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Biomedical subjects

C B Pratt

Publications and source records attributed to C B Pratt.

At least 55 records · Page 3Linked to original sources

Comparison of primary osteosarcoma of flat bones with secondary osteosarcoma of any site.

BACKGROUND: The authors hypothesized that the outcomes for young patients who present with primary osteosarcoma of flat bones or secondary osteosarcoma after other primary malignancies are similar because the sites of these tumors rarely makes them amenable to complete surgical resection. METHODS: The authors reviewed their experience with 27 patients with primary osteosarcomas involving flat bones and 18 patients with secondary osteosarcomas of any site, evaluating treatment, metastatic patterns, and outcome. RESULTS: Eleven of the 27 primary osteosarcomas and 10 of the 18 secondary osteosarcomas were at least partially resectable at the time of initial diagnosis. At last follow-up, 10 of the 27 patients with primary flat bone osteosarcoma were alive, eight of whom were disease free. Three of 18 with the secondary osteosarcoma patients were alive, including one with locally recurrent disease after recent disease resections. Chemotherapy with single or combinations of agents rarely yielded responses for primary flat bone or secondary osteosarcomas. CONCLUSIONS: Outcome for both groups of patients was poor due to metastases and failure of local control. Sixteen of the 27 patients with primary osteosarcoma of flat bones died of their tumor; an additional patient died of doxorubicin-related cardiomyopathy and had microscopic disease in the primary site at autopsy. Thirteen of the 18 patients with secondary osteosarcoma died of their second metastatic cancer, 2 additional patients died of doxorubicin-related cardiomyopathy/coccidioidomycosis, and another of acute renal toxicity.

Adolescent↗

Second malignant neoplasms occuring in survivors of osteosarcoma.

BACKGROUND: Second malignant neoplasms have been noted infrequently in survivors of osteosarcoma treated before 1970. METHODS: For the above reason, the authors surveyed their patients to determine the actuarial incidence and relative risk of second malignancies among patients treated with adjuvant chemotherapy for osteosarcoma. RESULTS: Between March 1962 and March 1996, 334 patients received chemotherapy for newly diagnosed primary or metastatic osteosarcoma. Of these patients, 47 presented with metastases, 14 had multifocal osteosarcoma, and 273 had localized disease. Nine patients developed second malignant neoplasms 0.45-17.8 years (median, 6.3 years) after receiving definitive surgery and adjuvant chemotherapy for primary osteosarcoma; 2 of these patients had pulmonary metastasectomies before receiving adjuvant chemotherapy. The second neoplasms comprised two cases of malignant fibrous histiocytoma and one case each of melanoma, glioblastoma multiforme, chondrosarcoma, and carcinoma of the breast: stomach, colon, rectum. The overall 10-year cumulative incidence of second malignancies was 2% +/- 1%; by comparison, this rate was 2% +/- 1% for patients with localized osteosarcoma but was 8% +/- 5% (P = 0.15) for those who presented with metastatic disease. CONCLUSIONS: Since the advent of successful adjuvant chemotherapy, more patients are surviving primary osteosarcoma; therefore, the number of osteosarcoma patients who develop second malignancies can be expected to increase. Recognition of osteosarcoma patients who are members of families with Li-Fraumeni syndrome may lead to earlier intervention for these individuals.

Adolescent↗

Brain metastases in children with melanoma.

