Interstitial brachytherapy for childhood soft tissue sarcoma

BACKGROUND: To evaluate the efficacy of interstitial brachytherapy (BRT) in children undergoing combined modality treatment for soft tissue sarcomas (STS). PROCEDURE: From September 1984 to December 2003, 50 children (median age 13 years, range 1 to 18) with STS who received BRT as part of loco-regional treatment were included. There were 30 males and 20 females, the majority (68%) had primary lesions, synovial sarcoma (32%) was the most common histological type, and 26% had high-grade lesions. Treatment included wide local excision and BRT with or without external beam radiotherapy (EBRT). Thirty children (60%) received BRT alone. RESULTS: After a median follow-up of 51 months, the local control (LC), disease-free survival, and overall survival were 82%, 68%, and 71%, respectively. LC was superior in patients with tumor size 5 cm (96% vs. 67%, P = 0.04), symptom duration <2 months versus >2 months (100% vs. 73%, P = 0.05), and Grade I versus Grade II versus Grade III tumors (100% vs. 93% vs. 57%, P = 0.03). Children receiving a combination of BRT and EBRT had comparable LC to those receiving BRT alone (78% vs. 84%, P = 0.89). There was no significant difference in LC for patients receiving LDR versus HDR BRT (77% vs. 92%, P = 0.32, for BRT alone; and 67% vs. 100%, P = 0.17, for BRT + EBRT). CONCLUSION: Interstitial BRT with or without EBRT appears to result in satisfactory outcome in children with STS. Radical BRT alone, when used judiciously in select groups of children, results in excellent local control and functional outcome with reduced treatment-related morbidity.     

Intraoperative electron beam treatment for pediatric malignancies: The Ohio State University experience

PURPOSE: To report the result of intraoperative electron beam radiation therapy (IOERT) in patients with extensive pediatric tumors. METHOD: From October 1989 through June 2000, 13 children were treated with chemotherapy, maximal surgery, and 10-15 Gy IOERT at a total of 18 sites. IOERT was used for palliative purposes in 5 children with metastatic disease and in 3 others who were previously treated with external beam radiation (EBRT). The remaining five patients received definitive IOERT. Postoperative EBRT of 35.4-45 Gy was given in 5 patients. RESULTS: After a median follow-up of 42 months (range = 18-63 months), 4 patients were alive and without evidence of disease. Overall and 3 year actuarial survival rates were 31% (4/13) and 26%, respectively. Local control was achieved at 13/18 sites (72%). Poor prognostic factors included metastatic disease, recurrent disease, and the absence of adjuvant EBRT. Two children with Wilms tumors had 100% local control, disease-free survival, and overall survival without the addition of EBRT. CONCLUSION: A boost dose of IOERT allows for reduction in the dose of EBRT, thereby limiting growth-related morbidity without compromising local control or disease-free survival. Except for Wilms tumors, which achieved 100% local control and disease-free survival, adjuvant EBRT is necessary for successful local control and survival in children with soft tissue sarcomas. Based on this study and others, intraoperative irradiation should be considered for inclusion in prospective, multi-institutional trials designed to treat localized malignancies in young children.     

Long-term morbidity in children treated with fractionated high-dose-rate brachytherapy for soft tissue sarcomas

BACKGROUND: The purpose of this study was to determine the long-term local control, disease-free survival, and morbidity of fractionated high-dose-rate brachytherapy (F-HDR) in infants and children with soft tissue sarcomas. PATIENTS AND METHODS: Fifteen children (13 girls and 2 boys, ages 5-101 months) with soft tissue sarcomas were treated with chemotherapy, organ-preserving surgery, and F-HDR (36 Gy in 12 fractions) to post-chemotherapy volumes. External beam radiotherapy was not part of the primary treatment, although four patients (27%) subsequently received salvage external beam radiotherapy after treatment failure. Chemotherapy was administered to all patients based on their tumor histology and stage. RESULTS: After a median follow-up of 10 years (range 32-154 months), 12 patients (80%) were alive without evidence of disease. Ten-year overall survival and local control rates were both 80% (12/15 children). The overall survival was better (91%) for children with microscopic residual versus gross residual disease (75%). With longer follow-up, grade 3 to 4 brachytherapy-related late morbidities increased from 8% (1/12) to 20% (3/15) and included trismus/osteonecrosis, vaginal stenosis, and periurethral fibrosis. There were two late complications associated with puberty that occurred 8 to 10 years after the initial treatments. Acute toxicity occurred in five patients (38%) and consisted primarily of grade 1 to 3 skin and mucosal reactions. CONCLUSIONS: As the sole radiation modality, F-HDR achieved excellent local control and disease-free survival in properly selected children with soft tissue sarcomas while preserving normal bone and organ development. A significant percentage of patients experience adverse late sequelae as a result of this treatment.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents.

