Biomedical subjects

Catherine A Billups

Publications and source records attributed to Catherine A Billups.

30 records · Page 2Linked to original sources

PubMed2004

Outcome after local recurrence of osteosarcoma: the St. Jude Children's Research Hospital experience (1970-2000).

BACKGROUND: Despite improvements in therapy for osteosarcoma, approximately 4-10% of patients experience a local recurrence and have a poor prognosis. METHODS: The authors analyzed prognostic factors for survival in 26 patients with a local recurrence of osteosarcoma who were treated between 1970 and 2000. RESULTS: The initial surgical procedure was amputation in 20 patients (76.9%) and limb salvage in 6 patients (23.1%). The median time from the diagnosis of osteosarcoma to local recurrence was 1.2 years (range, 1.2 months-6.1 years). Eleven patients (42.3%) developed an isolated local recurrence and 15 patients (57.7%) developed local and distant recurrence. The 5-year estimate of postrecurrence survival (PRS) (+/- 1 standard error) for the 26 patients was 19.2% +/- 7.7%. Recurrence > or = 2 years from the time of diagnosis was found to predict a better outcome (5-year PRS of 50.0% +/- 20.4%) compared with earlier recurrence (10.0% +/- 5.5%) (P = 0.037). Patients with negative margins after initial surgery were found to have improved survival (5-year PRS of 33.3% +/- 13.6%) compared with patients with positive margins (7.1% +/- 4.9%) (P = 0.015). Patients who underwent complete surgical resection at the time of recurrence were found to have a better PRS (5-year PRS of 41.7% +/- 14.2%) compared with patients who did not undergo surgery (0% +/- 0%) (P < 0.001). CONCLUSIONS: The prognosis for patients after local recurrence of osteosarcoma is poor. Complete surgical resection at the time of recurrence is essential for survival. Positive margins at the time of initial surgical resection and early recurrence appear to be poor prognostic factors.

Adolescent↗

PubMed2004

Efficacy of combined surgery and irradiation for localized Ewings sarcoma family of tumors.

BACKGROUND: Local tumor control for patients with Ewings sarcoma family of tumors (ESFT) is favorable when the primary tumor is resectable or small. Local failure rates for patients who received combined surgery and RT were reviewed to determine outcome and prognostic factors. PROCEDURES: We performed a retrospective review of all patients with localized ESFT treated with combined definitive surgery and RT between 1978 and 2001, at St. Jude Children's Research Hospital. Rates of local failure, survival, and prognostic factors for recurrence were determined in 39 patients who received combined local therapy. Systemic treatment included vincristine, actinomycin D, cyclophosphamide, and doxorubicin (6 patients), with the addition of ifosfamide and etoposide (33 patients). RESULTS: With a median follow-up of 8.7 years the 5- and 8-year survival estimates were 89.2 +/- 5.4% and 82.8 +/- 7.3%. The 8-year incidence of local failure was 10.8 +/- 5.2%. The 8-year local failure rate for patients with positive surgical margins was 17% and for negative surgical margins 5% (P = 0.25). Overall survival was improved for patients with negative surgical margins (94 vs. 71%, P = 0.052). Tumor size, site, histologic response, and radiation dose did not significantly alter the rate of local failure. CONCLUSIONS: Patients with ESFT managed with definitive surgery and irradiation have favorable local control rates. Even among patients with unfavorable prognostic factors local tumor control remained excellent.

Adolescent↗

PubMed2004

Adenocarcinoma of the cervix and vagina in pediatric patients.

Here we report our combined analysis of vaginal mesonephric adenocarcinoma (MA) in a 13 years old treated at our institution and of reported vaginal or cervical MA and clear-cell adenocarcinoma in 37 patients 18 years old or younger. Tumors in 27 patients arose in the vagina; 8 (21%) had metastases at diagnosis. The predominant symptom was vaginal bleeding; 62% of patients were exposed to diethylstilbestrol in utero. The 3-year survival estimate was 71% +/- 11%. Surgical treatment and metastasis at diagnosis were significant predictors of survival. The association between tumor excision and excellent outcome suggests that radical hysterectomy or pelvic exenteration is unnecessary. Radiotherapy as an adjunct may have contributed to this outcome.

