Endoscopic retrograde cholangiopancreatography after pancreaticoduodenectomy for benign and malignant disease: indications and technical outcomes.

BACKGROUND AND STUDY AIMS: Patients undergoing pancreaticoduodenectomy develop postoperative complications related to surgery and their disease. Very little data are available on the role or success of endoscopic retrograde cholangiopancreatography (ERCP) in such patients. The aim of this study was to evaluate the indications and role of diagnostic and therapeutic ERCP after pancreaticoduodenectomy for both benign and malignant disease. PATIENTS AND METHODS: This study was a 10-year (1990 - 2000) single institution retrospective review of all ERCPs performed on patients who had undergone pancreaticoduodenectomy surgery. Indications for the ERCP and technical procedural success were studied. RESULTS: 29 patients with a pancreaticoduodenectomy underwent 56 ERCPs. Reasons for surgery were neoplasia and chronic pancreatitis. Indications for ERCP included evaluation of jaundice and pain. Technical success related to the clinical indication (jaundice 69 %, pain 54 %). CONCLUSION: ERCP plays an important role in the management of postpancreatic surgery problems including biliary and anastomotic strictures, and should be the modality of choice. However, surgical technique may make the afferent limb inaccessible, and the ductal anastomosis difficult to identify in patients with some types of pancreaticoduodenectomy. Closer collaboration between surgeon and endoscopist may allow alterations in surgical technique to improve postoperative ERCP success.

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Efficacy of ifosfamide and doxorubicin given as a phase II "window" in children with newly diagnosed metastatic rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: The cure rate for children/adolescents with localized rhabdomyosarcoma (RMS) has tripled over the past 25 years, but patients with metastatic disease at presentation have not benefited similarly, and urgently need new therapy. We evaluated a new drug pair, ifosfamide + doxorubicin, for such patients. PROCEDURE: We estimated the complete and partial response rates (i.e., CR and PR) of 152 previously untreated children/adolescents with metastatic RMS entered on the IRS-IV pilot from July 1988 to October 1991 who received an "up-front window" of ifosfamide (1.8 gm/m(2)/day for 5 days) and doxorubicin (30 mg/m(2)/day for 2 days) given every 3 weeks for 12 weeks. This was followed by combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide (VAC), given every 3 weeks for an additional 36 weeks. RESULTS: Of 115 patients evaluable for early response at 12 weeks, 28 (20%) had CR and 66 (43%) had PR. The ultimate CR rate was 52%. Overall, about one-third of patients survived. Prognostic factor analysis revealed that patients < 10 years old (P < 0.001), those with embryonal tumors (P = 0.002), or a GU primary site (P = 0.010), and those who lacked nodal disease (P = 0.041), and those who lacked bone or bone marrow metastasis (P < 0.001) fared better than did others. CONCLUSIONS: The 63% CR + PR rate achieved at 12 weeks and overall 5-year FFS seen with this drug pair is similar to that achieved with previously evaluated drug combinations. We conclude that ifosfamide/doxorubicin is highly active in advanced RMS, and should be considered for inclusion in frontline therapy for children with intermediate or high-risk RMS.

Intraoperative high-dose-rate brachytherapy for the treatment of pediatric tumors: the Ohio State University experience.

PURPOSE: To determine whether intraoperative high-dose-rate brachytherapy (IO-HDRBT) can be used to decrease the dose of external beam radiotherapy (EBRT) in the treatment of children with soft-tissue sarcomas and, thereby, reduce morbidity without compromising local control. METHODS AND MATERIALS: From March 1992 through April 1999, 13 pediatric patients were treated with IO-HDRBT, low-dose EBRT, chemotherapy, and radical surgery at 21 sites that were not amenable to intraoperative electron beam therapy. The IO-HDRBT dose at 5 mm depth was 10 to 12.5 Gy for close margins/microscopic disease at 14 sites and 12.5 to 15 Gy for gross disease at 7 sites. The treatment volumes ranged from 4 to 96 cm(3) (mean 27). The EBRT dose was limited to 27-30 Gy in most cases to minimize growth retardation and preserve normal organ function. RESULTS: After a median follow-up of 47 months (range 12-97), 11 patients were alive and without evidence of disease (overall survival rate 85%, 4-year actuarial survival rate 77%). Of the 2 who died, 1 had Stage III pulmonary blastoma with a sacral recurrence; the other had Stage IV undifferentiated synovial sarcoma with a pulmonary recurrence. One local failure occurred in a patient with gross residual disease after incomplete resection for Stage IV pulmonary blastoma. The local control rate was 95%, and morbidity was observed in 3 patients (23%). One patient developed impaired orbital growth with mild ptosis. Another patient required orthopedic pinning of her femoral subcapital epiphysis and construction of a neobladder secondary to urethral obstruction. The third patient required reimplantation of her autotransplanted kidney secondary to chronic urinary tract infection and ureteral reflux. CONCLUSIONS: IO-HDRBT allowed for reduction in EBRT without compromising local control or disease-free survival in children with soft-tissue sarcomas. Tumor beds inaccessible to electron beam methods could be satisfactorily encompassed with IO-HDRBT techniques.

Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease.

PURPOSE: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy. PATIENTS AND METHODS: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT). RESULTS: Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P =.42). No significant difference in outcome was noted with HF-RT versus C-RT (P =.85 and P =.90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%. CONCLUSION: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.

Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction.

BACKGROUND: The endoscopically placed enteral stent has emerged as a reasonable alternative to palliative surgery for malignant intestinal obstruction. This is a report of our experience with the use of enteral stents for nonesophageal malignant upper GI obstruction. METHODS: Data on all patients who had undergone enteral stent placement were reviewed. Those with a diagnosis of pancreatic cancer were compared with another similar cohort of patients who underwent palliative gastrojejunostomy. RESULTS: Thirty-one procedures were performed on 29 patients (mean age 67.7 years). Thirteen (45%) were men and 16 (55%) women. The diagnoses were gastric (13.8%), duodenal (10.3%), pancreatic (41.4%), metastatic (27.6%), and other malignancies (6.9%). Malignant obstruction occurred at the pylorus (20.7%), first part of duodenum (37.9%), second part of duodenum (27.6%), third part of duodenum (3.5%), and anastomotic sites (10.3%). Twenty-nine (93.5%) procedures were successful and good clinical outcome was achieved in 25 (80.6%). Re-obstruction by tumor ingrowth occurred in 2 patients after a mean of 183 days. The median survival time for patients with pancreatic cancer who underwent enteral stent placement compared with those who underwent surgical gastrojejunostomy was 94 and 92 days, charges were $9921 and $28,173, and duration of hospitalization was 4 and 14 days, respectively (latter 2 differences with p value < 0.005). CONCLUSION: Endoscopic enteral stent placement of nonesophageal malignant upper GI obstruction is a safe, efficacious, and cost-effective procedure with good clinical outcome, lower charges, and shorter hospitalization period than the surgical alternative.

Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.

PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

Variables influencing end-of-life care in children and adolescents with cancer.

BACKGROUND: The purpose of this study was to describe the variables influencing end-of-life care in children and adolescents dying of cancer. MATERIALS AND METHODS: Records of 146 children with cancer who died at Children's Hospital were reviewed for demographics, diagnosis, location of death, withdrawal of life support, use of "do not resuscitate" (DNR) orders, and the length of time that those orders were in effect. RESULTS: Ninety-five patients were evaluated. Fifty-nine died of progressive disease and 36 deaths were therapy-related. Sixty-four percent of disease-related deaths occurred at home with support from home care or hospice. Only 10% of all patients died while receiving maximal aggressive support in the intensive care unit. Age, diagnosis (solid tumor vs. leukemia), cause of death, length of last hospital admission, and the duration of DNR orders had a significant correlation with the place of death and referral to and use of hospice. Thirty-five percent of all patients had hospice support. CONCLUSIONS: Most children who die of cancer die because of progressive disease at home with hospice support. Do not resuscitate orders were written for most patients who died. End-of-life decisions are influenced by patient diagnosis, cause of death, and age.

TEL/AML-1 fusion gene. its frequency and prognostic significance in childhood acute lymphoblastic leukemia.

