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Biomedical subjects

I D Fleming

Publications and source records attributed to I D Fleming.

At least 37 records · Page 2Linked to original sources

Pediatric brachytherapy. The St. Jude Children's Research Hospital experience.

BACKGROUND: The use of interstitial, intracavitary, and permanent placement of radioactive isotopes has become a common practice in adult oncology patients based on numerous reports indicating improved local control and survival when used. These same irradiation techniques and treatments have been infrequently used for children with malignant disease despite known dose localization properties that allow for highly focal irradiation delivery with rapid reduction of the dose in nearby normal tissues. The noted benefit of decreased late complications noted in the adult series is also attractive, especially when considering the treatment of children. METHODS: Between May, 1981 and December 15, 1992, 46 children with non-CNS primary malignancy received 50 brachytherapy applications for primary therapy (n = 11 sites), as a boost in conjunction with external beam irradiation (n = 16 sites), or as treatment of recurrent disease or a second malignant neoplasm in a previously irradiated region that precluded further external irradiation or for metastatic disease (n = 23 sites). The most common tumor histologies were rhabdomyosarcoma (n = 14), soft tissue sarcoma (n = 10) and retinoblastoma (n = 10). Patient age at implantation ranged from 8 weeks to 24 years; follow-up maintained in all patients and has ranged from 2-115 months (median, 39 months). RESULTS: Forty-three of 50 sites receiving brachytherapy have maintained continuous disease free intervals, ranging from 2 to 115 months postimplantation (median, 41 months). The seven local failures occurred 2-20 months postimplant (median, 6 months). Severe complications occurred in 12 patients, two which were life threatening but resolved without further incident. CONCLUSIONS: Based on this ongoing clinical investigation, the authors recommend brachytherapy for selected pediatric malignancies and continue to evaluate the various factors associated with local control, local failures, and complications.

Adolescent↗

Primary malignancy of the salivary gland in children.

Seventeen pediatric patients with a major salivary gland malignancy (16 parotid, 1 submaxillary) were reviewed. Eight patients presented with carcinoma. The usual presentation was a mass over the affected gland. Six patients had localized disease, which was treated by excision. This was accomplished by either a total or subtotal parotidectomy or resection of the submaxillary gland. Two patients received adjuvant radiation therapy. All six patients with localized carcinoma are alive, without evidence of disease. Two patients presented with metastatic disease and died of the disease despite treatment with multiagent chemotherapy, and in one case, radiation therapy. Nine patients had rhabdomyosarcoma (RMS). The usual presentation was a mass at the angle of the mandible. Five patients had involvement of one or more cranial nerves, and two had concomitant cervical adenopathy. Eight patients had a biopsy and then were treated according to an existing prospective institutional protocol. The ninth patient initially underwent a superficial parotidectomy. Seven patients received radiation therapy. In one patient, rapid progression of the disease precluded this treatment. Seven patients died of progressive local and distant disease 2 months to 2 years (median, 6 months) from the time of diagnosis. Two patients are alive, without evidence of disease, 3 and 7 years after presentation. We conclude that carcinoma should be managed with complete excision. For RMS of the salivary gland, a biopsy should be performed, and treatment should consist of chemotherapy and radiation therapy.

Adolescent↗

Breast malignancy in children.

In 25 years, 18 patients with breast cancer were treated at St Jude Children's Research Hospital, 16 were female and 2 were male. The patients presented with primary malignancy (2), metastatic disease (13), or secondary malignancy (3). One of the females with primary breast malignancy had alveolar rhabdomyosarcoma. She was treated with wide excision and is currently receiving chemotherapy. The other patient presented with non-Hodgkin's lymphoma of the right breast. After biopsy, she was treated with chemotherapy. Of 13 patients with metastatic disease, the primary lesion was rhabdomyosarcoma in nine. One patient each had non-Hodgkin's lymphoma, Hodgkin's lymphoma, neuroblastoma, and signet-cell adenocarcinoma. All patients with metastatic disease to the breast died of the disease. Three females presented with invasive ductal carcinoma of the breast after treatment for Hodgkin's disease. Two underwent mastectomy and are alive without evidence of disease. One patient refused therapy and died of the second malignancy. We conclude that (1) breast malignancies had three distinctly different presentations in our patients, (2) the breasts of pediatric oncology patients should be carefully and routinely examined for metastatic disease, and (3) metastatic disease in the breast of a child is a manifestation of disseminated disease and is associated with an extremely poor prognosis.