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisciplinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6-20 MeV electron beams. The median follow-up time for the entire group is 25 months (2-65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.     

Brachytherapy for solid tumors in children

The standard treatment after surgery and chemotherapy in pediatric solid tumors is external beam to the tumor with a generous (5 cm) margin for local control. This treatment is given over a five to six-week period, requires use of repeated deep sedation, and leads to unacceptable morbidity (especially organ and bone-growth retardation) in infants and younger children. Limited volume irradiation by brachytherapy over a few days may be sufficient therapy for children treated with aggressive chemotherapy. Brachytherapy allows high doses of radiation to be limited accurately to the tumor bed, spares the surrounding normal tissues, and thus minimizes late sequelae. Manually afterloaded removable iridium-192, iodine-125, and cesium-137 have been used with good results. The major disadvantages of LDR brachytherapy are: the necessary sedation and immobilization of younger children to prevent accidental removal of the implants during the entire period, radiation exposure to the medical personnel and the parents, and the psychological effect of separating parents from their child. Using a low energy radionuclide such as iodine-125, or remote afterloading technology with LDR and PDR reduces radiation exposure hazards, but prolonged sedation and immobilization are still required. HDR brachytherapy not only eliminates the radiation exposure hazards but, in addition, eliminates the other disadvantages of brachytherapy thereby extending treatment to the infants and younger children. The long term effects of brachytherapy need further study.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisci plinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6–20 MeV electron beams. The median follow-up time for the entire group is 25 months (2–65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.     

Combined radiation and chemotherapy for advanced undifferentiated nasopharyngeal carcinoma in children

Five children, 11–16 years of age at diagnosis, with advanced (stage IV) undifferentiated nasopharyngeal carcinoma, are reviewed. All had radiotherapy and chemotherapy, four at first treatment, are disease free in 8 months, 6, 10, and 13 years from diagnosis. One patient who had radiotherapy only as primary treatment and chemotherapy for metastases, died 15 months from diagnosis. One patient who received 60 Gy and chemotherapy according to the BACON protocol had severe early toxicity and severe late sequelae of treatment. Three patients who received chemotherapy according to a modified UICC-2 protocol for nasopharyngeal carcinoma and 50 to 54 Gy to the primary site had only mild early toxicity and mild late effects of treatment. With lower radiation doses, adjusted to the effect of preradiation chemotherapy, complete tumor control was achieved and acute and long-term morbidity reduced. Med. Pediatr. Oncol. 28:366–369, 1997. © 1997 Wiley-Liss, Inc.     

Endocurietherapy in pediatric oncology

Endocurietherapy (brachytherapy) is the placing of radioactive sources directly into or near a solid tumor. This technique delivers a concentrated dose of radiation to a restricted volume while minimizing radiation effects on normal tissue. We have treated 11 patients (nine sarcomas, one carcinoma, and one Wilms') with endocurietherapy procedures as part of their multimodality treatment program. Six were treated as part of the primary management, and the other five were treated for recurrent or metastatic disease. Temporary afterloaded implants using ribbons embedded with radioactive iridium192 (Ir192) seeds delivered typical tumor doses of 4,000 cGy. Six patients, including four primary cases and two recurrent cases, are currently classified as no evidence of disease (NED) without further local regional treatment (follow-up of 11-62 months; median, 38 months), and one patient treated for metastasis also remains locally controlled. Two patients are classified as alive with disease (AWD), two died of disease (DOD), and one is now NED after surgical salvage. Special considerations were given to gonadal shielding, radioprotection techniques, and psychosocial issues in this pediatric population.     

Clear cell sarcoma of soft tissues in children and young adults: the St. Jude Children's Research Hospital experience

Clear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.     

Surgical management of pelvic sarcomas in children

Pelvic sarcomas are uncommon in childhood. Survival rates of children with pelvic sarcomas have shown significant improvements over the past few decades. Correspondingly, there has been an increase in limb-sparing surgical procedures being performed in these children. This could be attributed in part to the newer generation imaging techniques, wider armamentarium of surgical techniques of reconstruction, and limb-salvage and advances in neo-adjuvant chemotherapy and radiotherapy. Reconstruction after resection of pelvic sarcomas while preserving function of the hip and limb can be extremely challenging especially in children where there are issues of growth potential and limb-length discrepancies. This article focuses on the presentation and epidemiology of different types of pelvic sarcomas in children, the current state-of-art of imaging and surgical management of children with pelvic sarcomas.     

