G M Haase

Boston Children's Hospital, Boston, Massachusetts, United States

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Publications (95)591.42 Total impact

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    ABSTRACT: To provide guidelines for future trials, we reviewed the outcomes of children with synchronous bilateral Wilms tumors (BWT) treated on National Wilms Tumor Study-4 (NWTS-4). NWTS-4 enrolled 3335 patients including 188 patients with BWT (5.6%). Treatment and outcome data were collected. Among 188 BWT patients registered with NWTS-4, 195 kidneys in 123 patients had initial open biopsy, 44 kidneys in 31 patients had needle biopsies. Although pre-resection chemotherapy was recommended, 87 kidneys in 83 patients were managed with primary resection: Complete nephrectomy 48 in 48 patients, 31 partial/wedge nephrectomies in 27 patients, enucleations 8 in 8 patients. No initial surgery was performed in 45 kidneys in 43 patients, 5 kidneys in 3 patients not coded. Anaplasia was diagnosed after completion of the initial course of chemotherapy in 14 patients (initial surgical procedure: 9 open biopsies, 4 needle biopsies, 1 partial nephrectomy). The average number of days from the start of chemotherapy to diagnosis of anaplasia was 390 (range 44-1925 days). Relapse or progression of disease occurred in 54 children. End stage renal failure occurred in 23 children, 6 of whom had bilateral nephrectomies. The 8 year event free survival for BWT with favorable histology was 74%, and overall survival was 89%; whereas the event free survival for BWT with unfavorable histology was 40%, overall survival was 45%. The current analysis of patients with BWT treated on NWTS-4 shows that preservation of renal parenchyma is possible in many patients after initial preoperative chemotherapy. The incidence of end-stage renal disease remains significantly higher in children with BWT. Future studies are warranted to address the need for earlier biopsy in nonresponsive tumors and earlier definitive surgery to recognize unfavorable histology in these high-risk patients.
    Annals of surgery 03/2011; 253(5):1004-10. · 7.90 Impact Factor
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    ABSTRACT: There are no published reports on the optimal management and survival rates of children with Wilms tumor (WT) and peritoneal implants (PIs). Among favorable histology WT patients enrolled in the National Wilms Tumor Study (NWTS)-4 and NWTS-5, 57 children had PIs at the time of nephrectomy. The median age was 3 years 5 months (range, 3 months to 14 years). The majority of children (42 of 57 [74%)] had Stage III tumors; 15 had Stage IV disease. All patients received multimodality therapy. Of 56 children who underwent primary surgery, 48 (84%) had gross total resection of all tumors. All patients received 3-drug chemotherapy with vincristine, dactinomycin, and doxorubicin. Whole-abdomen radiotherapy (RT) was used in 47 patients (82%), and in 50 patients (88%) the RT dose was 10.5 Gy. After a median follow-up of 7.5 years, the overall abdominal and systemic tumor control rates were 97% and 93%, respectively. A comparative analysis between children with PIs and those without PIs showed no significant differences in the clinical characteristics between the two groups. The 5-year event-free survival rates with and without PIs were 90% (95% confidence interval, 78-96%) and 83% (95% confidence interval, 81-85%) respectively (p = 0.20). Multimodality therapy with surgery, whole-abdomen RT, and three-drug chemotherapy delivered according to the NWTS-4 and -5 protocols resulted in excellent abdominal and systemic tumor control rates. All children should be monitored in long-term surveillance programs for the early detection and management of therapy-related toxicities.
