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Dive into the research topics where Robert C. Shamberger is active.

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Featured researches published by Robert C. Shamberger.


Journal of Clinical Oncology | 2009

Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study

Linda Granowetter; Richard B. Womer; Meenakshi Devidas; Mark Krailo; Chenguang Wang; Mark Bernstein; Neyssa Marina; Patrick J. Leavey; Mark C. Gebhardt; John H. Healey; Robert C. Shamberger; Allen M. Goorin; James S. Miser; James S. Meyer; Carola Arndt; Scott L. Sailer; Karen J. Marcus; Elizabeth J. Perlman; Paul W. Dickman; Holcombe E. Grier

PURPOSE The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. METHODS Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. RESULTS Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. CONCLUSION Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.


Annals of Surgery | 1999

Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4.

Robert C. Shamberger; K.A. Guthrie; Michael L. Ritchey; Gerald M. Haase; Janice R. Takashima; J. B. Beckwith; Giulio J. D'Angio; Daniel M. Green; Norman E. Breslow

OBJECTIVE To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence.


Journal of Clinical Oncology | 2006

High-Risk Neuroblastoma Treated With Tandem Autologous Peripheral-Blood Stem Cell–Supported Transplantation: Long-Term Survival Update

Rani E. George; Shuli Li; Cheryl Medeiros-Nancarrow; Donna Neuberg; Karen J. Marcus; Robert C. Shamberger; Michael A. Pulsipher; Stephan A. Grupp; Lisa Diller

PURPOSE To provide an update on long-term survival of patients with high-risk neuroblastoma treated with tandem cycles of myeloablative therapy and peripheral-blood stem-cell rescue (PBSCR). PATIENTS AND METHODS Ninety-seven patients with high-risk neuroblastoma were treated between 1994 and 2002. Patients underwent induction therapy with five cycles of standard agents, resection of the primary tumor and local radiation, and two consecutive courses of myeloablative therapy (including total-body irradiation) with PBSCR. RESULTS Fifty-one patients have experienced relapse or died. Median follow-up time among the 46 patients who remain alive without progression is 5.6 years (range, 15.1 months to 9.9 years). Progression-free survival (PFS) rate at 5 years from diagnosis was 47% (95% CI, 36% to 56%), and PFS rate at 7 years was 45% (95% CI, 34% to 55%). Overall survival rate was 60% (95% CI, 48% to 69%) and 53% (95% CI, 40% to 64%) at 5 and 7 years, respectively. The 5- and 7- year PFS rates from time of first transplantation for 82 patients who completed both transplants were 54% (95% CI, 42% to 64%) and 52% (95% CI, 40% to 63%), respectively. Five patients died from treatment-related toxicity after tandem transplantation. Relapse occurred in 37 (42%) of 89 patients, mainly within 3 years of transplantation and primarily in diffuse osseous sites. No primary CNS relapse or secondary leukemia was seen. One patient developed synovial cell sarcoma 8 years after therapy. CONCLUSION High-dose therapy with tandem autologous stem-cell rescue is effective for treating high-risk neuroblastoma, with encouraging long-term survival. CNS relapse and secondary malignancies are rare after this therapy.