Intra-operative radiation therapy in pediatric neuroblastoma

External beam irradiation (EBRT) has been shown to improve response rates and event-free survival in children with neuroblastoma and regional lymph node metastases. Irradiation during surgical exposure (intra-operative radiotherapy, IORT) with displacement of adjacent radiosensitive organs out of the treatment field allows for more precise delineation of the target volume and significantly reduces the amount of normal tissue exposed to irradiation. We have incorporated IORT into the treatment regimen of 24 children with neuroblastoma between the years 1983–1991. IORT was directed to any residual tumor or the tumor bed; the median dose of radiation was 1,000 cGY, equivalent to 3,000 cGY of conventional EBRT. There were 11 males and 13 females. Two patients had stage II, 12 patients had stage III, and 10 patients had stage IV disease. Ten children received IORT for suspected recurrent or persistent neuroblastoma. Twelve patients were disease-free survivors following IORT with a median follow-up of 54 months. For those patients with stage III disease, seven children were disease-free survivors, while only three of 10 patients with stage IV disease survived (median follow-up 30 months). Disease-free Survival (DFS) correlated with the achievement of local tumor control in children with both stage III and IV neuroblastoma. There was limited morbidity and no episodes of obstructive uropathy were encountered. We conclude that IORT appears to be well tolerated and may have therapeutic benefit for a select group of patients with neuroblastoma. IORT merits future exploration by prospective study. Med. Pediatr. Oncol. 28:424–428, 1997. © 1997 Wiley-Liss, Inc.     

VM-26 and dimethyl triazeno imidazole carboxamide in Ewing's sarcoma

Twenty-seven patients with biopsy proven Ewing's sarcoma were randomised to receive one of two adjuvant chemotherapy regimens for two years. Group A were given monthly courses of vincristine, adriamycin and dimethyl triazeno imidazole carboxamide (DIC); Group B received monthly courses of VM-26, adriamycin and DIC. Chemotherapy was commenced after biopsy confirmation of disease. The primary tumour was treated with irradiation to 3,000-5,000 rad and by resection in three patients. With a median follow-up of 26 months, 52% of patients are disease free. Ten patients died, seven from recurrent disease and three from complications of treatment. There was a significant difference in disease free survival rate of patients with long bone lesions (11/12) compared with patients with flat bone lesions (6/15). The disease free survival rate of Groups A and B was similar. Our results suggest that in combination chemotherapy for Ewing's sarcoma, vincristine and VM-26 have similar anti-tumour activity.     

VM-26 and dimethyl triazeno imidazole carboxamide in Ewing's sarcoma

ABSTRACT. Twenty-seven patients with biopsy proven Ewing's sarcoma were randomised to receive one of two adjuvant chemotherapy regimens for two years. Group A were given monthly courses of vincristine, adriamycin and dimethyl triazeno imidazole carboxamide (DIC); Group B received monthly courses of VM-26, adriamcyin and DIC. Chemotherapy was commenced after biopsy confirmation of disease. The primary tumour was treatedd with irradiation to 3,000–5,000 rad and by resection in three patients. With a median follow-up of 26 months, 52% of patients are disease free. Ten patients died, seven from recurrent disease and three from complications of treatment. There was a significant difference in disease free survival rate of patients with long bone lesions (11/12) compared with patients with flat bone lesions (6/15). The disease free survival rate of Groups A and B was similar. Our results suggest that in combination chemotherapy for Ewing's sarcoma, vincristine and VM-26 have similar anti-tumour activity.     

Favorable response to soft tissue sarcoma therapy in an adolescent with embryonal renal sarcoma

Embryonal renal sarcomas were first identified in 1995 among banked tumor samples originally classified as adult Wilms tumor. Few long-term remissions were observed when these rare tumors were treated with chemotherapy usually used for childhood Wilms. Data were collected from the medical record of an adolescent female with embryonal renal sarcoma and treated with sarcoma-directed chemotherapy and radiation. At 66 months following diagnosis, the patient has no evidence of tumor but has experienced severe renal dysfunction and ovarian failure. We believe there is a subset of patients with disseminated embryonal renal sarcoma that respond to intense sarcoma-directed therapy.     

