Delavirdine in combination with zidovudine in treatment of human immunodeficiency virus type 1-infected patients: evaluation of efficacy and emergence of viral resistance in a randomized, comparative phase III trial. The M/3331/0013B Study Group.

We compared the activity of delavirdine (DLV) plus zidovudine (AZT) (n = 300) with that of AZT (n = 297) against human immunodeficiency virus type 1 in a randomized, double-blind, placebo-controlled trial. DLV exerted a transient antiviral effect, and mutations for resistance to DLV were found in more than 90% of subjects at week 12. The K103N mutation, which confers nonnucleoside reverse transcriptase inhibitor cross-resistance, was found in 85% of the patients.

CNS involvement in children with newly diagnosed non-Hodgkin's lymphoma.

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin's lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance. PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P =. 095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease. CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.

Chemotherapy dose-intensification for pediatric patients with Ewing's family of tumors and desmoplastic small round-cell tumors: a feasibility study at St. Jude Children's Research Hospital.

PURPOSE: To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors. PATIENTS AND METHODS: From February 1992 to June 1996, we treated 53 consecutive patients on our Ewing's protocol. Induction comprised three cycles of ifosfamide/etoposide on days 1 to 3 and cyclophosphamide (CTX)/doxorubicin on day 5, followed by granulocyte colony-stimulating factor. Local control using surgery and/or radiotherapy started at week 9 along with vincristine/dactinomycin. Maintenance included four alternating cycles of ifosfamide/etoposide and doxorubicin/CTX, with randomization to one of two CTX dose levels to determine the feasibility of dose-intensification during maintenance. RESULTS: Patients had a median age of 13.4 years (range, 4.5 to 24.9 years); 34 patients were male and 43 patients were white. Nineteen patients presented with metastatic disease, 29 had tumors greater than 8 cm in diameter, and 26 had primary bone tumors. These patients received 155 induction cycles, 91% of which resulted in grade 4 neutropenia, 68% in febrile neutropenia, and 68% in grade 3 to 4 thrombocytopenia. During maintenance, grade 4 neutropenia and grade 3 to 4 thrombocytopenia occurred in 81% and 85% of cycles, respectively. Thirty-five patients (66%) completed all therapy, only 13 without significant delays; three developed secondary myeloid malignancies. The toxicity and time to therapy completion were similar in both CTX arms. Estimated 3-year survival and event-free survival were 72%+/-8% and 60%+/-9%, respectively. CONCLUSION: Although intensifying therapy seems feasible for 25% of patients on this study, toxicity was considerable. Therefore, the noninvestigational use of dose-intensification in patients with EFT should await assessment of its impact on disease-free survival.

Hyperostosis frontalis interna: an anthropological perspective.

Hyperostosis frontalis interna (HFI) is manifested by the accretion of bone on the inner table of the frontal bone. Despite the vast literature on HFI, ambiguity exists as to its etiology, osteogenesis, demography, and history. This stimulated the present broad-scale study of HFI which included the evaluation of 1,706 early 20th century skulls (1,007 males and 699 females) from the Hamann-Todd and Terry human osteological collections, as well as 2,019 pre-19th century East-Mediterranean, Amerindian, and Central European skulls. In addition, 72 cadavers were dissected for gross inspection and histology. Special attention was paid to the relationship of the brain and meninges to endocranial lesions. HFI is an independent condition, not a symptom of a more generalized syndrome as suggested in the past. It can appear in a variety of forms but each is the result of the same process and probably of the same etiology. Investigators' previous failure to recognize the mild stages of HFI (types A and B) as an early form of the general HFI process led to erroneous statistics and interpretations of observations. HFI should also be considered a phenomenon separate from HCI, hyperostosis cranialis diffusa (HCD), and other endostoses, even when it appears in association with them. To avoid ambiguity and facilitate the description of cranial hyperostoses, uniform nomenclature (HFI, HCD) has been recommended. HFI is rarely seen in historic populations, regardless of geographical origin. It is most commonly found among females and is believed to be associated with prolonged estrogen stimulation. While its magnitude of manifestation and frequency are much higher in females, HFI is not a purely female phenomenon. Males with hormonal disturbances such as atrophic testis were found to manifest HFI type D. HFI is associated with age insofar as it is much less frequent in females under 40 years of age. Although advanced cases of HFI (types C and D) have been observed in individuals as young as 40 years of age, it is more frequently found after age 60. The frequency of HFI type D will not increase from age 60. Type-predicted analysis by cohort reveals significant ethnic differences. Changes in African American (AA) females appear earlier in life and progress more rapidly than in European American (EA) females. Analysis of radiographs shows a discrepancy between the anatomic prevalence of HFI and its radiological recognition, which is very poor for mild cases. This apparently resulted in the misconceptions that HFI is entirely an old-age phenomenon, and that it is exclusively female. Histological analysis shows that the inner table along with the closely attached dural layer play a major role in the osteogenesis of HFI. Contrary to previous models, no evidence for diploe or ectocranial plate involvement was found. Cadaver study suggests that the predilection for the frontal area may be related to an altered blood supply and/or vascular stretching.