Adenocarcinoma↗

PubMed2003

Interferon-gamma pharmacokinetics and pharmacodynamics in patients with colorectal cancer.

PURPOSE: The study objectives were to define subcutaneous (s.c.) interferon gamma (IFN-gamma) disposition in patients with gastrointestinal malignancies receiving 5-fluorouracil (5-FU) and leucovorin (LV) and to examine the relationship between IFN-gamma exposures and Fas upregulation in vivo and in vitro. METHODS: Patients received IFN-gamma (10, 25, 50, 75, and 100 microg/m(2)) with LV and 5-FU, and serial samples were collected after the first dose. IFN-gamma concentrations were measured by ELISA. A linear one-compartment model with a lag was fitted to the IFN-gamma plasma concentration-time data. To examine the relationship between IFN-gamma systemic exposure and biological activity in vivo, cell surface Fas upregulation was assessed in peripheral blood mononuclear cell (PBMC) subcompartments. RESULTS: The median (range) apparent IFN-gamma clearance was 46 l/m(2) per hour (2.6-92 l/m(2) per hour). With increasing IFN-gamma dosages, the area under the concentration-time curve (AUC(0--> infinity )) and C(max) increased; however, significant interpatient variability was observed. IFN-gamma AUC(0--> infinity ) and time above 33.3 pg/ml significantly correlated with Fas upregulation in several PBMC compartments, but dosage was significantly correlated with this pharmacodynamic marker only in CD4(+) and CD56(+) cells. In vitro studies in HT29 cells demonstrated that clinically relevant IFN-gamma concentrations (1 to 10 U/ml for 6.5 h) with 5-FU/LV upregulated Fas expression 3.5-fold, similar to that in PBMC in vivo. CONCLUSIONS: We characterized IFN-gamma disposition and developed a limited sampling model for use in future pharmacokinetic studies. Our results showed that IFN-gamma upregulates Fas in PBMC in vivo and in HT29 cells in vitro at tolerable, clinically relevant exposures and that monitoring IFN-gamma pharmacokinetics/pharmacodynamics may be warranted in IFN-gamma clinical use.

Adult↗

PubMed2003

Malignant fibrous histiocytoma and other fibrohistiocytic tumors in pediatric patients: the St. Jude Children's Research Hospital experience.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is a controversial entity. In the current study, the authors reviewed their institutional experience with these tumors to characterize their clinical features in pediatric patients and assess the impact of surgical resection on outcome. METHODS: The records of the 28 patients who were diagnosed with MFH or MFH variants of soft tissue between January 1971 and December 2000 were reviewed and the tumors were reclassified according to the World Health Organization guidelines. RESULTS: Seventeen patients had MFH; 10 patients had angiomatoid fibrous histiocytoma (FH), and 1 patient had a plexiform fibrohistiocytic tumor. The median age of patients at the time of diagnosis was 7.3 years. The most common primary tumor site was the extremity (n = 14). Metastatic disease (to the lung) was present in only three patients, each of whom had MFH. Of the 17 MFH tumors, 13 were high grade, 8 were invasive, and 6 measured > 5 cm. All angiomatoid FH tumors and the plexiform fibrohistiocytic tumor were noninvasive, and 10 measured < or = 5 cm. Surgical treatment was comprised of wide local excision with clear margins (n = 18), amputation (n = 3), excision with positive or indeterminate surgical margins (n = 4), partial resection (n = 2), or biopsy only (n = 1). Primary reexcision was performed for 21 patients. The 5-year survival and event-free survival (EFS) estimates for patients with MFH were 76.5% +/- 11.2% and 70.6% +/- 12.1%, respectively; the 5-year survival and EFS estimates were 100% +/- 0% for patients with angiomatoid FH or plexiform fibrohistiocytic tumor. Compared with partial resection or excision, wide local excision or amputation was found to have a positive impact on the probability of EFS in patients with localized disease (P = 0.008). All four patients with metastatic or unresectable MFH had died by the time of last follow-up. CONCLUSIONS: MFH should be distinguished from angiomatoid FH and plexiform fibrohistiocytic tumors, both of which are less aggressive. Wide local excision is the treatment of choice, regardless of the histology or grade of the tumor. Patients with metastatic or unresectable MFH appear to have a poor outcome and would benefit from more effective therapies.