TEL gene rearrangement due to the 12;21 chromosome translocation is believed to be the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL). A study was conducted to investigate the frequency and prognostic significance of TEL/AML-1 fusion gene resulting from a cryptic t(12;21)(p13;q22). Bone marrow samples from 86 patients diagnosed over the past 5 years at Columbus Children's Hospital were analyzed by fluorescence in situ hybridization (FISH) technique for TEL/AML-1 fusion gene, using LSI((R)) DNA probes. The positive cases were analyzed for clinical outcome. Patients in this study received treatment according to Children's Cancer Group (CCG) protocols. Fifteen of the 86 cases (17%) were positive for the fusion gene. All were B-cell lineage and except for one, all were CD10 positive. TEL/AML-1 was not found in any T-cell ALL. The mean overall survival (OS) following diagnosis for the TEL/AML-1-positive group was significantly longer than for the TEL/AML-1-negative group by log-rank = 7.84, P = 0.005. Similarly, the event-free survival (EFS) after remission for the positive group (median 94.5 months) was longer than the negative group (median 57 months) by log-rank = 7.19, P = 0.007. This study confirms that the TEL/AML-1 fusion gene may be the most common genetic event in childhood ALL, occurring in 17% of the patients. It appears restricted to the B-cell lineage. In this study, the presence of a TEL/AML-1 fusion gene was statistically significant in predicting both OS and EFS, indicating a favorable clinical outcome for these patients. Screening for TEL/AML-1 should become routine at diagnosis and a useful biological variable for risk stratification in future clinical trials.

Progress in the diagnosis and treatment of rhabdomyosarcoma and related soft tissue sarcomas.

Advances in the diagnosis and treatment of rhabdomyosarcoma and related soft tissue sarcomas continue in the Intergroup Rhabdomyosarcoma Study Group (IRSG) and European cooperative groups. The use of molecular biology techniques in soft tissue sarcomas are redefining the classic pathology of these small blue cell tumors. Improvements in imaging, radiotherapy, and surgery, in part, deserve credit for the better survival seen in all cooperative trials. These advances confound the interpretation of consecutively run chemotherapy trials using historical comparisons. The IRSG has reported improvement in the prognosis of both nonmetastatic and metastatic embryonal rhabdomyosarcoma as attributable to three, three-drug regimens that use cyclophosphamide at 2.2 g/m2 in either maintenance or induction and maintenance therapy. Patients of any age with metastatic, nonembryonal, and those over 10 years of age with metastatic embryonal rhabdomyosarcoma continue to have a poor prognosis, which even megatherapy has failed to change. The doublet of ifosfamide and etoposide in combination with vincristine, actinomycin D, and cyclophosphamide at 2.2 g/m2 achieved a remarkable 3-year survival of 58% in patients with metastatic rhabdomyosarcoma and undifferentiated soft tissue sarcoma. The topoisomerase I inhibitor, topotecan, has recently been found by the IRSG to have a 57% overall response rate in patients with metastatic alveolar rhabdomyosarcoma. Topotecan has completed testing with cyclophosphamide in a phase II window study in newly diagnosed patients with metastatic disease and has been incorporated into a randomized trial in intermediate risk patients in IRSG-V. Molecular studies in IRSG-V will be applied in the detection of occult bone marrow metastases and the evaluation of resection margins at initial and second-look surgery. Long-term follow-up will be required in patients with gross residual sarcoma randomized to conventional and hyperfractionated radiotherapy in IRSG-IV to assess late effects. Although older patients with unfavorable histology and metastatic disease continue to have a poor prognosis, the overall 5-year survival of children and adolescents with nonmetastatic and metastatic rhabdomyosarcoma is approaching 80%. As molecular discoveries advance the diagnosis and detection of rhabdomyosarcoma, it is hoped that the futuristic molecular based treatment strategies in development and early testing will further improve survival in high-risk patients with metastatic soft tissue sarcoma.

Neurofibromatosis-Noonan syndrome and acute lymphoblastic leukemia: a report of two cases.

Two boys with neurofibromatosis-Noonan syndrome in whom acute lymphoblastic leukemia (ALL) developed are described. Both patients demonstrated B-lineage leukemias with normal cytogenetics. They were treated with combination chemotherapy and remain in remission off therapy. Patients with neurofibromatosis-Noonan syndrome may be at increased risk for ALL.

Use of brachytherapy to preserve function in children with soft-tissue sarcomas.