Late effects of treatment for germ cell tumors during childhood and adolescence.

PURPOSE: To evaluate the long-term sequelae of treatment for malignant germ cell tumors (GCT) during childhood and adolescence. PATIENTS AND METHODS: Of 128 patients treated for GCT at St. Jude Children's Research Hospital between 1962 and 1988, 73 are long-term survivors (continuously disease-free for > or =5 years after diagnosis), with a median follow-up of 11.3 years). Survivors' ages at diagnosis ranged from birth to 18.3 years (median, 9.2 years); 64% (47 patients) were female. Initial surgical resection was followed by observation for stage I germinomas (n = 2), testicular tumors (n = 13), and selected cases of ovarian or sacrococcygeal tumors (n = 2), and by radiation therapy (RT) for patients with stage II to III germinoma (n = 8). The remaining 48 patients received postoperative chemotherapy (vincristine, dactinomycin, and cyclophosphamide [VAC] +/- doxorubicin, 1962 to 1978; VAC and/or cisplatin, vinblastine, and bleomycin [PVB], 1979 to 1988). RT was added to the chemotherapy for 21 patients. Late complications involving various organ systems and their relationship to treatment were evaluated. RESULTS: More than two-thirds of long-term survivors (n = 50) had at least 1 complication, and half (n = 38) had > 1 organ system affected. The systems most often involved included the musculoskeletal (41% of survivors), endocrine (42%), cardiovascular (16% excluding those who had only abnormal chest radiograph), gastrointestinal (25%), genitourinary tract (23%), pulmonary (19%), and neurologic (16%) systems. High-frequency hearing loss occurred in 58% (11 of 19) of patients treated with cisplatin. Musculoskeletal, gastrointestinal, and urinary tract abnormalities were most frequent in patients whose treatment included RT. CONCLUSIONS: A high frequency of late effects after treatment for pediatric GCT, particularly in patients who received RT, was demonstrated. Treatment sequelae could be anticipated from the intensity and type of therapeutic modalities. Treatment-directed screening evaluations may improve quality of life in long-term survivors of pediatric GCT through timely identification of sequelae that can be prevented or ameliorated.

The elusive diploic veins: anthropological and anatomical perspective.

Diploic veins (Canales diploicae), which were identified in dogs by Dupuytren more than 200 years ago (Hecker [1845] Die anatomische Verhaltnisse und Krankheiten der Venae diploicae und Vasa emissaria. Erfahrungen und Abhandlungen im Gebiete der Chirurgie und Augenheilkunde. Erlangen), have remained inadequately understood and scantily referenced in the anatomical and anthropological literature. The tunnels formed by diploic veins are among the few known skeletal markers of soft tissue alteration. Protected by two bony laminae, diploic vein tunnels often resist postdepositional destruction and may provide a new way to assess living and extinct hominid populations. This basic research was carried out to enable future utilization of the diploic venous channels in anthropologic research. In the present study, diploic venous channels were observed radiographically in 108 human adults aged 19 years and above, 18 infants and children aged 1-18 years (Hamann-Todd Osteological Collection), eight fetuses aged 7-9 months (the Johns Hopkins Collection), and seven nonhuman primates (Hamann-Todd Osteological Collection). In addition, seven documented cases of parents and children were radiographed for genetic evaluation (Osteological Collection of The Hungarian Natural History Museum). Five distinct diploic distribution patterns were identified and described in this study. This was at variance with the impressions reported in dissection-based studies. Independence of diploic vein pattern from demographic (gender and age) and size factors and their tendency to be symmetrical make them amenable and reliable traits for skeletal population study. Diploic vein patterns appeared to be more complicated in humans than in nonhuman primates, raising the possibility of future phylogenetic applications.