Adolescent↗

PubMed2003

Treatment of intraocular retinoblastoma with vincristine and carboplatin.

PURPOSE: To evaluate the efficacy of chemoreduction using vincristine and carboplatin in preventing or delaying external-beam radiotherapy (EBRT) or enucleation in patients with intraocular retinoblastoma. PATIENTS AND METHODS: Twenty-five patients (43 eyes) with newly diagnosed intraocular retinoblastoma received primary treatment with eight courses of vincristine and carboplatin. Focal treatments were delayed until documentation of disease progression. Outcome measures for each eye were length of time to disease progression, avoidance or delay of EBRT, and globe survival. Event-free survival was defined as the length of time to EBRT or enucleation. RESULTS: Disease in all eyes responded to chemotherapy and progressed in only two patients before completion of the eight courses of therapy. Disease in all but four eyes progressed and required focal treatments. Event-free survival estimates at 2 years were 59.2% +/- 12.0% for Reese-Ellsworth group I, II, and III eyes and 26.3% +/- 9.2% for group IV and V eyes. Nineteen eyes (44.2%) required EBRT and 13 eyes (30.2%) were enucleated. The ocular salvage rate was 83.3% for Reese-Ellsworth group I to III eyes and 52.6% for group IV and V eyes. For those patients receiving EBRT, the median time from enrollment to EBRT was 9.5 months (median age at EBRT, 21 months). CONCLUSION: In combination with appropriate early intensive focal treatments, chemoreduction with vincristine and carboplatin, without etoposide, may be an alternative treatment for patients with early-stage intraocular retinoblastoma, although additional studies are needed. Patients with advanced intraocular disease require more aggressive treatments.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Clinical and biologic significance of nuclear unrest in Wilms tumor.

BACKGROUND: Nuclear unrest is a term applied to Wilms tumors (WT) with favorable histology that show nuclear enlargement similar to that seen in anaplasia but with no abnormal mitotic figures. This study was undertaken to evaluate the clinical and pathogenetic significance of WT with nuclear unrest. METHODS: The authors reviewed primary nephrectomy specimens and clinical data from 173 patients who were treated for WT on 1 of 5 consecutive clinical trials at St. Jude Children's Research Hospital. A subset of 70 patients was selected for p53 immunohistochemistry. Seventeen samples of recurrent tumors were also reviewed. RESULTS: WT with nuclear unrest had age and stage distribution similar to that for WT with favorable histology. Patients who had tumors with favorable histology, nuclear unrest, and anaplastic histology had 5-year cumulative incidences of recurrence of 12.2%, 22.2%, and 36.4%, respectively (P = 0.010). Despite the difference in recurrence incidence, patients who had tumors with nuclear unrest and patients who had tumors with favorable histology had nearly identical overall survival. Immunostaining for p53 was positive in 2 of 24 tumors (8.3%) with favorable histology, 1 of 25 tumors (4%) with nuclear unrest, and 16 of 21 tumors (76%) with anaplastic histology (P < 0.001). Histologic review of samples from recurrent tumors showed that 7 of 10 of primary tumors converted from favorable histology to either nuclear unrest or anaplastic histology in the recurrent tumor. CONCLUSIONS: WT with nuclear unrest more closely resembles favorable histology than anaplastic histology, both clinically and pathogenetically. Analysis of samples from recurrent tumors suggests that WT with nuclear unrest represents an intermediary in the continuum from favorable histology to anaplastic histology. For treatment stratification, it is appropriate to continue grouping nuclear unrest with favorable histology, although a larger analysis will be necessary to confirm the current findings.