Pediatric soft-tissue sarcomas are managed with a multimodality treatment program that includes surgery, chemotherapy, and external-beam radiotherapy (teletherapy). The use of teletherapy in young children can result in significant long-term toxicities (especially growth retardation of bones and organs). Brachytherapy, if feasible, is an attractive alternative for the treatment of pediatric soft-tissue sarcomas, since it irradiates small volumes and, thus, may potentially minimize complications. Aggressive chemotherapy is used to achieve systemic control and tumor shrinkage, thereby facilitating conservative surgery and brachytherapy. The brachytherapy techniques used in children are similar to those employed in adults. Low-dose-rate (LDR) brachytherapy with manually afterloaded removable iridium-192 is commonly used, although it is associated with some radiation exposure hazards. Low-energy radionuclides (e.g., iodine-125) and remote afterloading technology have been used to reduce radiation exposure hazards. Brachytherapy, in conjunction with chemotherapy and surgery but without supplementary teletherapy, has produced good local control with acceptable late complications in selected patients with localized tumors. Brachytherapy can also be used as a boost to moderate dose external-beam radiotherapy for more extensive tumors. The use of newer modalities, such as high-dose-rate, pulsed-dose-rate, and intraoperative brachytherapy, has allowed brachytherapy to be given to younger children and infants, but the long-term morbidities of these modalities need to be established.

Accuracy and complication rate of brush cytology from bile duct versus pancreatic duct.

BACKGROUND: The accuracy and complication rates of brush cytology obtained from pancreaticobiliary strictures have not been fully defined. In this study we compared the accuracy and complications of brush cytology obtained from bile versus pancreatic ducts. METHODS: We identified 148 consecutive patients for whom brush cytology was done during an ERCP from a database with prospectively collected data. We compared cytology results with the final diagnosis as determined by surgical pathologic examination or long-term clinical follow-up. We followed all patients and recorded ERCP-related complications. RESULTS: Forty-two pancreatic brush cytology samples and 101 biliary brush cytology samples were obtained. The accuracy rate of biliary cytology was 65 of 101 (64.3%) and the accuracy rate of pancreatic cytology was 30 of 42 (71.4%). Overall sensitivity was 50% for biliary cytology and 58.3% for pancreatic cytology. Of 67 patients with pancreatic adenocarcinoma, sensitivity for biliary cytology was 50% versus 66% for pancreatic cytology. Concurrent pancreatic and biliary cytology during the same procedure increased the sensitivity in only 1 of 10 (10%) patients. Pancreatitis occurred in 11 (11%) patients (9 mild cases, 2 moderate cases) after biliary cytology and in 9 (21%) patients (6 mild cases, 3 moderate cases) after pancreatic cytology (p = 0.22). In 10 patients who had pancreatic brush cytology, a pancreatic stent was placed. None of these patients developed pancreatitis versus 9 of 32 (28%) patients in whom a stent was not placed (p = 0.08). Pancreatic cytology samples obtained from the head of the pancreas were correct in 13 of 18 (72%) cases, from the genu in 7 of 7 (100%) cases, from the body in 5 of 9 (55%) cases, and from the tail in 4 of 7 (57%) cases. CONCLUSION: The accuracy of biliary brush cytology is similar to the accuracy of pancreatic brush cytology. The yield of the latter for pancreatic adenocarcinoma is similar to that of the former. Complication rates for pancreatic cytology are not significantly higher than the rates for biliary cytology. The placement of a pancreatic stent after pancreatic brushing appears to reduce the risk of postprocedure pancreatitis.

Management of occluded biliary Wallstents.

BACKGROUND: Wallstents (Schneider Stent, Inc., USA) used for the palliation of malignant biliary strictures, although associated with prolonged patency, can occlude. There is no consensus regarding the optimal management of Wallstent occlusion. AIMS: To evaluate the efficacy of different endoscopic methods for managing biliary Wallstent occlusion. METHODS: A multicentre retrospective study of patients managed for a biliary Wallstent occlusion. RESULTS: Data were available for 38 patients with 44 Wallstent occlusions, all of which had initial endoscopic management. Twenty four patients had died and 14 were alive after a median follow up of 231 (30-1095) days following Wallstent occlusion. Occlusions were managed by insertion of another Wallstent in 19, insertion of a plastic stent in 20, and mechanical cleaning in five. Endoscopic management was successful in 43 (98%). Following management of the occlusion, bilirubin decreased from 6.0 (0.5-34.3) to 2.1 (0.2-27.7) mg/100 ml (p < 0.05). No complications occurred. The median duration of second stent patency was 75 days (95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days (71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after mechanical cleaning (NS). The respective median survivals were 70 days (22-118), 98 days (54-142), and 34 days (30-380) (NS). Incremental cost effective analysis showed that plastic stent insertion is the most cost effective option. CONCLUSION: Although all three methods are equally effective in managing an occluded Wallstent, the most cost effective method appears to be plastic stent insertion.