    International journal of radiation oncology, biology, physics 06/2010; 77(2):554-8. · 4.59 Impact Factor
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    ABSTRACT: To determine the event-free survival (EFS) and overall survival (OS) of children with very low risk Wilms tumor (VLRWT) treated with surgery only. Previous studies suggested that postoperative chemotherapy had not improved the prognosis of children with VLRWT. A total of 77 children <24 months of age with small (<550 g) Stage I favorable histology Wilms tumors were treated with surgery only. This study was closed based on stopping rules to ensure that the 2-year EFS was > or =90%. A total of 77 children were assessed for EFS and OS. Of these patients, 21 enrolled at the time of closure were recalled, treated with dactinomycin and vincristine (regimen EE4A), and censored for analysis thereafter. About 111 children subsequently treated with EE4A were available for comparison. Median follow-up of surviving patients was 8.2 years for surgery only (range, 1.9-11.8 years) and 5.2 years for the EE4A group (range, 1.6-8.9 years). The estimated 5-year EFS for surgery only was 84% (95% confidence interval [CI]: 73%, 91%); for the EE4A patients it was 97% (95% CI: 92%, 99%, P = 0.002). One death was observed in each treatment group. The estimated 5-year OS was 98% (95% CI: 87%, 99%) for surgery only and 99% (95% CI: 94%, 99%) for EE4A (P = 0.70). The surgery-only EFS was lower than anticipated but, coupled with a much higher than anticipated salvage rate of the chemotherapy naive patients whose disease recurred, led to an observed long-term OS equivalent to that seen with 2-drug chemotherapy. This approach to the treatment of patients with VLRWT eliminates the toxic side-effects of chemotherapy for a large majority of patients. A follow-up study is underway to confirm these findings.
    Annals of surgery 02/2010; 251(3):555-8. · 7.90 Impact Factor
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    ABSTRACT: We undertook this study to determine (1) the frequency with which spilled tumor cells of favorable histology produced intra-abdominal disease in patients treated with differing chemotherapy regimens and abdominal radiation therapy (RT) and (2) the patterns of relapse and outcomes in such patients. The influence of RT dose (0, 10, and 20 Gy), RT fields (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2 drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence rates was analyzed by logistic regression in 450 patients. Each patient was considered at risk for two types of failure: flank and subdiaphragmatic beyond-flank recurrence, with the correlation between the two outcomes accounted for in the analyses. The crude odds ratio for the risk of recurrence relative to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates with and without spillage, respectively, were 79% and 87% for relapse-free survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04). Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor spillage. Tumor spillage in Stage II patients reduced relapse-free survival and overall survival, but only the latter was of statistical significance. These data provide a basis for assessing the risks vs. benefits when considering treatment for children with favorable histology Wilms tumor and surgical spillage.
    International journal of radiation oncology, biology, physics 05/2009; 76(1):201-6. · 4.59 Impact Factor
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    ABSTRACT: Extension of Wilms' tumor into the ureter is a rare event. We reviewed the National Wilms' Tumor Study Group (NWTSG) database to define the clinical presentation, associated pathologic features, and clinical outcome of these patients. Records of children identified to have ureteral extension of Wilms' tumor enrolled in NWTS-3, 4, and 5 were reviewed. Presenting symptoms, diagnostic studies, histopathologic findings, operation performed, and outcome were recorded. The NWTS-5 surgical data were prospectively collected as part of the quality assurance program. Forty-five children were identified with ureteral extension. For NWTS-5, the incidence of ureteral extension was 2%. Clinical presentations were gross hematuria in 22 patients, 2 had passage of tissue per urethra, and 1 child had a urethral mass. The remainder had nonspecific presentations. Ureteral extension was seen on preoperative imaging in 14 patients, intraoperatively in 22, and on pathologic examination in 9 patients. Hydronephrosis was noted in 12 patients, and there was nonfunction of the kidney in another 8. Laterality of the tumor was right side in 26 and left in 19. Cystoscopy was performed in 12 children. Findings included tumor seen at the ureteral orifice in 6 patients and bleeding from the orifice in one child. All patients had radical nephrectomy including partial ureterectomy. The ureteral margin was positive in 3 patients, including 2 of the 7 with separate removal of the ureteral extension. The number of patients in each clinical stage was as follows: stage I, 10; stage II, 18; stage III, 14; and stage IV, 3. The tumor extended into the proximal ureter in 23 patients, distal ureter in 13, 7 had extension into the bladder, and 1 had urethral involvement. The level of ureteral extension was not clearly noted in the 45th child. The median follow-up was 96 months. Overall, 41 of 45 patients were alive at last contact. There were 3 deaths because of tumor in patients with unfavorable histologic tumors, and 1 because of treatment toxicity in a child with favorable histologic findings. Ureteral extension occurs in approximately 2% of patients with Wilms' tumor. The diagnosis should be suspected in patients with gross hematuria, hydronephrosis, or nonfunctioning kidney. Cystoscopy with retrograde ureterogram may aid in preoperative diagnosis in these patients. Preoperative diagnosis is important because complete resection of the involved portion of ureter at the time of nephrectomy can avoid residual disease and the need for second surgery or radiation therapy.