Cancer | 1986

The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia

Robert C. Shamberger; Howard J. Weinstein; M J Delorey; Raphael H. Levey

The treatment of acute leukemia in childhood has been increasingly successful. Infectious complications are the major cause of morbidity and mortality among these patients receiving aggressive chemotherapy. In particular, neutropenic enterocolitis or typhlitis has had a reported mortality of 50% to 100%. The authors reviewed a series of 77 previously untreated patients with acute myelogenous leukemia begun on treatment from March 1976 to June of 1984 to better define the characteristics of typhlitis and its optimum management. Twenty‐five patients had episodes of typhlitis, characterized by fever, abdominal pain, and tenderness, occurring during periods of neutropenia. Ten of these patients had watery diarrhea as a major additional symptom, and nine patients had a significant episode of gastrointestinal bleeding. In seven instances, blood culture results were positive, all for intestinal flora. The episodes of typhlitis occurred most frequently during the induction therapy (19 patients). Five patients experienced typhlitis during maintenance therapy, and one patient had acute appendicitis. Two patients had typhlitis during their reinduction therapy, and of note, one had had abdominal symptoms during her initial induction. All patients were treated initially with broad‐spectrum antibiotics and bowel rest. Four criteria have been used for surgical intervention: (1) persistent gastrointestinal bleeding after resolution of neutropenia and thrombocytopenia and correction of clotting abnormalities; (2) evidence of free intraperitoneal perforation; (3) clinical deterioration requiring support with vasopressors, or large volumes of fluid, suggesting uncontrolled sepsis; and (4) development of symptoms of an intra‐abdominal process, in the absence of neutropenia, which would normally require surgery. Using these criteria, five patients required surgical intervention for typhlitis or its sequelae and one for acute appendicitis. There was one perioperative death resulting from miliary tuberculosis. Among the 21 patients managed medically, there was 1 death resulting from typhlitis in a patient in whom surgery was deferred because of her multiple failures to enter remission.


The American Journal of Gastroenterology | 2011

Consensus for Managing Acute Severe Ulcerative Colitis in Children: A Systematic Review and Joint Statement From ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN

Dan Turner; Simon Travis; Anne M. Griffiths; Frank M. Ruemmele; Arie Levine; Eric I. Benchimol; Marla Dubinsky; George Alex; Robert N. Baldassano; Jacob C. Langer; Robert C. Shamberger; Jeffrey S. Hyams; Salvatore Cucchiara; Athos Bousvaros; Johanna C. Escher; James Markowitz; David C. Wilson; Gert Van Assche; Richard K. Russell

OBJECTIVES:Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review of the literature and robust consensus process. This manuscript is a product of a joint effort of the ECCO (European Crohns and Colitis Organization), the Pediatric Porto Inflammatory Bowel Disease (IBD) Working group of ESPGHAN (European Society of Pediatric Gastroenterology, Hepatology, and Nutrition) and ESPGHAN.METHODS:A group of 19 experts in pediatric IBD participated in an iterative consensus process including two face-to-face meetings. A total of 17 predefined questions were addressed by working subgroups based on a systematic review of the literature.RESULTS:The recommendations and practice points were eventually endorsed with a consensus rate of at least 95% regarding: definitions, initial evaluation, standard therapy, timing of second-line therapy, the role of endoscopic evaluation and heparin prophylaxis, how to administer second-line medical therapy, how to assess response, surgical considerations, and discharge recommendations. A management flowchart is presented based on daily scoring of the Pediatric Ulcerative Colitis Activity Index (PUCAI), along with 28 formal recommendations and 34 practice points.CONCLUSIONS:These guidelines provide clinically useful points to guide the management of ASC in children. Taken together, the recommendations offer a standardized protocol that allows effective monitoring of disease progress and timely treatment escalation when needed.


The New England Journal of Medicine | 2010

Outcome after Reduced Chemotherapy for Intermediate-Risk Neuroblastoma

David Baker; Mary Lou Schmidt; Susan L. Cohn; John M. Maris; Wendy B. London; Allen Buxton; Daniel O. Stram; Robert P. Castleberry; Hiroyuki Shimada; Anthony D. Sandler; Robert C. Shamberger; A. Thomas Look; C. Patrick Reynolds; Robert C. Seeger; Katherine K. Matthay