Feasibility of intraoperative high-dose rate brachytherapy to boost low dose external beam radiation therapy to treat pediatric soft tissue sarcomas.

PURPOSE: To determine if a single intraoperative high-dose-rate brachytherapy (IOHDR) dose can be used in conjunction with low dose external beam radiation therapy (EBRT) to treat soft tissue malignancies in children with reduced morbidity. METHODS: From March 1992 to February 1995, six pediatric patients (4 boys, 2 girls; ages ranging from 4-13 years; median 10.5 years) were treated with IOHDR in conjunction with EBRT, chemotherapy, and radical surgery at nine sites not treatable by standard intraoperative electron beam radiation therapy techniques. The IOHDR dose was 10 Gy (at 7 sites with microscopic residual disease) or 12.5 Gy (at 2 sites with minimal gross residual disease) prescribed at 0.5 cm depth. The treatment volume varied from 9-96 cc (mean 30.3 cc). IOHDR was used in these patients because the tumor locations prevented positioning and insertion of conventional intraoperative electron beam applicators. The EBRT dose was limited to 27-30.6 Gy (median dose 27.4 Gy) postoperatively in all patients to minimize growth retardation or altered organ function. The median initial EBRT field size was 211 cm2 (range 25-483), with a median of two fields per patient (range 1-2). RESULTS: After a median follow-up of 40 months (range 22-62 months), all the patients were alive, five of them without evidence of disease. The other patient, with stage IV undifferentiated synovial sarcoma developed regrowth of pulmonary metastases at 14 months and local failure at 34 months. Toxicity was seen in two patients. One patient developed recurrent urinary infections and ureteral stenosis after 6 months and required a left nephrectomy. Another developed mild to moderate loss of visual acuity and impaired orbital growth after 6 months. CONCLUSIONS: Use of IOHDR in conjunction with low dose EBRT to obtain local control and long-term disease-free survival in pediatric soft tissue sarcomas is feasible with acceptable toxicity. Tumor beds not treatable with standard electron beam intraoperative radiation therapy could be satisfactorily encompassed with IOHDR.

Mobilization of peripheral blood stem cells in children using G-CSF after carboplatin containing myelosuppressive chemotherapy.

PURPOSE: Peripheral blood stem cell (PBSC) apheresis provides an alternative to autologous marrow harvest as a source of hematologic stem cells for transplantation in children with solid tumors. PATIENTS AND METHODS: Eight children with metastatic or recurrent solid tumors underwent 27 apheresis procedures. Recovery from myelosuppressive chemotherapy occurred without continuous daily growth factor support prior to mobilization. Granulocyte colony stimulating factor (G-CSF) at 16 microgs/kg/day was used to increase stem cells in the peripheral circulation. CD 34 positive cells, mononuclear cells (MNC), and CFU-GM were measured in the apheresis products. Prior chemotherapy was examined as a clinical factor that affected PBSC yield. RESULTS: A significant correlation was found between CD 34+/kg and CFU-GM/kg of the products (r = 0.758, P < 0.001). Patients receiving cumulative doses of carboplatin over 1,600 mg/m2 produced adequate MNC (1 x 10(8)/kg) but yielded significantly less CD 34+ cells or CFU-GM than those patients receiving less carboplatin. Prior doses of etoposide and ifosfamide did not effect PBSC yield. CONCLUSIONS: The mobilization technique was well tolerated, and the products obtained produced trilineage engraftment in the patients that underwent peripheral blood stem cell transplantation. Peripheral blood stem cell apheresis in children can be optimized by selection of appropriate candidates and mobilization with G-CSF after an absence of hematopoietic growth factor support.

The National Cancer Data Base report on patterns of childhood cancers in the United States.