Feasibility of implementing health promotion interventions to improve health-related quality of life.

Survivors of childhood cancer are a growing and vulnerable population. Cure rates for pediatric cancers now exceed 60% and, by the year 2000, an estimated 1 of every 1,000 young adults will be a cancer survivor. Because this population is at increased risk for late medical and neoplastic complications that impact adversely on health-related quality of life, it is important to investigate methods to promote risk reduction by motivating survivors to practice health-promoting behaviors. With this background, we initiated a prospective, randomized, controlled feasibility study in which survivors attending a long-term follow-up clinic were randomized to receive standard care or standard care plus an educational intervention. Our objectives were to determine if the intervention would improve the survivors' knowledge about their cancer treatment and risks of late effects and increase their practice of health-protective behaviors. Since July 1995, 272 of 318 families (86%) approached about the study agreed to participate. Of these, 266 are evaluable for assessment of baseline knowledge and health behaviors. Demographic features, baseline knowledge, health perceptions and health behaviors did not differ among randomized groups. Assessment of the intervention's efficacy at changing health behaviors of survivors randomized to the intervention group will be available when the 1-year follow-up evaluations are completed for the study cohort. Our preliminary experience with this pilot study supports the feasibility of educational intervention research in a specialty clinic dedicated to monitoring long-term childhood cancer survivors. Int. J. Cancer Suppl. 12:138-142, 1999.

Increased mortality after successful treatment for Hodgkin's disease.

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.

Clues to recognition of fungal origin of lytic skeletal lesions.

The present study addresses the specificity of lytic osseous impact for distinguishing among metastatic cancer, tuberculosis, and fungal disease. Osseous impact is used in this manuscript as a convention to describe the macroscopic appearance of defleshed bones affected by the disease. Osseous changes in the skeleton of a 47-year-old black male, diagnosed in life as having blastomycosis, were characterized and compared to lytic lesions observed in ten individuals with tuberculosis and six with metastatic cancer in the Terry and Hamman-Todd Collections. Apparent distinguishing characteristics are identified. Eroded areas, present as fronts of resorption or the result of space-occupying masses in blastomycosis, with protruding, short, blunt, 1 x 2 mm spicules of new bone, are surrounded by periosteal reaction. These differed from smooth zones of resorption and coalesced lesions, with a smoothed marginal zone and space-occupied appearance--bone-displacing mass--in tuberculosis and lytic (nonpermeative) lesions of metastatic cancer. Displacing is a convention (an artificial term) denoting bone resorption and reformation at the outer edge of the tumor mass, giving the impression that the surrounding bone had expanded beyond its original margins. Irregular trabeculae are occasionally preserved in the margins, but remodeling in the form of blunting of those trabeculae is not observed macroscopically in either tuberculosis or metastatic cancer. Two apparently specific lesion types are noted in blastomycosis. Periosteal reaction surrounding fronts of resorption appears specific, at least for nonarticular osseous lytic lesions, among the three entities studied. Remodeling of isolated internal trabeculae in the space-occupying mass lesions of blastomycosis also appears unique among the three disorders studied. Comparison with coccidioidomycosis suggests that extrapolation of blastomycosis findings to other fungal diseases is feasible; description of additional clinically diagnosed cases is awaited.

Treatment of children with peripheral primitive neuroectodermal tumor or extraosseous Ewing's tumor with Ewing's-directed therapy.

