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Biomedical subjects

Gerald M Haase

Publications and source records attributed to Gerald M Haase.

14 recordsLinked to original sources
PubMed2007

Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Antibiotics, Antineoplastic↗
PubMed2006

Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study.

PURPOSE: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗
PubMed2006

Radiation therapy for favorable histology Wilms tumor: prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4.

PURPOSE: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗
PubMed2006

Bilateral Wilms' tumors with progressive or nonresponsive disease.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Chemotherapy, Adjuvant↗
PubMed2005

Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group.

PURPOSE: 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). PATIENTS AND METHODS: 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). CONCLUSION: 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.

Child↗
PubMed2005

Quality assessment for Wilms' tumor: a report from the National Wilms' Tumor Study-5.

BACKGROUND/PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Abdominal Cavity↗
PubMed2004

Doxorubicin for favorable histology, Stage II-III Wilms tumor: results from the National Wilms Tumor Studies.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Adolescent↗
PubMed2004

Prophylactic urokinase in the management of long-term venous access devices in children: a Children's Oncology Group study.

PURPOSE: Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy. Since routine fibrinolytic therapy may decrease these complications, the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with standard heparin flushes in reducing the incidence of device-related infections and occlusions. MATERIALS AND METHODS: This study was a prospective, randomized phase III multicenter trial conducted by the Children's Cancer Group, in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months. Study end points were time to first occlusion or time to first device-related infection. RESULTS: Five hundred seventy-seven patients from 29 institutions were enrolled, of whom 51% had external catheters and 49% had ports. Urokinase administration resulted in fewer occlusive events than heparin (23% v 31%; P =.02), a longer time to first occlusive event (log-rank analysis, P =.006), and a 1.6-fold difference in the rate of occlusive events (Poisson regression, P =.003). Similar results were noted when comparing ports and tunneled catheters. The urokinase group also had a 1.4-fold difference in the rate of infection (Poisson regression, P =.05) and longer time to first infection (log-rank, P =.07), but the difference was significant only in tunneled catheters. CONCLUSION: Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration.

Adolescent↗
PubMed2004

Effect of duration of treatment on treatment outcome for patients with clear-cell sarcoma of the kidney: a report from the National Wilms' Tumor Study Group.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Adolescent↗
PubMed2004

Efficacy of complete resection for high-risk neuroblastoma: a Children's Cancer Group study.

BACKGROUND/PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Management of Wilms' tumour: current practice and future goals.

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.

Child↗
PubMed2003

Impact of radiotherapy for high-risk neuroblastoma: a Children's Cancer Group study.

PURPOSE: To assess the effect of local radiation administered to primary disease sites in children with high-risk neuroblastoma. MATERIALS AND METHODS: A total of 539 eligible patients were entered on protocol CCG-3891, consisting of chemotherapy, primary surgery, and 10 Gy of external beam radiation therapy (EBRT) to gross residual disease, followed by randomized assignment to continuation chemotherapy (CC) or autologous bone marrow transplantation (ABMT). ABMT patients received total body irradiation (TBI). RESULTS: Estimated event-free survival and overall survival at 5 years were 25% +/- 2% and 35% +/- 2%, respectively. Estimated 5-year locoregional recurrence rates were 51% +/- 5% and 33% +/- 7% for CC and ABMT patients (p = 0.004). For patients who received 10 Gy of EBRT to the primary, the addition of 10 Gy of TBI and ABMT decreased local recurrence compared with CC (22% +/- 12% and 52% +/- 8%, p = 0.022). EBRT did not increase acute toxicity, except for increased total parenteral nutrition administration. CONCLUSIONS: In combination with EBRT to the primary tumor site, the addition of 10 Gy of TBI as a component of high-dose chemotherapy with ABMT improved local control compared with CC without TBI. Results suggest a dose-response relationship for local EBRT. Short-term toxicity of local EBRT is limited.

Adolescent↗