    Journal of Pediatric Surgery 10/2008; 43(9):1625-9. · 1.38 Impact Factor
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    ABSTRACT: We evaluated the use of alternating cycles of cyclophosphamide/etoposide and carboplatin/etoposide in children entered on National Wilms Tumor Study (NWTS)-5 who were diagnosed between August 1, 1995 and May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D, and doxorubicin (VAD) and radiation therapy (DD-4A). One hundred three patients who relapsed or had progressive disease after initial VAD chemotherapy and radiation therapy were registered on stratum C of the NWTS-5 Relapse protocol. Twelve patients were not evaluable: five due to insufficient data, six due to major protocol violations, and one for refusal of therapy. Among the 91 remaining patients, 14 with stage V Wilms tumor (WT), 1 with contralateral relapse, and 16 who did not achieve a complete response (CR) to the initial three-drug chemotherapy were not included in this analysis. Relapse treatment included alternating courses of the drug pairs cyclophosphamide/etoposide and carboplatin/etoposide, surgery, and radiation therapy. The outcomes of 60 patients were analyzed. The lung was the only site of relapse for 33 patients; other sites of relapse included the operative bed, the abdomen, and liver. Four-year event-free survival (EFS) and overall survival (OS) were 42.3 and 48.0% respectively for all patients and were 48.9 and 52.8% for those who relapsed in the lungs only. Thrombocytopenia was the most frequent toxicity. These results demonstrate that approximately one-half of children with unilateral WT who relapse after initial treatment with VAD and radiation therapy can be successfully retreated.
    Pediatric Blood & Cancer 03/2008; 50(2):236-41. · 2.35 Impact Factor
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    ABSTRACT: NWTS-5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. Seventy-two patients who relapsed after immediate nephrectomy (stages I and II), initial chemotherapy with vincristine (VCR) and actinomycin D and no radiation therapy were registered on stratum B of the NWTS-5 relapse protocol. Four patients were not evaluable: one due to insufficient data and three due to major protocol violations. Among the 68 remaining patients, one who was 19 years of age at initial diagnosis of Wilms tumor, five with bilateral Wilms tumor at diagnosis, three who developed a contralateral relapse, and one with persistent disease were not included in this analysis. Relapse treatment included surgical excision, when feasible, radiation therapy and alternating courses of VCR, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. The outcomes of 58 patients were analyzed. The lung was the only site of relapse for 31 patients. Event-free survival 4 years after relapse was 71.1% and 4-year overall survival was 81.8% for all patients and were 67.8 and 81.0% for those who relapsed only to their lungs. The most frequent toxicities were hematological. These results demonstrate that a significant proportion of children with Wilms tumor who relapse after initial treatment with VCR and actinomycin D can be successfully re-treated.
    Pediatric Blood & Cancer 06/2007; 48(5):493-9. · 2.35 Impact Factor
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    ABSTRACT: An objective of the fifth National Wilms' Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms' tumor (AH). Prospective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation. A total of 2,596 patients with Wilms' tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively. The prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.
    Journal of Clinical Oncology 06/2006; 24(15):2352-8. · 18.04 Impact Factor
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    ABSTRACT: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend = 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes.