BACKGROUND The survival rate among patients with intermediate-risk neuroblastoma who receive dose-intensive chemotherapy is excellent, but the survival rate among patients who receive reduced doses of chemotherapy for shorter periods of time is not known. METHODS We conducted a prospective, phase 3, nonrandomized trial to determine whether a 3-year estimated overall survival of more than 90% could be maintained with reductions in the duration of therapy and drug doses, using a tumor biology-based therapy assignment. Eligible patients had newly diagnosed, intermediate-risk neuroblastoma without MYCN amplification; these patients included infants (<365 days of age) who had stage 3 or 4 disease, children (≥365 days of age) who had stage 3 tumors with favorable histopathological features, and infants who had stage 4S disease with a diploid DNA index or unfavorable histopathological features. Patients who had disease with favorable histopathological features and hyperdiploidy were assigned to four cycles of chemotherapy, and those with an incomplete response or either unfavorable feature were assigned to eight cycles. RESULTS Between 1997 and 2005, a total of 479 eligible patients were enrolled in this trial (270 patients with stage 3 disease, 178 with stage 4 disease, and 31 with stage 4S disease). A total of 323 patients had tumors with favorable biologic features, and 141 had tumors with unfavorable biologic features. Ploidy, but not histopathological features, was significantly predictive of the outcome. Severe adverse events without disease progression occurred in 10 patients (2.1%), including secondary leukemia (in 3 patients), death from infection (in 3 patients), and death at surgery (in 4 patients). The 3-year estimate (±SE) of overall survival for the entire group was 96±1%, with an overall survival rate of 98±1% among patients who had tumors with favorable biologic features and 93±2% among patients who had tumors with unfavorable biologic features. CONCLUSIONS A very high rate of survival among patients with intermediate-risk neuroblastoma was achieved with a biologically based treatment assignment involving a substantially reduced duration of chemotherapy and reduced doses of chemotherapeutic agents as compared with the regimens used in earlier trials. These data provide support for further reduction in chemotherapy with more refined risk stratification. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003093.)


Journal of Pediatric Surgery | 1988

Surgical repair of pectus excavatum

Robert C. Shamberger; Kenneth J. Welch

From 1958 to March 1987 we corrected 704 patients with pectus excavatum. The condition occurred more frequently in boys (544 patients) than girls (160 patients). In the majority of patients (86%), the defect was evident at birth or within the first year of life. Musculoskeletal abnormalities were identified in 133 patients (scoliosis, 107; kyphosis, 4; myopathy, 3; Polands syndrome, 3; Marfans syndrome, 2; Pierre Robin syndrome, 2; prune belly syndrome, 2; neurofibromatosis, 3; cerebral palsy, 4; tuberous sclerosis, 1; and congenital diaphragmatic hernia, 2). Sixteen patients had associated congenital heart disease. A family history of chest wall deformity was present in 37% of the cases and a history of scoliosis in 11%. Surgical correction was performed using a uniform technique for bilateral subperichondrial resection of the deformed costal cartilages and sternal osteotomy resecting a wedge of the anterior cortex and fracturing the posterior cortex. Anterior displacement was maintained with silk sutures closing the osteotomy defect. In 28 early cases, the sternum was secured by intramedullary fixation with a Steinman pin. All repairs were completed with a low complication rate (4.4%; pneumothorax, 11; wound infection, 5; wound hematoma, 3; wound dehiscence, 5; pneumonia, 3; seroma, 1; hemoptysis, 1; hemopericardium, 1). Six complications were associated with Steinman pin fixation (hemoptysis, seroma, hemopericardium, pneumothorax, 3). Major recurrence occurred in 17 patients (2.7%) and led to revision in 12. Satisfactory long-term results were achieved in the remaining 687 patients, with follow-up ranging from 2 weeks to 27 years. Mean follow-up was 4.3 years.(ABSTRACT TRUNCATED AT 250 WORDS)


Journal of Clinical Oncology | 2001

Treatment With Nephrectomy Only for Small, Stage I/Favorable Histology Wilms’ Tumor: A Report From the National Wilms’ Tumor Study Group

Daniel M. Green; N. E. Breslow; J. B. Beckwith; M. L. Ritchey; Robert C. Shamberger; G. M. Haase; Giulio J. D'Angio; Elizabeth J. Perlman; M. Donaldson; P. E. Grundy; R. Weetman; M. J. Coppes; M. Malogolowkin; P. Shearer; P. Coccia; M. Kletzel; P. R M Thomas; R. Macklis; G. Tomlinson; V. Huff; R. Newbury; D. Weeks

PURPOSE Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.


