44%). Thirty-four patients (65%) had a single adenoma; hyperplasia was identified in 16 patients (27%), and of these cases, 57% occurred in patients diagnosed with MEN-I. Short-term complications included transient hypocalcemia in 29 patients (56%) and transient vocal cord paralysis in 2 patients (4%). Long-term complications were significant for permanent hypocalcemia in 2 patients (4%) and no recurrent laryngeal nerve injuries. No parathyroid abnormalities were identified during exploration in 4 (8%) children. Long-term follow-up was achieved in 98% of patients for a mean and median of 13 years. Resolution of hypercalcemia was achieved in 94% of cases. The diagnosis of primary HPT in pediatric patients is frequently delayed, is commonly symptomatic, and has significant morbidity. For children in whom HPT is suspected, evaluation of serum calcium and PTH levels is diagnostic in 100% of children. Parathyroid resection is effective at restoring normal serum calcium, has few complications, and is the treatment of choice for children with primary hyperparathyroidism.PEDIATRICS 04/2005; 115(4):974-80. · 4.47 Impact Factor -
Article: Characteristics and outcomes of rhabdomyosarcoma patients with isolated lung metastases from IRS-IV.
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ABSTRACT: To better understand outcomes in children with rhabdomyosarcoma (RMS) and lung-only metastatic disease, the authors reviewed the experience from Intergroup Rhabdomyosarcoma Studies IV Pilot and IV. Patients with lung-only (n = 46) vs other sites of metastatic disease (n = 234) were reviewed using patient charts and the database of Children's Oncology Group (COG). Sixteen percent of patients with RMS and metastatic disease had isolated lung metastases. Thirty-one (67%) had more than 5 metastatic lung lesions. These were bilateral in 34 (74%). Only 6 patients were biopsied at diagnosis. Sixteen children (35%) did not receive any lung radiotherapy. Patients that received lung radiotherapy had fewer lung recurrences ( P = .04), although this has no significant impact on overall survival (OAS, 47% radiotherapy vs 31% no radiotherapy). Compared with patients with other sites of metastatic disease, patients with lung-only metastases have a greater proportion of favorable histology (67% vs 39%, P = .0017), negative nodal involvement (67% vs 32%, P = .0013), and parameningeal primaries (39% vs 12%) and a smaller proportion of extremity primaries (20% vs 33%, P = .0005 for site of primary tumor). Overall survival at 4 years for lung-only metastases was not significantly different from other single-site metastasis (42% vs 34%). Survival was not improved for unilateral disease or fewer than 5 metastatic lesions. Factors associated with diminished OAS include unfavorable histology (P = .0001) and age >10 years (P = .015). Children with RMS and lung-only metastases usually present with extensive bilateral disease that is frequently not biopsied nor given protocol-recommended radiotherapy (XRT). However, outcome is comparable, although slightly better, than patients with other single-site metastasis.Journal of Pediatric Surgery 01/2005; 40(1):256-62. · 1.45 Impact Factor -
Article: Does bladder preservation (as a surgical principle) lead to retaining bladder function in bladder/prostate rhabdomyosarcoma? Results from intergroup rhabdomyosarcoma study iv.
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ABSTRACT: We determine patient and tumor characteristics, event-free and overall survival, methods of local control, rate of bladder preservation and proportion with normal bladder function for patients with localized bladder/prostate (BP) rhabdomyosarcoma (RMS) treated on the Fourth Intergroup Rhabdomyosarcoma Study (IRS IV). We reviewed the records of 90 patients with nonmetastatic BP RMS enrolled on IRS IV for presenting characteristics, details of therapy and outcome. Of the 90 records 88 had sufficient information for review. Patient age distribution was less than 1 year for 7 patients, 1 to 9 years for 71 and 10 or greater years for 10. Tumors commonly arose in the bladder (70%), had favorable histology (embryonal or botryoid 80%), large (69% greater than 5 cm), unresectable (84% group III) and invasive (56% T2). Local therapy included radiation in 74 patients, and most patients underwent second-look operations after radiation. All patients received alkylating based chemotherapy. With a median followup of 6.1 years there have been 3 second malignancies, 1 toxic death and 18 relapses, for an event-free survival rate of 77%. Bladders were retained without relapse at last contact in 55 patients. Of those 55 patients 36 and of the entire group 40% had normal function determined by history. Of patients with nonmetastatic BP RMS on IRS IV 82% survived 6 years. Bladder function was preserved in 55% (36/66) of event-free survivors. Of all patients entered on study 40% (36 of 88) survive event-free with apparently normal functioning bladders. More precise long-term evaluation of bladder and sexual function will require application of better tools such as urodynamic studies and validated patient surveys.The Journal of Urology 07/2004; 171(6 Pt 1):2396-403. · 3.75 Impact Factor -
Article: Chronic intestinal pseudoobstruction associated with altered interstitial cells of cajal networks.
Journal of Pediatric Gastroenterology and Nutrition 05/2003; 36(4):492-7. · 2.30 Impact Factor
Top co-authors
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2006
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Childrens Hospital of Pittsburgh
Pittsburgh, PA, USA
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2005
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Mayo Clinic - Rochester
Rochester, MN, USA
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