PURPOSE: We report the treatment and outcome of patients with peripheral primitive neuroectodermal tumor (PNET) and extraosseous Ewing's tumor (EOE) using Ewing's-directed therapy, including an ifosfamide and etoposide window. METHODS: Seventeen pediatric patients with peripheral PNET (n = 14) or EOE (n = 3) were enrolled between 1988 and 1992 on our institutional Ewing's protocol. Induction therapy comprised a 9-week "window" of ifosfamide and etoposide, followed by 9 weeks of therapy with cyclophosphamide and Adriamycin (Adria Laboratories, Columbus, OH). Response assessment after 17 weeks was followed by surgery and/or radiotherapy (doses based on tumor size and response to induction), repeat evaluation, and maintenance chemotherapy with alternating courses of vincristine/dactinomycin, ifosfamide/etoposide, and cyclophosphamide/Adriamycin for a total of 45 weeks. RESULTS: At diagnosis, 8 patients had large lesions (>8 cm) and 3 had pulmonary metastases (1 with large tumor). Surgical resection was performed at diagnosis for 9 patients and after induction therapy for 5. During window therapy, all of the 9 evaluable patients responded (8 partial, I objective), and no patient without measurable disease developed disease progression. Responses were maintained or improved during subsequent induction in six of the patients with residual disease. Fourteen patients received local radiotherapy. At 49 to 94 months after diagnosis, 12 patients are disease-free (1 in second remission), 4 have died, and 1 is alive with disease. The five-year overall and progression-free survival rates are 77 +/- 13% and 62 +/- 16%, respectively. CONCLUSION: The use of consistent Ewing's-directed combined-modality therapy for patients with soft tissue peripheral PNET/EOE results in survival similar to that of patients with osseous Ewing's tumor. The combination of ifosfamide and etoposide appears active and should be incorporated in future treatment protocols.

Breast masses in women treated for childhood cancer: incidence and screening guidelines.

BACKGROUND: The authors' aims were to define the frequency, characteristics, and methods of detection of breast masses in young women treated for childhood cancer and to develop screening guidelines for the growing population of long term survivors. METHODS: The authors reviewed medical records of all female patients treated for malignancy at a childhood cancer center over a 34-year period to identify those who developed a breast mass and to determine the cumulative incidence of breast cancer as a second primary cancer. RESULTS: A breast mass was identified in 66 patients who had been diagnosed with a malignancy at a median age of 13.8 years (range, 0.4-24.4 years). Masses were initially detected by breast self-detection in 32 and clinical examination in 28; the method of detection was unknown in 6 cases. Breast lesions were benign in 41 patients and malignant in 26; 1 patient had both a benign and a malignant lesion. Of the 26 malignant masses, 14 represented metastases of the primary malignancy and 12 were primary breast cancers as second primary cancers. The median interval to a primary breast cancer as a second primary cancer was 13.6 years (range, 9.2-24.4 years), and the median age at detection was 27.7 years (range, 12.5-43.1 years). The 25-year cumulative incidence of primary breast cancer as a second primary cancer in this cohort was 1.7% (95% CI, 0.4%-2.9%). This represented a 20-fold increase (95% CI, 10-36) over the expected incidence in age-matched and race-matched controls. CONCLUSIONS: Young women treated for childhood cancer have a significantly increased risk of breast cancer compared with age-matched controls. For this group of patients, the authors recommend patient education regarding this risk and the importance of properly conducted self-examination as the foundation of breast cancer screening. In addition, clinical and mammographic screening should be instituted at a younger age and performed more frequently than recommended for the general population of women.

A pilot study of vincristine, ifosfamide, and doxorubicin in the treatment of pediatric non-rhabdomyosarcoma soft tissue sarcomas.

BACKGROUND: Standard therapy for pediatric nonrhabdomyosarcoma soft tissue sarcomas (PNRSTS) consists of surgical resection with or without radiotherapy. The role of chemotherapy in the treatment of these tumors has not yet been defined. We investigated the efficacy and toxicity of an ifosfamide-based regimen in controlling disease in children with high-risk PNRSTS. PATIENTS AND METHODS: Between January 1992 and June 1994 at St. Jude Children's Research Hospital, we treated 11 children and young adults with PNRSTS who were at high risk for treatment failure by using a combined modality regimen that comprised aggressive surgery, radiotherapy, and chemotherapy including vincristine, ifosfamide, and doxorubicin (VID). Nine of these patients had grade 3 disease and one had grade 2 tumor; due to insufficient tissue, the disease grade of the remaining patient could not be established. Metastases were present at diagnosis in 2 children. RESULTS: Therapy was generally well tolerated, with minimal morbidity and no mortality. The most common toxicity was grade 4 neutropenia, which occurred in 51% of evaluable courses. Among 4 patients evaluable for response to chemotherapy alone, 1 child attained a partial response and 3 had stable disease. One child had a response to chemotherapy and concurrent irradiation. At a median follow-up of 30 months, 10 of 11 patients are alive; 8 of 11 patients are alive without evidence of disease. CONCLUSION: Aggressive multimodality therapy for PNRSTS is well tolerated, despite frequent and profound neutropenia. Although adjuvant chemotherapy for this group of cancers remains unproved, the rate of tumor control achieved in this pilot study encourages further investigation in a multi-institutional setting.