Adolescent↗

PubMed2003

Benefit of surgical resection of invasive pulmonary aspergillosis in pediatric patients undergoing treatment for malignancies and immunodeficiency syndromes.

PURPOSE: The aim of this study was to evaluate the outcome of children undergoing treatment for malignancy and immunodeficiency syndromes in whom invasive pulmonary aspergillosis (IPA) developed. METHODS: The authors reviewed the medical records of all patients treated at their institution from January 1990 to August 1999 for culture-proven pulmonary aspergillus infection. RESULTS: Among the 43 patients studied, the median age at the time of diagnosis of IPA was 13.1 years. The most common primary diagnoses were acute myelogenous leukemia (n = 18) and acute lymphoblastic leukemia (n = 14); 27 patients (63%) had received a bone marrow transplant (BMT). Of the 18 patients who underwent surgical intervention for IPA, 14 (78%) had one operation, whereas the remaining 4 patients had 2. The 4 patients alive at the time this report was written had undergone surgical intervention 2, 10, 23, and 44 months previously respectively. Surgical resection of the involved lung parenchyma was significantly prognostic for survival (P <.001). Other factors that influenced outcome were the extent of pulmonary invasion, steroid use, and the timing of bone marrow transplantation (BMT) in regard to the diagnosis of IPA. CONCLUSIONS: The overall mortality rate of children treated for malignancies and immunodeficiency syndromes in who IPA develops remains high, and antifungal therapy alone may not be curative. Surgical resection may provide a small but possibly the only chance for survival. Therefore, we would advocate for resection of all involved tissue, even if it requires reoperation.

Adolescent↗

PubMed2002

Real-time polymerase chain reaction as an aid for the detection of SYT-SSX1 and SYT-SSX2 transcripts in fresh and archival pediatric synovial sarcoma specimens: report of 25 cases from St. Jude Children's Research Hospital.

Synovial sarcoma is the most common nonrhabdomyosarcomatous soft tissue sarcoma in children and adolescents and is characterized by a reciprocal t(X;18)(p11;q11) which results in the fusion of the SYT gene on chromosome 18q11 to either of two closely related genes, SSX1 (Xp11.23) or SSX2 (Xp11.21). Detection of this translocation or its resultant gene fusion by molecular methods is helpful in the pathologic diagnosis of synovial sarcoma, especially in poorly differentiated tumors. This study was designed to evaluate the utility of a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect and distinguish SYT-SSX1 and SYT-SSX2 fusions in fresh and archival specimens of synovial sarcoma in pediatric patients seen at St. Jude Children's Research Hospital. In addition, the clinicopathologic features of the tumors with SYT-SSX1 vs. SYT-SSX2 fusions were compared. The 25 patients studied had a median age of 13 years 9 months (range 5 to 19 years). Estimates of survival and event-free survival at 5 years were 78.7 +/- 10.5% and 56.2 +/- 13.2%, respectively. Seventeen (68%) tumors were monophasic, eight (32%) were biphasic. Seven tumors contained poorly differentiated areas. Positive results for either SYT-SSX1 or SYT-SSX2 were obtained in 21/25 (84%) cases. Three cases did not have a detectable gene fusion and one had no amplifiable RNA. SYT-SSX1 transcripts were found in 18/24 (75%) of the tumors while SYT-SSX2 transcripts were identified in 3/24 (12.5%). All of the poorly differentiated tumors and seven out of eight tumors from patients who developed lung metastases had an SYT-SSX1 fusion transcript. Real-time PCR is useful in detecting and distinguishing SYT-SSX1 from SYT-SSX2 gene fusions in synovial sarcoma. Valuable aspects of this methodology are the applicability to both frozen and formalin-fixed samples, decreased labor costs, and the rapidity of results. In addition, distinguishing SYT-SSX1 from SYT-SSX2 fusions with these methods allow for prospective collection of information that may clarify issues of prognostic relevance.