Adolescent↗

Carcinoembryonic antigen and carbohydrate 19-9 antigen as markers for colorectal carcinoma in children and adolescents.

Colorectal cancer is rare in patients younger than 20 years of age (incidence, 1 in 10 million). Although carcinoembryonic antigen (CEA) and carbohydrate 19-9 antigen (CA 19-9) have been used widely as markers for the efficacy of therapy or detection of recurrent colorectal carcinomas in adults, no studies evaluating their efficacy in children and adolescents have been performed. Between 1986 and 1989, serial measurements of serum CEA and CA 19-9 levels were obtained from 11 patients (aged 8 to 18 years) treated at the institution of the authors. In contrast to the experience in adults, most (9 of 11) of the tumors were localized in the right or transverse colon. Histologically, 10 of 11 carcinomas were mucinous. Most patients had either Dukes' C (5 of 11) or D (5 of 11) lesions. After surgery, all patients were treated with a combination of 5-fluorouracil with Leucovorin (Lederle Laboratories, Pearl River, NY). With the use of the adult normal standards (CEA less than 3.0 ng/ml and CA 19-9 less than 37 ng/ml)6 for the patients, the specificity and sensitivity of CEA were 77% and 64%, respectively, whereas the specificity of CA 19-9 was 79% and the sensitivity was significantly low (10%). The combined specificity of the two markers was 71%, and the combined sensitivity was 60%. On the basis of these results, the authors believe that CEA and CA 19-9 are not effective markers for detection of recurrent or progressive colorectal carcinomas in children and adolescents.

Adenocarcinoma, Mucinous↗

Pediatric nonrhabdomyosarcomas of the extremities. Influence of size, invasiveness, and grade on outcome.

Surgery alone or supplemental radiation is effective in local control in a majority of patients with nonrhabdomyosarcoma of the soft tissue. To determine the factors influencing subsequent survival, a retrospective review of 64 children with nonrhabdomyosarcoma of the soft tissue of the extremities was performed. Using the American Joint Committee on Cancer staging system, 32 patients had noninvasive T1 lesions, and 31 of these patients survived disease free. Twenty-two patients had lesions that were smaller than 5 cm; 19 of these lesions were grade G1-2. All 22 patients survived. Ten patients had tumors that were 5 cm or larger, and all were G1-2; nine of these patients survived. Thirty-two patients had invasive (T2) lesions; seven of these lesions were smaller than 5 cm, but four were G3. Only one patient survived. Eighteen (72%) of 25 lesions that were 5 cm or larger were G3. Fifteen (83%) of these 18 patients underwent relapse, with 12 patients dying of the disease. Important prognostic factors included G3 lesions, with a 72% (18 of 25 patients) failure rate, and T2 lesions, which were generally larger than 5 cm, of higher grade, and underwent relapse more frequently than T1 lesions. These patients with histologic G3 and T2 lesions may benefit from chemotherapy.

Adolescent↗

Sarcomas (other than Ewing's) of flat bones in children and adolescents. A clinicopathologic study.