    International Journal of Radiation OncologyBiologyPhysics 06/2006; 65(1):203-9. · 4.52 Impact Factor
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    ABSTRACT: To provide guidelines for future cooperative group trials, we reviewed the outcomes of children with bilateral Wilms' tumors (BWTs) treated on National Wilms Tumor Study-4 (NWTS-4) who had progressive or nonresponsive disease (PNRD). NWTS-4 enrolled 3335 patients from August 1986 to September 1994 including 188 patients with BWT (5.6%). Treatment and outcome data were collected on patients with BWT. Treatment guidelines were outlined in the protocol, but patients were not on study. Thirty-eight children with BWT had PNRD. Preoperative chemotherapy was given for a median of 7 months (range, 2-29 months) before definitive resection. After the initial chemotherapy regimen, 36 children went on to a second regimen, and of these, 21 children received a third regimen before resection. Eleven patients received irradiation to one or both kidneys. Pathology at resection revealed previously undiagnosed anaplasia in 3 patients (2 diffuse and 1 focal) treated for 14, 15, and 15 months before resection. A fourth patient developed a diffusely anaplastic tumor 13 months after therapy. Other pathological findings included rhabdomyomatous (4 patients) or differentiated stromal elements (10 patients) and complete necrosis (1 patient). Ten kidneys from 7 patients lacked biopsy at presentation or pathology review of those specimens. BWT patients with PNRD received prolonged courses of chemotherapy. Early and sequential biopsies to establish the reason for failure to respond should be obtained. This will identify anaplastic tumors managed best by early nephrectomy and intensive chemotherapy and will also distinguish differentiated tumors that are best managed with early resection, but less intensive therapy after nephrectomy.
    Journal of Pediatric Surgery 05/2006; 41(4):652-7; discussion 652-7. · 1.38 Impact Factor
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    ABSTRACT: Computed tomography (CT) of the chest with its increased sensitivity frequently identifies lesions not visible on chest radiograph. Treatment of such lesions is controversial. A recent review suggests that patients with Wilms' tumor with pulmonary lesions detected only by CT, who were treated with dactinomycin and vincristine, have an inferior outcome compared with those who also received pulmonary radiation therapy (RT) and doxorubicin. It is important to determine if these small lesions seen only on CT represent metastatic disease and whether patients with these lesions require RT and/or doxorubicin for optimal outcome. Patients with Wilms' tumor with lung metastasis, registered on National Wilms' Tumor Study 5, were reviewed, and those with CT-only lesions who had a radiology and surgical checklist submitted were identified. The treatment regimens of these patients and the histological findings of the pulmonary lesions are presented. We analyzed the pathological findings by whether the patients had single or multiple lesions. Of 2498 patients registered on National Wilms' Tumor Study 5, 252 had pulmonary metastases. Of these patients, 129 (5.2%) had CT-only lesions (<1 cm). Forty-two of these patients (20 boys and 22 girls) underwent lung biopsy at the discretion of the attending physicians. The local tumor stages in these patients were stage I (7%), II (34%), and III (59%). The treatment stages in these patients were stage I (n = 3, 2 drugs), II (n = 3, 2 drugs), III (n = 12, 3 drugs); and IV (n = 24, 3 drugs + RT). There were 16 patients with isolated lung lesions and 26 with multiple lesions, average size 5.8 +/- 0.5 mm. Of 16 isolated lesions, 13 patients (82%) and 69% (18/26) with multiple lesions had tumor on biopsy. Of the 24 who received RT, 8 had a negative biopsy and, thus, may not have needed the RT. Five of 6 treated with just 2 drugs may have been undertreated. Nine of 12 treated with 3 drugs had tumor on biopsy. Computed tomography-only pulmonary lesions are not invariably tumor, demonstrating the need for histopathological confirmation. Biopsy remains critical until radiographic techniques allow differentiation between benign and malignant lesions to optimally direct therapy.