Recognition of sickle cell anemia in skeletal remains of children.

The present study discusses in detail the osteological changes associated with sickle cell anemia in children and their importance in differential diagnosis. Posterior calcaneal and specific articular surface disruptive metacarpal lesions are diagnostic for sickle cell anemia. Calvarial thickening, tibial and femoral cortical bone thickening, and bowing are of more limited utility in differential diagnosis. Granular osteoporosis, pelvic demineralization and rib broadening are nonspecific. Localized calvarial "ballooning," previously not described, may have diagnostic significance. Bone marrow hyperplastic response (porotic hyperostosis) in sickle cell anemia produces minimal radiologic changes contrasted with that observed in thalassemia and blood loss/hemolytic phenomenon. Two other issues, the osteological criteria for discriminating among the anemias and the purported relationship between porotic hyperostosis and iron deficiency anemia, are also discussed. There is sufficient information to properly diagnose the four major groups of anemias, and further, to establish that iron deficiency is only indirectly associated with porotic hyperostosis. The hyperproliferative bone marrow response (manifest as porotic hyperostosis) to blood loss or hemolysis exhausts iron stores, resulting in secondary iron deficiency.

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.

Outcome of treatment for pediatric sarcoma of the foot: a retrospective review over a 20-year period.

Soft tissue sarcomas (STS) arising in the foot are rare in children. From 1975 to 1994, 18 children (median age, 13.5 years) were treated at St Jude Children's Research Hospital for STS of the foot. Five children had rhabdomyosarcoma (RMS), with alveolar histology in four cases. All of these patients presented with metastatic disease, which proved fatal within 9 to 24 months despite combined modality treatment with chemotherapy, radiation, and surgery. Thirteen patients had nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The most common histological variant was synovial sarcoma (7 patients). Of the 10 who presented with localized disease, seven survived 1 to 12 years (median, 7 years). Surgical treatment for these consisted of local excision (n = 2), wide local excision (n = 3), below knee amputation (n = 1 ), ray amputation (n = 1). Three received supplemental radiation, and one was also treated with chemotherapy. Local or distant recurrence proved fatal in the three other children who had localized disease. Three children who presented with metastatic NRSTS died 8 to 14 months after diagnosis. All surviving patients are without significant functional disability. In our experience, pediatric RMS of the foot has a poor outcome, attributable to both alveolar histology and presence of metastatic disease at diagnosis. In contrast, NRSTS of the foot is more often localized, and limited surgery with adjuvant radiation in the absence of clear margins should be the treatment of choice.

Dental abnormalities in children treated for acute lymphoblastic leukemia.

The purpose of this study was to define the therapy-associated dental abnormalities in survivors of acute lymphoblastic leukemia (ALL). We reviewed the clinical records and panoramic radiographs of 423 survivors of ALL who were treated on one of four consecutive protocols (1975-1991). Dental abnormalities included root stunting, microdontia, hypodontia, taurodontia (enlarged pulp chambers), and over-retention of primary teeth. The frequency of these factors was determined in relation to age at initiation of treatment (< or = 8 years vs > 8 years), addition of cranial irradiation, and chemotherapeutic protocol. A total of 423 patients met the study criteria. The abnormalities comprised root stunting in 24.4% (n = 103), microdontia in 18.9% (n = 80), hypodontia in 8.5% (n = 36), taurodontia in 5.9% (n = 25), and over-retention of primary dentition in 4.0% (n = 17). Patients who were < or = 8 years old at diagnosis or who received cranial irradiation therapy developed more dental abnormalities than did those > 8 years and those who did not receive cranial irradiation (42 vs 32%). Survivors of childhood ALL often have dental abnormalities that may affect their quality of life. Dental evaluation at diagnosis and frequent follow-up may help to ensure appropriate preventive measures and minimize dental and periodontal disease.

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).

Ultrasonography for thyroid screening after head and neck irradiation in childhood cancer survivors.