BACKGROUND: Patterns of and progress against childhood cancer have been reported on multi-institution, regional, national, and international bases by several sources in the past. These sources have included clinical cooperative group trials and population-based registries. In general, the population-based surveys have excluded brain tumors of either benign or uncertain behavior. The authors of this article investigated the patterns of data reported for the period 1985-1993, motivated by their interest in assessing the potential of National Cancer Data Base (NCDB) data to 1) facilitate individual institution review and 2) cover institutions that are not members of the Pediatric Oncology Group or the Children's Cancer Group, which are both national clinical cooperative groups. METHODS: Six annual calls for data, starting with a call for 1985 and 1988 cases, were issued to approximately 2100 hospitals with cancer programs (1340 programs approved by the Commission on Cancer of the American College of Surgeons and 760 other programs). The baseline data items of the NCDB included patient demography, tumor characteristics, initial treatment, and follow-up. The data for each patient were coded in the traditional manner by trained cancer registrars before being transmitted to the NCDB in standard format. RESULTS: In the most recent year for which data were reported, the NCDB included 42% of all estimated U.S. childhood cancers. The cases were reported by institutions that were members of the Pediatric Oncology Group and the Children's Cancer Group as well as nonmember institutions. The distribution of diagnostic groups reported to the NCDB was generally similar to that reported to SEER, except for lymphomas and brain cancer (the NCDB series included benign as well as malignant brain tumors). The distribution of diagnostic groups reported to the NCDB did not change over the 9-year reporting period (1985-1993). With regard to ethnicity, the most varied distribution of diagnostic groups was found among African American patients. For many types of cancer, the survival of those patients reported to the NCDB was similar to that of patients included in the SEER population-based series. These cancers included Wilms' tumor (NCDB 89% vs. SEER 88%), non-Hodgkin's lymphoma (NCDB 74% vs. SEER 70%), soft tissue sarcomas (NCDB rhabdomyosarcomas 70% and sarcomas 79% vs. SEER soft tissue sarcomas 71%), and neuroblastoma (NCDB 58% vs. SEER 57%). CONCLUSIONS: The authors concluded that the number of brain tumors of benign and uncertain behavior being diagnosed were significant enough in number that they should be included in regional and national cancer registries that report data for clinical purposes. They further concluded that for reasons of data inclusion and institutional coverage, the NCDB will be an important data base for pediatric cancers that will warrant increased use by pediatric investigators.

Innovation in the management of soft tissue sarcomas in infants and young children: high-dose-rate brachytherapy.

PURPOSE: Conventional low-dose-rate (LDR) brachytherapy is effective in treating childhood sarcomas, but often not practical (due to the associated radiation hazards) in the young children who require continuous observation and sedation. Fractionated high-dose-rate brachytherapy (HDR) was used to deliver adequate tumoricidal radiation while preserving bone and organ growth in children. MATERIALS AND METHODS: Twelve children with diverse sarcomas were treated with fractionated HDR. The median age at diagnosis was 18 months (range, 1 to 42). Nine patients had rhabdomyosarcoma and three had other soft tissue sarcoma (STS) variants. Ten patients had microscopic residual disease at the time of brachytherapy. All patients were treated with appropriate chemotherapy and surgery. HDR was delivered in 3-Gy fractions twice a day to a total dose of 36 Gy in 8 days. External-beam radiation therapy (EBRT) was avoided. Patients were monitored for a median of 61 months (range, 30 to 78). RESULTS: One patient developed local recurrence and distant metastases to the lungs. The 6-year actuarial local control and overall survival rates were 91% and 81%, respectively. Brachytherapy-related morbidity occurred in 50% of patients. The morbidity was mild to moderate in 42% of patients and consisted primarily of acute skin and mucosal reaction. One patient experienced severe (grade III to IV) toxicity. Another child, treated to the tongue, had delayed dentition only in the teeth adjacent to the brachytherapy site. The other children have exhibited only minimal or none of the bone growth retardation expected with EBRT. CONCLUSION: The combination of conservative surgery, chemotherapy, and exclusive HDR to postchemotherapy tumor volume with a modest margin, avoiding EBRT, provided disease control in carefully selected young children, while preserving bone growth and organ function. The short duration of therapy and small volume irradiated allowed chemotherapy to be resumed shortly after brachytherapy. The use of HDR challenges the present philosophy of radiotherapy treatment volume, which holds that the prechemotherapy tumor volume should be treated with an acceptable margin. Brachytherapy should be included in multicentric clinical trials in young children.