BACKGROUND: Brain metastases complicate the course of malignant melanoma in at least 20% of adult cases. These events are commonly preceded by metastases to other sites. Due to the rarity of malignant melanoma in children, little is known about the incidence, clinical features, and outcome of children with melanoma who develop brain metastases. METHODS: The authors reviewed the records of 44 children with malignant melanoma treated at St. Jude Children's Research Hospital over a 33-year period. Eight (18%) developed brain metastases during the course of their disease. The authors reviewed the clinical and radiologic features of six of these cases, for whom complete clinical information and imaging studies were available. RESULTS: The median age at diagnosis of malignant melanoma was 15 years (range, 11-21 years). Brain metastases developed a median of 20 months (range, 0-50 months) after diagnosis and were preceded by metastases to other organs in 5 patients. In most cases, lesions were supratentorial and multiple. Most showed radiologic signs of intralesional hemorrhage. All patients received whole brain radiotherapy, and one had surgical resection. Three patients received chemotherapy. Five patients died a median of 5 months (range, 2-10 months) after diagnosis of brain involvement. One patient, who had a single brain metastasis at diagnosis, is alive more than 34 months later. CONCLUSIONS: Brain metastases develop in a significant proportion of children with malignant melanoma and are associated with a poor outcome. The incidence, features, and outcome in children do not appear to differ from those in adults.

Adolescent↗

Phase I trial of subcutaneous interleukin-1 alpha in children with malignant solid tumors.

Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models of cancer chemotherapy and is similarly beneficial in adults treated with carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation. There are no trials of this agent in children. Our purpose was to determine the toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3, carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL-1 alpha before either the first or second course of therapy. After the MTD of rhuIL-1 alpha was determined an additional group of patients received rhuIL-1 alpha at the dose immediately following ICE chemotherapy. The dose-limiting toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day. There were no differences in chemotherapy-induced hematologic toxicity with increasing doses of rhuIL-1 alpha or in comparisons before or after ICE chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving myelosuppressive chemotherapy, clinical usefulness would mandate a significant hematopoietic benefit in view of the trouble some side effects identified. We saw no evidence of a hematoprotective effect.

Adolescent↗

Soft tissue sarcoma of the hand in children: clinical outcome and management.

Soft tissue sarcomas (STS) of the hand are rare in children and adolescents. From 1965 through 1995, 18 children with STS of the hand were treated at our institution. Rhabdomyosarcoma (RMS) was diagnosed in 11 patients; alveolar histological results predominated (7 of 11 cases). Seven patients presented with metastatic disease and died 4 to 23 months (median, 9 months) from diagnosis; their surgical treatment comprised above-elbow amputation (n = 1), local excision (n = 1), and biopsy (n = 5). For the four patients who presented with localized RMS, surgery consisted of wide local excision (n = 1), local excision (n = 2), or ray amputation (n = 1). With an average follow-up of 5.5 years (range, 4 months to 18 years), 3 of the 11 patients diagnosed with RMS still survive (27%). The remaining seven patients presented with nonrhabdomyosarcomatous soft tissue sarcoma (NRSTS); the most common histological variants were epithelioid and malignant fibrous histiocytoma (two cases each). Surgical treatment for these patients comprised ray amputation (n = 3), wide local excision (n = 3), excisional biopsy (n = 1), and regional lymph node dissection (n = 3). One patient received adjuvant multiagent chemotherapy; three patients received supplemental radiotherapy. Six of the seven (85%) patients are alive with no evidence of disease at an average follow-up of 4.7 years (range, 6 months to 12 years).

Child↗

Complications of pelvic exenteration in children who have genitourinary rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma is the most frequently encountered soft tissue sarcoma in children younger than 15 years of age. METHODS: The authors reviewed the early and long-term morbidity rate and clinical outcome of pelvic exenteration for genitourinary rhabdomyosarcoma (GU-RMS) in children. Of 43 patients with this diagnosis who were seen at St Jude Children's Research Hospital between 1963 and 1994, 17 underwent pelvic exenteration. These 13 boys and four girls ranged in age from 6 months to 15 years (median, 3.5 years). Their primary sites included prostate (n = 12), bladder (n = 4), and uterus (n = 1). All patients received multiagent chemotherapy and either preoperative or postoperative radiation therapy. Anterior exenteration was performed in 15 patients and total exenteration in two. The complications were classified as early or late (occurring within or after 30 days from the date of surgery) and as major or minor (depending on the risk of death or physical or functional disability). RESULTS: Thirteen of the 17 patients (76%) had 49 surgery-related complications. Wound infection (24%), fistula, abscess, and malnourishment (12% each) were the most common early major complications, with hydronephrosis (35%), bowel obstruction (24%), acute pyelonephritis, fistula, lymphedema, and ureter stenosis (12% each) making up the majority of late complications in this category. Relatively frequent minor complications included protracted paralytic ileus and hematuria (18%), cholelithiasis, chronic diarrhea and, peristoma skin irritation (12%). Disease-free survival was associated with the timing of surgery (P = .002). All but one of the 12 patients who underwent surgery within 6 months of diagnosis are alive, compared with only one of five whose surgery was performed after a longer interval. Pelvic exenteration for GU-RMS was associated with a high rate of serious complications in this series of patients treated over 31 years. CONCLUSION: With recent advances in surgical techniques, as well as improvements in preoperative and postoperative care, this procedure should continue to be applied in cases resistant to conventional therapy.