We prospectively used ultrasonography to detect thyroid abnormalities in 96 long-term survivors of childhood cancer, who received head and neck radiation therapy at a median age of 8.9 years. The median time interval since irradiation was 10.8 years (range 5.6-22.8 years). Most survivors of leukemia received 24 Gy cranial irradiation for central nervous system prophylaxis; patients with solid tumors received between 20 and 66 Gy (median 37.5 Gy). The total evaluation included clinical history, physical examination, thyroid function tests, and thyroid ultrasonography; radionuclide scans were performed in patients whose abnormalities persisted on subsequent ultrasound exams. Clinical history and physical examination revealed thyroid abnormalities in 14 patients (15%), but ultrasound detected abnormalities in 42 patients (44%). These findings included inhomogeneity (n = 29), cysts (n = 15), and nodules (n = 22) and occurred in nearly half of patients treated with 15 Gy or more directly to the thyroid gland. Radionuclide scans confirmed the presence of thyroid nodules in 13 of 15 patients with ultrasonographic evidence of nodules. Six patients had thyroid neoplasia, including one case of papillary carcinoma. All patients with neoplasia had nodules demonstrated on ultrasonography. Our experience suggests that in childhood cancer survivors, ultrasonography is a sensitive, affordable, and noninvasive means of detecting subtle parenchymal abnormalities. We recommend thyroid ultrasonography for childhood cancer survivors who received head and neck irradiation. A baseline study should be obtained within 1 year of completion of therapy. The frequency of subsequent examinations should be based on the radiation dose and the patient's age at the time of irradiation.

Epithelioid sarcoma in children.

Literature regarding the natural history and prognosis of epithelioid sarcoma in the pediatric population is sparse. During the past 11 years, eight patients with epithelioid sarcoma were treated at St Jude Children's Research Hospital. Of the eight children, six of whom were male, seven presented with localized disease and one with metastatic disease. The primary tumor was located in the upper extremity in four patients; the other sites were the scalp, external ear, back, and mediastinum. The mean duration of symptoms before diagnosis was 8.3 months (range, 1 to 12 months). Surgical treatment comprising amputation or wide local excision was performed in six patients, three of whom had additional lymph node dissection. Three patients received multiagent chemotherapy, and four patients were treated with supplementary radiation. Two patients died of progressive local and distant disease within 9 months of diagnosis. The other six patients are alive and have no evidence of disease 12 months to 10 years 6 months after the completion of treatment.

Local control in synchronous bilateral Wilms tumor.

PURPOSE: To evaluate the role of radiation therapy (RT), chemotherapy (CT), and surgery in the local control of synchronous bilateral Wilms Tumor (WT). METHODS AND MATERIALS: Between 1962 to 1993, 45 children were treated for bilateral WT; 38 patients with synchronous tumors were reviewed. Initial surgery depended on the era of treatment and included unilateral nephrectomy (N)/partial nephrectomy (PN) and contralateral PN in 6, unilateral N/PN alone in 7, and biopsy only in 25. Chemotherapy (CT) consisted of vincristine, actinomycin-D, and adriamycin in 32 and vincristine/ actinomycin-D in 6. Radiation therapy (RT) was given to 32 patients. Treatment included both kidneys in 20, unilateral kidney plus contralateral renal bed in 9, unilateral kidney in 2, and unilateral renal bed in 1. Follow-up was 16 months to 25 years (median: 6.3 years). RESULTS: Local control (LC) has been maintained in 66 out of 76 sites (87%). For Stage I-II disease with initial N/PN, LC was 10 out of 12 with RT and 11 out of 11 without RT; for Stage III with initial N/PN, LC was 8 out of 9 with RT and 1 out of 1 without RT. Initial CT and RT was followed by delayed N/PN for 20 sites; LC was 15 out of 17 in post induction Stage I-II and 1 out of 3 in postinduction Stage III. In 23 sites undergoing biopsy and chemotherapy, LC was 19 out of 20 with RT and 1 out of 3 without RT. Seven of 23 sites had a complete response (CR) after induction CT, and LC was maintained in four out of four with RT and one out of three without RT. Univariate Cox Regression analysis demonstrated that sites receiving two drugs had a statistically significant increase in loco-regional relapse when compared to sites receiving three drugs (p = 0.004). Major morbidities related to multimodality therapy have included renal failure in one patient and small bowel obstruction requiring lysis of adhesions in two patients. CONCLUSIONS: Local control does not seem to be compromised by renal conservation therapy. Local control is excellent in sites treated with radiation therapy in combination with three drug chemotherapy.