    Journal of Pediatric Surgery 02/2006; 41(1):162-7; discussion 162-7. · 1.38 Impact Factor
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    ABSTRACT: In children undergoing nephrectomy for Wilms tumor exploration of the contralateral kidney has been recommended to detect occult tumors missed on preoperative evaluation. In this review of the National Wilms Tumor Study (NWTS) 4 cases of bilateral Wilms tumors (BWT) we evaluate incidence and outcome of missed bilateral lesions. NWTS-4 enrolled 3,335 patients from August 1986 through September 1994. There were 188 patients with BWT or 5.6% of the total registered. The operative records, pathology and imaging reports were reviewed. In 11 cases synchronous BWT was diagnosed at surgical exploration, which represents 5.9% of the bilateral cases but only 0.3% of all NWTS-4 cases. Two patients did not undergo preoperative imaging and were excluded from analysis. The size of the missed lesions was less than 1 cm in 6 patients and 1 to 2 cm in 3. Computerized tomography was performed in all patients except one who entered early in the study. Management of missed lesions included enucleation in 2 cases, biopsy in 6 and no surgery in 1. No patient underwent irradiation. The postoperative chemotherapy regimen consisted of doxorubicin, dactinomycin and vincristine in 6 children, and dactinomycin and vincristine in 3. Median followup was 9 years. There were no recurrences in any kidney with a missed lesion. All 9 patients were alive and disease-free at last followup. Routine contralateral renal exploration will identify few occult tumors not detected on preoperative imaging. Omission of routine exploration will not likely affect the outcome or management of newly diagnosed Wilms tumor provided preoperative computerized tomography or magnetic resonance imaging is performed. The outcome in these patients was excellent.
    The Journal of Urology 11/2005; 174(4 Pt 2):1519-21; discussion 1521. · 3.70 Impact Factor
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    ABSTRACT: To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. ResultsLOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.
    Journal of Clinical Oncology 11/2005; 23(29):7312-21. · 18.04 Impact Factor
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    ABSTRACT: Surgical technique impacts both local tumor stage and risk of local recurrence in Wilms' tumor. A surgical quality assurance program was part of National Wilms' Tumor Study-5 to assess protocol compliance. Surgical checklists, operative, and pathology reports were reviewed concurrently to arrive at the final local tumor stage. If a protocol violation occurred, a letter was sent to the responsible surgeon. Tumor laterality, extent, type of resection, contralateral exploration, node involvement, spills, and local recurrence were reviewed. Relative risk and logistic regression analyses were performed. There were 1305 nephrectomies. Lymph node sampling was not performed in 117 (9%) patients: stage I, 41 (11.5%), stage II, 57 (12%), and stage III, 19 (4%). Of importance, 41% (187/457) of stage III cases were designated stage III solely on the basis of positive lymph nodes. Tumor spill occurred in 19.3% (253/1305) of children. Fifty-four local spills were in stage II tumors and 97 in stage III. Diffuse spill occurred in 102 patients with stage III tumors. Seventeen preoperative and 13 intraoperative biopsies were performed. Intraoperative tumor rupture was the most common cause of tumor spill accounting for 139 (55%) spills. Nineteen (7.5%) children were upstaged, receiving more intensive therapy because of spill. Included in the group were 3 of 17 preoperative biopsies and 5 of 13 intraoperative biopsies. Spills (13/253) were determined to be avoidable. Eight were biopsies, 5 because tumor was transected in the renal vein (4) or ureter (1). In stage II patients where lymph nodes were not sampled, there is an increase in local relapse rate that did not achieve statistical significance because of the small number of events. Although most surgeons complied with the surgical guidelines, numerous deviations were identified including failure to sample lymph nodes (117 cases) and unnecessary biopsies leading to tumor spill (30 cases). Protocol violations have an adverse impact on tumor staging, potentially increasing the risk for local tumor recurrence or intensity and toxicity of therapy.
    Journal of Pediatric Surgery 02/2005; 40(1):208-12; discussion 212-3. · 1.38 Impact Factor
  • International Journal of Radiation Oncology Biology Physics - INT J RADIAT ONCOL BIOL PHYS. 01/2005; 63.