Adolescent↗

Orbital development in long-term survivors of retinoblastoma.

PURPOSE: To determine the effects of enucleation, irradiation, and age at diagnosis on bony orbital growth in long-term survivors of retinoblastoma using measurements based on computed tomographic (CT) imaging. PATIENTS AND METHODS: We used CT obtained at a median age of 13 years to measure orbital volume and configuration in 54 patients who had been treated for retinoblastoma a minimum of 5 years previously. RESULTS: Enucleation and high-dose orbital irradiation (> 35 Gy) both independently adversely affected orbital development (P = .014 and P = .022, respectively). Orbital volume differences for children treated when < or = 1 year old were no greater than those for children treated when older than 1 year of age. In children treated for bilateral retinoblastoma, the impact of enucleation on orbital development was not statistically different from that of irradiation (P = .13). Small implants (12 to 14 mm in diameter) were more commonly associated with smaller orbital volumes. Migration of orbital implants was associated with the smaller orbital sphere size in children < or = 1 year of age (P < .035). CONCLUSION: Treatment for retinoblastoma compromises orbital development. Resulting orbital asymmetry seems to be at least partially related to the size of the implant. Detailed imaging-based measurements of orbital volume and configuration may aid the planning for cosmetic and reconstructive surgery in those who develop orbital asymmetry.

Age Factors↗

Michigan physicians' perceptions of their role in managing obesity.

In a random sample of 211 primary-care physicians in Michigan, about 33% (n = 70) perceived their role in the prevention of obesity as coordinating and 39% (n = 82) as cooperative and of equal importance to that of other professionals. Perceived barriers to prevention of obesity were inadequate time to educate patients, method of reimbursement, and inadequate training in management of obesity. These results suggest that physicians' involvement in managing obesity can improve if they work closely with other health professionals.

Adult↗

Alveolar soft part sarcoma in children and adolescents: clinical features and outcome of 11 patients.

The clinical features and response to therapy of pediatric alveolar soft part sarcoma, a rare soft tissue sarcoma of uncertain histogenesis, have not been previously described in detail in the literature. We retrospectively reviewed the clinical characteristics of all patients with alveolar soft part sarcoma who were seen at our institution over a 32-year period. We found 11 patients with the diagnosis of alveolar soft part sarcoma. Their ages ranged from 2.8-16 years (median 9.8). Staging was determined using the Intergroup Rhabdomyosarcoma Study clinical grouping system and the UICC TNM system. Accordingly, there were six patients with grossly resected tumors (clinical groups I and II) and five with unresected or metastatic disease (clinical groups III and IV). Children with resected disease were more likely to have smaller noninvasive tumors. The main feature predictive of survival was tumor resectability, since chemotherapy in various combinations failed to produce significant tumor responses. Nine patients are disease-free with a median follow-up of 11.9 years. Surgical resection remains the mainstay of therapy for pediatric alveolar soft part sarcoma. Since active chemotherapy agents have not been identified, patients with unresected or metastatic disease may benefit from experimental agents. The survival rate of this cohort is superior to that seen in adults.