Adolescent↗

PubMed2002

Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma.

PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). PATIENTS AND METHODS: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival. RESULTS: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% +/- 9% and 56% +/- 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% +/- 10%). CONCLUSION: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.

Adolescent↗

PubMed2002

Survival after recurrence of Ewing tumors: the St Jude Children's Research Hospital experience, 1979-1999.

BACKGROUND: Despite improved therapies, 30-40% of patients with Ewing tumors (ET) experience recurrence and have a poor prognosis. The authors analyzed factors prognostic of survival in patients with recurrent ET. METHODS: The authors assessed the relation between postrecurrence survival (PRS) and demographic, disease, and treatment factors in 71 patients who experienced recurrent ET after treatment on one of three consecutive institutional protocols. RESULTS: Thirty-four patients (47.9%) had distant recurrence, 25 patients (35.2%) had local recurrence, and 12 patients (16.9%) had both distant and local recurrence at a median of 1.7 years after diagnosis. The probability of 5-year PRS (+/- 1 standard error) was 17.7%+/-4.5%. Recurrence > or = 2 years after diagnosis predicted a significantly better outcome (5-year PRS, 34.9%+/-8.5%) compared with earlier recurrence (5.0%+/-2.8%; P < 0.001). Patients who had both local and distant recurrence fared worse (5-year PRS, 12.5%+/-8.3%) compared with patients who had local recurrence alone (21.7%+/-7.8%) or distant recurrence alone (17.6+/-6.1%). Among patients with local recurrence alone, those who underwent salvage with radical surgery had significantly higher 5-year PRS estimates (31.4%+/-11.6%) compared with the other patients (9.1%+/-6.1%; P = 0.023). Pulmonary irradiation significantly improved the outcomes of patients with isolated pulmonary recurrence (5-year PRS estimate, 30.3%+/-12.5% vs. 16.7%+/-10.8%, respectively; P = 0.018). CONCLUSIONS: Although outcomes are generally poor after patients experience recurrence of ET, certain patient groups differ appreciably in their likelihood of survival. Patients who experience recurrence > or = 2 years after diagnosis and patients who have local recurrence that can be treated with radical surgery and intensive chemotherapy have the most favorable outcomes.

Adolescent↗

PubMedDate not supplied

Improved survival for patients with recurrent Wilms tumor: the experience at St. Jude Children's Research Hospital.

BACKGROUND: Reported estimates of survival for patients with recurrent Wilms tumor are 24% to 43%. Because published survival data are more than a decade old and do not reflect advances in therapy, the authors reviewed their experience in treating recurrent Wilms tumor to determine whether the probability of survival has increased. PATIENTS AND METHODS: The authors reviewed the cases of 54 patients with recurrent Wilms tumor who were treated on one of six consecutive clinical trials at St. Jude Children's Research Hospital between 1969 and 2000. RESULTS: Five-year overall survival estimates after relapse were 63.6 +/- 15.7% for patients treated during or after 1984 (n = 20) and 20.6 +/- 6.5% for patients treated before 1984 (n = 34) (P = 0.002). When the analysis was restricted to patients with high-risk clinical features, 5-year overall survival estimates were 47.6 +/- 15.7% for those treated in the modern era (n = 16) and 11.1 +/- 5.2% for those treated in the earlier era (n = 25) (P = 0.005). Only three patients received high-dose chemotherapy with autologous stem cell rescue; one survived. No patients with recurrent anaplastic histology disease survived. CONCLUSIONS: Significant progress has been achieved in the treatment of recurrent favorable-histology Wilms tumor using multimodality salvage regimens with conventional doses of chemotherapy. Novel therapeutic strategies will be necessary to cure patients with recurrent anaplastic Wilms tumor.

Adolescent↗