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    ABSTRACT: After randomized trials in the 1980s, doxorubicin (DOX) was added to dactinomycin plus vincristine as standard chemotherapy for patients who had Stage III Wilms tumor (WT) of favorable histology (FH). Double-agent chemotherapy was retained for patients with Stage II disease. In this study, the authors reevaluated the efficacy of DOX using extended follow-up and additional patients. The relative risks (RR) (DOX vs. no DOX) of disease recurrence and mortality were estimated for patients with Stage II-III/FH WT who were enrolled in the third and fourth National Wilms Tumor Studies (NWTS-3 and NWTS-4). The risk of congestive heart failure (CHF) was estimated for all patients who received DOX. No statistically significant effects of DOX were found for patients with Stage II tumors. For patients with Stage III tumors, the 8 year recurrence-free survival (RFS) and overall survival (OS) rates for randomized patients on NWTS-3 were 84% and 89%, respectively, for patients who received DOX (n = 130) and 74% and 83%, respectively, for patients who did not receive DOX (n = 118). Including all patients with Stage III disease who received DOX (n = 678) and did not receive DOX (n = 138), the RRs of recurrence were 0.47 (P = 0.007) and 0.40 (P = 0.011), and local recurrence respectively, after adjustment for radiation therapy (RT) dose, whereas the RR of mortality adjusted for RT and study was 0.68 (P = 0.17). The 20-year risk of CHF after primary DOX treatment on NWTS-3 and NWTS-4 was 1.2%. The inclusion of data from nonrandomized patients yielded estimates of DOX treatment effects for Stage III/FH WT that were stronger, albeit more susceptible to bias, than reported previously. Despite a lower reported risk of CHF, conclusive evidence that frontline therapy with DOX definitively improves survival remains elusive.
    Cancer 10/2004; 101(5):1072-80. · 5.20 Impact Factor
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    ABSTRACT: Thin films of silicon nitride (SiN) or silicon carbonitride (SiCN) were deposited as liners at metal-1 in a dual level metal Cu/organosilicate glass interconnect. Breakdown field and time dependent dielectric breakdown lifetime testing of comb/serpent test structures with SiN or SiCN liners showed improvements in performance, relative to a baseline no liner split. Two dimensional electric field simulations demonstrated that the dielectric liner significantly reduced the electric field at the Cu/OSG/etch stop interface.
    Interconnect Technology Conference, 2004. Proceedings of the IEEE 2004 International; 07/2004
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    ABSTRACT: Previous reports indicate that complete resection of high-risk neuroblastoma improves outcome but may entail high surgical complication rates. The authors evaluated the effect of complete primary site resection on event-free survival (EFS), overall survival (OS), and complication rates in patients entered on a high-risk neuroblastoma treatment protocol. A total of 539 eligible patients with high-risk neuroblastoma were entered on protocol CCG-3891. Patients were assigned randomly to continuation chemotherapy or autologous bone marrow transplantation. Surgical resection was performed at diagnosis or after induction chemotherapy. Surgeons assessed resection as complete (CR), minimal residual (<5%, MR), or partial (PR). Incomplete resections received secondary resection or 10 Gy of external beam radiation. Patients were evaluated for EFS, OS, and complications of surgery based on completeness of overall best resection. The proportion of patients resectable at diagnosis was 27% for CR and 14% for MR. This improved after chemotherapy to 45% and 25%. Complication rates based on completeness of resection were 29%, 38%, and 36% for CR, MR, and PR, respectively. Estimated 5-year EFS rate was 30% +/- 3% for patients who achieved CR (n = 210) compared with 25% +/- 3% (P =.1010) for those with less than CR (n = 258). Resectability improved after neoadjuvant chemotherapy. Complete resection did not increase complications. There was a small survival benefit for complete resection. This study suggests that complete resection may still be important in the current era of intense chemotherapy and transplant.
    Journal of Pediatric Surgery 06/2004; 39(6):931-6. · 1.38 Impact Factor
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    ABSTRACT: Most patients with Wilms' tumour in Europe and North America can be cured with treatment and subsequently lead a normal adulthood. However, for some, therapy as applied today results in long-term side-effects and creates a substantial burden on quality of life. Therefore, investigators involved in the management of patients with Wilms' tumour are increasingly focusing their efforts on curtailing the long-term sequelae of therapy. This aim has been achieved by lowering the total amount of chemotherapy, radiotherapy, or both administered to patients who have characteristics associated with favourable outcome. Although excellent survival has been maintained, many patients receive less therapy today than patients with similar characteristics did a decade or two ago. Better understanding of the biological processes that lead to this childhood cancer will allow further improvements in its management.