Adolescent↗

Outcome in 43 children presenting with metastatic Ewing sarcoma: the St. Jude Children's Research Hospital experience, 1962 to 1992.

The purpose of this work was to review the St. Jude Children's Research Hospital experience of patients presenting with metastatic Ewing sarcoma over a 30-year period. Forty-three of 212 cases of Ewing sarcoma presented with metastases at diagnosis. These patients were analyzed to determine whether primary tumor site or size, metastatic site(s), or advances in therapy have had a positive impact on survival. The overall survival for our 43 patients was 35% (95% confidence intervals, 20% to 50%). Comparing patients treated prior to 1979 with those treated after 1979, the overall survival was significantly different (P = 0.0002). Comparing overall survival between pelvic and non-pelvic primaries (P = 0.24), among metastatic sites (P = 0.83), and between tumors measuring > 8 cm in diameter to tumors measuring < 8 cm in diameter (P = 0.12), no significant differences were observed. Approximately one-third of patients presenting with metastatic Ewing sarcoma may achieve long-term survival. Children with metastatic Ewing sarcoma may benefit from clinical trials which intensify the doses of doxorubicin, and the highly effective combination of ifosfamide/etoposide.

Antineoplastic Combined Chemotherapy Protocols↗

Role of irradiation in management of synovial sarcoma: St. Jude Children's Research Hospital experience.

The role of irradiation in the management of synovial sarcoma (SS) in pediatric patients is evaluated. The review covers all children seen at St. Jude Children's Research Hospital between May 1969 and December 1992 with the diagnosis of soft tissue sarcoma, of the 37 patients with the subtype SS, 16 received irradiation for the management of primary site disease. There were four IRS Group I, six Group II, four Group III, and two Group IV patients receiving irradiation. Tumor grade included seven Grade II, and nine Grade III lesions. TMN staging identified eight T1 and eight T2 lesions. Follow-up has ranged from 14 to 117 months (med = 33 months). All IRS Group I patients had documented local control. Five of six IRS Group II and 4/4 Group III patients have had documented local control at last follow-up. IRS Group IV patients had either local control tumor stabilization (n=1) or evidence of tumor regression (n=1) at autopsy. Complications following irradiation include wound dehiscence (n=1), surgery to revise a painful scar (n=1) extremity length discrepancy (n=2), and femoral head avascular necrosis (n=1). At last follow-up, 10 of 14 patients receiving curative intent irradiation remain alive. This review indicates questionable benefit to the addition of irradiation for patients with adequate surgical resection and having "good" tumor characteristics (Grade I, II; IRS Group I, TMN T1A,T1B. For lesions that have had incomplete resection or partial response to chemotherapy, there is evidence that irradiation may provide durable local control. The role of irradiation in those patients with IRS Group IV disease is at present confined to palliative roles until the time when more effective chemotherapy will mandate the decision to treat primary disease for curative measures.

Adolescent↗

Treatment outcome and dose-response relationship in infants younger than 1 year treated for retinoblastoma with primary irradiation.

Thirty-three infants ( < 1 year at diagnosis) were treated for retinoblastoma with primary irradiation at St. Jude Children's Research Hospital (SJCRH) between 1963 and June 1992. Staging of the 44 treated eyes was as follows: Reese-Ellsworth (R-E) Groups I (n = 20), Group II (n = 9), Group III (n = 6), Group IV (n = 2), Group V (n = 7). Irradiation was delivered using either a single anterior field (31 eyes) or lens-sparing techniques (13 eyes). Total doses ranged from 21-45 Gy (median = 36 Gy) in fractions of 150-180 cGy (n = 34) or > 180 cGy (n = 10). One child died of metastatic disease at 42 months. Three patients have developed second malignant neoplasms; two have succumbed at 88 and 125 months post-RB diagnosis; the remaining patients are alive at 6-259 months postdiagnosis (median follow-up = 127 months). Local control with irradiation alone and supplemented cryotherapy given within 2 months (n = 2) was maintained in 29 eyes, with no statistical difference seen for total doses < or = 36 Gy (21/8 eyes) vs. > 36 Gy (8/16). Of 15 eyes that required salvage therapy, tumor control has been maintained in 13. Enucleation was required for four patients, two with recurrent retinoblastoma and one with a phthisical eye. Cataract formation was documented in 23 eyes (87.5%) treated with lens-sparing techniques developed cataract. At last follow-up, 23 of 30 patients tested (77%) had visual acuity of 20/100 or better. This experience confirms early observations in that doses > or = 36 Gy do not appear to improve local control with irradiation alone in infants ( < 365 days) with retinoblastoma.