The clinicopathologic features and response to therapy of 28 patients with non-Ewing's flat bone sarcoma treated at St. Jude Children's Research Hospital, Memphis, Tennessee, over a 25-year period were reviewed. Twenty-two patients had osteosarcoma, four malignant fibrous histiocytoma, one chondrosarcoma, and one fibrosarcoma. Ages at diagnosis ranged from 3 to 24 years (median, 15 years). Primary sites were craniofacial bones in ten patients, pelvis eight, scapula four, ribs two, metatarsal bones two, clavicle one, and vertebra one. All primary tumors were associated with soft tissue extension; none of the patients had metastatic disease at presentation. Six cases represented second malignancies that arose 5 to 16 years after irradiation for an unrelated tumor. Complete excision was possible in ten patients, eight of whom received postoperative chemotherapy. Five of these patients remain free of disease 1.8+ to 13+ years (median, 8.1 years) from diagnosis. Prolonged remissions after adjuvant chemotherapy were achieved in only two of 18 patients after incomplete surgical resection or biopsy. The median survival time in this group was 1 year (range, 0.2-7.7+ years). The remaining 16 patients had progressive local disease, but only two developed concurrent metastases. Thus, complete surgical resection appears to maximize disease-free survival in patients with non-Ewing's flat bone sarcoma. For the large percentage of patients in whom total resection is not possible, because of soft tissue extension and local invasion of bulky tumors, preoperative chemotherapy may increase the likelihood of complete excision and improve long-term survival.

Adolescent↗

Adjuvant chemotherapy for osteosarcoma of the extremity. Long-term results of two consecutive prospective protocol studies.

Seventy-six patients with classic high-grade osteosarcoma of an extremity received adjuvant chemotherapy by two protocols, initiated in 1972 and 1977, respectively, after appropriate amputations. Chemotherapy consisted of high-dose methotrexate, doxorubicin, and cyclophosphamide. Dose intensity of high-dose methotrexate and doxorubicin was greater for the patients treated with the protocol initiated in 1977. The proportion of long-term disease-free survivors on the two protocols are 46% and 56%. A better outcome (P = 0.042) was seen for the latter group, which received more intensive chemotherapy. Overall, metastases developed in 35 patients; in 19 who were receiving chemotherapy and in 16 after chemotherapy. The outcome for these two protocols, compared with two control groups that were given no chemotherapy or ineffective chemotherapy (biweekly vincristine and cyclophosphamide), confirms the results of controlled studies that showed an advantage of adjuvant chemotherapy after amputation for osteosarcoma.

Adolescent↗

Surgical implications of primary gastrointestinal lymphoma of childhood.

Our purpose was to summarize information from a large single institution's experience regarding the role of surgical resection in the management of non-Hodgkin's lymphoma in children and adolescents. Fifty-eight children were treated for primary gastrointestinal non-Hodgkin's lymphoma. The tumors usually presented in the ileocolic region (n = 54). Twenty-one children presented with intussusception. Complete surgical resection of tumor was accomplished in 32 patients, partial resection in 20, and biopsy only in 6. All patients were given lymphoma protocols employing chemotherapy and irradiation. Forty-four (76%) of 58 patients are surviving from 1 year to greater than 20 years from diagnosis. Thirty-one of 32 patients who underwent complete resection followed by protocol management are surviving, compared with 13 of 26 children with residual gross disease. The results indicate that children with primary gastrointestinal non-Hodgkin's lymphoma benefit from complete surgical resection when feasible.

Adolescent↗

Malignant melanoma in children: its management and prognosis.

Malignant melanoma is rare in children, representing 1% to 3% of all pediatric malignancies. Thirty-three children with malignant melanoma were treated at St Jude Children's Research Hospital from 1967 to 1988. Their ages ranged from 1 day to 20 years (median, 12 years); 23 were boys and 10 were girls; and 5 of the 33 (15%) were black. Four of the 33 children had been treated for a previous malignancy. In 3, melanoma arose within a bathing trunk nevus. The extremity was the most common site (13), followed by the trunk (9), head and neck (7), and perineum (1). In 3 patients the primary site could not be determined. Upon initial presentation to St Jude Hospital, 17 patients had localized disease (stage I), 10 had regional node involvement (stage II), and the remaining 6 patients had disseminated disease (stage III). Using both Clark's level and Breslow's thickness as indicators, the incidence, initial stage, prognosis, and survival were compared. By Clark's level, 7 patients, (6 of whom were stage I) were level II or III, and 22 patients were level IV or V. Though 16 of 22 level IV and V patients were initially stage I, 10 patients eventually developed progressive disease. Similar observations were noted when using Breslow's thickness to evaluate the primary. In 5 of 27 evaluable patients, Breslow's depth of invasion was less than 1.5 mm. All 5 of these patients were diagnosed with stage I disease and have not shown progressive disease.