    The Lancet Oncology 02/2004; 5(1):37-46. · 25.12 Impact Factor
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    ABSTRACT: To evaluate the effect of conventional and standard (ST) versus pulse-intensive (PI) chemotherapy and short-duration versus long-duration chemotherapy on relapse-free survival (RFS) and overall survival rates of patients with clear-cell sarcoma of the kidney (CCSK) entered onto the National Wilms' Tumor Study (NWTS)-4. The 5-year and 8-year RFS rates were determined for patients with CCSK treated on the NWTS-4. After August 6, 1986, 40 previously untreated children younger than 16 years with CCSK were randomly assigned, after the completion of 6 months of chemotherapy, to discontinue (short) or continue 9 additional months (long) of treatment with chemotherapy regimens that included vincristine and either divided-dose (ST) courses (5 days) or single-dose (PI) treatment with dactinomycin and divided-dose (ST) courses (3 days) or single-dose (PI) treatment with doxorubicin. For patients with CCSK, the 5- and 8-year RFS rates were 65.2% and 60.6%, respectively, for patients randomly assigned to the short chemotherapy and 87.8% (both 5- and 8-year RFS) for patients randomly assigned to the long chemotherapy (P =.08). The overall survival rates for patients at 5 and 8 years were 95.5% and 85.9%, respectively, for the short chemotherapy and 87.5% (both 5- and 8-year overall survival) for the long chemotherapy (P =.99). In NWTS-4, the overall survival rates for patients with CCSK improved from NWTS-3 (83% v 66.9% at 8 years, respectively; P <.01). CCSK patients exhibit an improved RFS from a longer course of therapy when using vincristine, doxorubicin, and dactinomycin, but their long-term survival is unchanged compared with patients receiving 6 months of therapy. The overall survival rates for patients with CCSK have improved from NWTS-3.
    Journal of Clinical Oncology 02/2004; 22(3):468-73. · 18.04 Impact Factor

Publication Stats

2k Citations
591.42 Total Impact Points

Institutions

  • 1988–2011
    • Boston Children's Hospital
      • Department of Pediatric Surgery
      Boston, Massachusetts, United States
    • Washington University in St. Louis
      San Luis, Missouri, United States
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 1988–2008
    • Children's Hospital Colorado
      Aurora, Colorado, United States
  • 2006
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
  • 2005–2006
    • University of Michigan
      • Department of Surgery
      Ann Arbor, MI, United States
  • 2004–2006
    • University of Washington Seattle
      • Department of Biostatistics
      Seattle, WA, United States
  • 1995–2006
    • University of Colorado
      • • Department of Surgery
      • • Division of Pediatric Surgery
      Denver, Colorado, United States
    • University of Houston
      Houston, Texas, United States
  • 1998–2005
    • Roswell Park Cancer Institute
      • Department of Pediatrics
      Buffalo, New York, United States
  • 2003–2004
    • The Children’s Medical Group
      Poughkeepsie, New York, United States
    • Northwestern University
      Evanston, Illinois, United States
  • 2000
    • University of Illinois at Chicago
      • Department of Pediatrics (Chicago)
      Chicago, IL, United States
  • 1989–1994
    • University of California, San Francisco
      • Department of Pediatrics
      San Francisco, CA, United States
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 1993
    • The Children's Hospital of Buffalo
      New York City, New York, United States
  • 1992
    • Wilford Hall Ambulatory Surgery Center
      Lackland Air Force Base, Texas, United States
    • Mayo Foundation for Medical Education and Research
      • Department of Urology
      Scottsdale, AZ, United States
  • 1990
    • Hospital of the University of Pennsylvania
      • Department of Radiation Oncology
      Philadelphia, Pennsylvania, United States