Cryotherapy↗

Response of pediatric malignant solid tumors following ifosfamide or ifosfamide/carboplatin/etoposide: a single hospital experience.

One hundred thirty-eight pediatric patients have received treatment for malignant solid tumors with ifosfamide with mesna, and 71 have received a combination with ifosfamide/carboplatin/etoposide (ICE). Responses were obtained in many types of pediatric tumors, yet comparison of responses was not possible because of inadequate numbers of tumors of differing histiotypes. Comparison of results between patients with all tumors treated with ifosfamide or ICE indicated that there was a higher response rate for patients treated with ICE, with an estimated odds ratio of 2.74 (95% C.I. 1.45-5.179). Excluding patients without prior chemotherapy and radiotherapy, the odds ratio for 2.801 (95% C.I. 1.45-5.4) suggests a similar result. There remain no guarantees that the more costly treatment with ICE, which requires cytokine support, will offer therapeutic benefits against resistant solid tumors.

Antineoplastic Agents, Alkylating↗

Topoisomerase I interactive drugs in children with cancer.

Topotecan, irinotecan, and 9-aminocamptothecin (9-AC) are analogs of the plant alkaloid 20(S)-camptothecin (CMT), the prototypical DNA topoisomerase I interactive agent. These agents interact with the topoisomerase I-DNA complex and prevent resealing topoisomerase I-mediated DNA single-strand breaks. This eventual leads to double-strand DNA breaks and apoptosis or cell death. Topotecan, irinotecan, and 9-AC have shown significant activity in mice bearing pediatric solid tumor xenografts; the greatest antitumor responses were found with protracted continuous schedules. Preclinical data also suggest that maintenance of an exposure-duration threshold (EDT) may be required to achieve optimal cytotoxicity. Pediatric Phase I trials have evaluated the toxicity and safety to camptothecin analogs in children with relapsed solid tumors and relapsed acute leukemia. The primary dose-limiting toxicity (DLT) for the CMT analogs in children has been myelosuppression, except for mucositis observed with the 120-hr continuous topotecan infusion schedule. Pharmacodynamic relationships with these analogs have been reported between systemic exposure, and myelosuppression and mucositis. Although not a primary objective of the early Phase I studies, antitumor responses have been reported. In this review, the pharmacokinetic and pharmacodynamics of the CMT analogs studied in children are summarized, and future studies of these agents are discussed.

Animals↗

Malignant melanoma in children: imaging spectrum.

OBJECTIVE: The objective of this study was to investigate the role of diagnostic imaging in detecting unsuspected metastatic disease in children with malignant melanoma. This has not been well studied previously. MATERIALS AND METHODS: We correlated imaging findings of 33 children diagnosed with melanoma with the level of invasion and clinical stage of disease. RESULTS: Clinically undetectable metastases were identified in eight patients (25 %), four of whom had multiple metastases. All eight patients had deep lesions (Clark's level IV or V) or unknown primary sites of disease. CONCLUSION: Children with thick melanomas and those with unknown site of primary tumors are at increased risk of having clinically unsuspected metastases and should undergo CT of the chest, abdomen, and local-regional nodal basins at diagnosis to determine disease extent.

Abdominal Neoplasms↗