Adolescent↗

Multidisciplinary treatment planning. Tumor boards.

A brief review of the current status of cancer treatment based on hospital consultations, cancer treatment plans, and cancer management protocols is presented. Some potential for the development of clinical indicators around these various consultation activities are explored. The utilization of hospital tumor conference and tumor boards as a mechanism for multidisciplinary treatment planning and consultation is reviewed and possible utilization of a measure of such activities as potential clinical indicators is presented.

Female↗

Management and prognosis of head and neck sarcomas.

Between 1962 and 1988, a total of 104 patients with head and neck rhabdomyosarcoma (RMS) and 17 patients with nonrhabdomyosarcoma (NRMS) were evaluated and treated at St. Jude Children's Research Hospital. All parameningeal sites (middle ear, orbit, or nasopharynx) were excluded from further analysis; thus, 50 patients represent the cohort of head and neck sarcomas for this review. Survival was good in this group of patients, 28 of 50 being alive and disease-free at last follow-up. Twenty of the 38 patients with RMS were alive and disease-free. Similarly, 8 of the 12 patients with NRMS were disease-free at a median follow-up of 5 years. However, the site and size of the primary tumor impacted on the extent of the initial resection and further treatment in addition to surgery. Although the treatment policy evolved over time to a stage-specific strategy for treatment modalities, the data suggest that surgery alone may be sufficient initial therapy for a subset of patients. For patients in whom complete resection is not achieved, the addition of radiotherapy and chemotherapy may result in improved survival.

Adolescent↗

Chest wall resection for Ewing's sarcoma of the rib: an unnecessary procedure.

Approximately 10% of all cases of Ewing's sarcoma arise from a rib. Conventional management has included chest wall resection (3 or more ribs) and radiation therapy. These forms of therapy have led to complications such as scoliosis and local deformity. The addition of radiation therapy can result in damage to the lung and adjacent viscera and also potentiate pulmonary restrictive disease. Between 1971 and 1978, 9 patients were treated with surgery, radiation therapy, and combination chemotherapy (three- or four-drug regimen). Only 2 patients (22%) survive. Since 1979, 14 patients were entered into a new protocol consisting of sequential induction chemotherapy, followed by delayed surgical resection whenever feasible. Three patients had complete resection of their primary lesion at onset. Initially, 7 patients had either biopsy (N = 4) or incomplete chest wall resection N = 3). All 4 patients with biopsy only at diagnosis had excellent responses to induction chemotherapy, allowing delayed resection of the involved rib without chest wall resection. Overall, 12 of 14 patients (86%) treated since 1979 survive, with only 2 receiving radiation therapy for residual disease in the primary rib site.

Adolescent↗

Challenges in the treatment of childhood fibromatosis.

Between 1968 and 1985, we treated 20 children for fibromatosis (also called desmoid tumor and aggressive fibromatosis). The primary sites included head and neck (seven patients), extremity (seven patients), and trunk (six patients). Lesions ranged from 3 to 18 cm in diameter. The tumors were smaller than 5 cm in 13 patients, and in seven patients they were larger than 5 cm. A total resection was not feasible in any of the patients with lesions larger than 5 cm. Ten of the 11 patients treated with wide local resection, in whom the margins were clearly negative or close, remained free of disease for six to 16 years. Nine patients required additional treatment with radiotherapy (nine patients) and chemotherapy (five patients). Two died of local disease progression. In the remaining seven children, the disease was controlled. We describe our strategies for managing this disease in a pediatric population.

Adolescent↗