Pediatrics | 2008

Surgical repair of pectus excavatum markedly improves body image and perceived ability for physical activity: multicenter study.

Robert E. Kelly; Thomas F. Cash; Robert C. Shamberger; Karen Mitchell; Robert B. Mellins; M. Louise Lawson; Keith T. Oldham; Richard G. Azizkhan; Andre Hebra; Donald Nuss; Michael J. Goretsky; Ronald J. Sharp; George Holcomb; Walton K.T. Shim; Stephen M. Megison; R. Lawrence Moss; Annie Fecteau; Paul M. Colombani; Traci Bagley; Amy Quinn; Alan B. Moskowitz

OBJECTIVE. This study evaluated changes in both physical and psychosocial quality of life reported by the parent and child after surgical repair of pectus excavatum. METHODS. As part of a multicenter study of pectus excavatum, a previously validated tool called the Pectus Excavatum Evaluation Questionnaire was administered by the research coordinator, via telephone, to parents and patients (8–21 years of age) before and 1 year after surgery. Eleven North American childrens hospitals participated. From 2001 to 2006, 264 patients and 291 parents completed the initial questionnaire, and 247 patients and 274 parents completed the postoperative questionnaire. Responses used a Likert-type scale of 1 to 4, reflecting the extent or frequency of a particular experience, with higher values conveying less-desirable experience. RESULTS. Preoperative psychosocial functioning was unrelated to objective pectus excavatum severity (computed tomographic index). Patients and their parents reported significant positive postoperative changes. Improvements occurred in both physical and psychosocial functioning, including less social self-consciousness and a more-favorable body image. For children, the body image component improved from 2.30 ± 0.62 (mean ± SD) to 1.40 ± 0.42 after surgery and the physical difficulties component improved from 2.11 ± 0.82 to 1.37 ± 0.44. For the parent questionnaire, the childs emotional difficulties improved from 1.81 ± 0.70 to 1.24 ± 0.36, social self-consciousness improved from 2.86 ± 1.03 to 1.33 ± 0.68, and physical difficulties improved from 2.14 ± 0.75 to 1.32 ± 0.39. Ninety-seven percent of patients thought that surgery improved how their chest looked. CONCLUSIONS. Surgical repair of pectus excavatum can significantly improve the body image difficulties and limitations on physical activity experienced by patients. These results should prompt physicians to consider the physiologic and psychological implications of pectus excavatum just as they would any other physical deformity known to have such consequences.


Journal of Clinical Oncology | 2000

Tandem High-Dose Therapy in Rapid Sequence for Children With High-Risk Neuroblastoma

Stephan A. Grupp; Julie W. Stern; Nancy Bunin; Cheryl Medeiros Nancarrow; Amy Ross; Mark Jeffrey Mogul; Roberta H. Adams; Holcombe E. Grier; Jed Gorlin; Robert C. Shamberger; Karen C. Marcus; Donna Neuberg; Howard J. Weinstein; Lisa Diller

PURPOSE Advances in chemotherapy and supportive care have slowly improved survival rates for patients with high-risk neuroblastoma. The focus of many of these chemotherapeutic advances has been dose intensification. In this phase II trial involving children with advanced neuroblastoma, we used a program of induction chemotherapy followed by tandem high-dose, myeloablative treatments (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence. PATIENTS AND METHODS Patients underwent induction chemotherapy during which peripheral-blood stem and progenitor cells were collected and local control measures undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart. Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of HDT/SCR were completed. RESULTS Pheresis was possible in the case of all patients, despite their young ages, with an average of 7.2 x 10(6) CD34(+) cells/kg available to support each cycle. Engraftment was rapid; median time to neutrophil engraftment was 11 days. Four patients who completed the first HDT course did not complete the second, and there were three deaths due to toxicity. With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained event-free. The 3-year event-free survival rate for these patients was 58%. CONCLUSION A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.

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Daniel M. Green

St. Jude Children's Research Hospital

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Gerald M. Haase

Boston Children's Hospital

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Craig W. Lillehei

Boston Children's Hospital

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