儿童粒细胞肉瘤4例报告并文献复习

目的提高对粒细胞肉瘤(GS)的起病方式、临床病理特征、诊断及治疗的认识。方法对4例儿童GS进行起病方式、免疫病理、诊断及治疗的分析并复习相关文献。结果非白血病性GS3例,白血病性GS1例。4例免疫病理检测中3例MPO均为阳性;2例CD99阳性,1例CD99(+/-);2例CD68(Kp-1)阳性;1例CD43阳性。而作为淋巴瘤标记的CD3、CD20、TDT均为阴性。结论GS诊断主要依据病理活检及免疫组化检测,其治疗主要是按照AML的方案给予系统化疗,为达到长期无病生存,在系统化疗取得缓解后,可及早进行造血干细胞移植。     

High-dose melphalan therapy for the treatment of children with refractory neuroblastoma and Ewing's sarcoma

Neuroblastoma and Ewing's sarcoma are examples of pediatric cancers in which disseminated disease is often present at diagnosis or develops later in spite of combination therapy. The demonstration that marrow-ablative doses of chemotherapy can increase tumor cell kill, and that autologous bone marrow can be cryopreserved and reinfused into the patient to reverse such marrow ablation, has stimulated interest in this approach to refractory childhood cancers. We present results of treating eighteen patients with recurrent neuroblastoma and Ewing's sarcoma resistant to conventional therapy. We used supralethal doses of melphalan, supported by reinfusion of previously cryopreserved autologous bone marrow. Seven of 10 neuroblastoma and six of eight Ewing's sarcoma patients had complete or partial responses, lasting for a median of 6 months (neuroblastoma) and 3 months (Ewing's sarcoma). Prolonged hospitalization, pancytopenia complicated by sepsis, and reversible gastrointestinal toxicity were the major side effects. These results suggest this approach should be tested in therapeutic trials at an earlier disease stage in children who have cancers with a predictably bad prognosis.     

Ocular preservation after 36 Gy external beam radiation therapy for retinoblastoma

PURPOSE: The purpose of this study was to document the ocular preservation rate after 36 Gy external beam radiation therapy (EBRT) for retinoblastoma. PATIENTS AND METHODS: Forty-nine eyes of 38 patients were treated with a median dose of 36 Gy EBRT. The patient population included 7 unilateral and 31 bilateral presentations, with a median age at diagnosis of 4 months. Eyes enucleated at the time of diagnosis or treated with other measures were not included in the analysis of ocular preservation. The median age at EBRT was 8 months. Patients were monitored for progression of disease after EBRT and second malignant neoplasms. RESULTS: The median follow-up was 88.6 months, with an estimated ocular preservation rate of 82.0% +/- 5% at 10 years. There was a difference in the ocular preservation rates for patients with advanced disease (Reese-Ellsworth group III-V) compared with early disease. Metastatic disease developed in two patients, and a second malignant neoplasm developed in three. Patients treated with en face electrons experienced a lower 5-year estimate of ocular preservation than those treated with photons, although patients treated with electrons were more likely to have advanced disease. CONCLUSIONS: The use of low-dose EBRT (36 Gy) results in ocular preservation rates that are comparable to those of high-dose EBRT. The use of electrons requires careful treatment planning and computerized dosimetry.     

Leiomyosarcomas in children: clinical and pathologic characteristics

Leiomyosarcomas (LMS) are extremely rare in children, accounting for only 2% of their soft-tissue sarcomas [11]. We report our experience with nine children treated for LMS between 1962 and 1990. Their ages at diagnosis ranged from 1 day to 17 years (median 5 years); six were female and eight were Caucasian. Five tumors were stromal sarcomas originating in the gut (ileum 2, stomach 1, jejunum, sigmoid 1). Three were intra-abdominal tumors that originated in the retroperitoneum (2) and abdominal wall (1). In one patient the tumor appeared in the subcutis of the thigh. Operations were uniformly performed, resulting in complete resection of the tumor in six of nine cases. Five patients received adjuvant chemotherapy and one received radiation therapy only. Five patients were alive 6–38 months (median 16 months) after diagnosis. The remaining four died of their disease 4–27 months after diagnosis, three of locally recurrent disease and one of hepatic metastasis. Four of the six patients with complete resection were alive 6–27 months after diagnosis. Both patients with low-grade (grade I) sarcomas had complete resections and were alive 33–38 months after diagnosis. Clinical outcome correlated roughly with the mitotic rate of the tumors, as all three patients with mitotic count >5/10 high power fields (HPF) died between 4 and 14 months after diagnosis. Immunohistochemical stains using the avidin-biotin-complex procedure on formalin-fixed tissue were performed for six tumors. Only muscle-specific actin (MSA) was uniformly positive (6/6). The other significant marker was desmin, which was positive in three tumors. Favorable outcome of LMS in children correlates best with low mitotic counts (<5/10 HPF), low tumor grade, and complete surgical excision. Immunohistochemical analysis suggests that these tumors are of myogenic origin.Supported by childhood Solid Tumor Program Project Grant No. CA-23 099 and Cancer Center Support (CORE) Grant No. CA-21 765 from the National Cancer Institute, Bethesda, Maryland and the American Lebanese Syrian Associated Charities (ALSAC).     

Generation of patient‐derived tumor xenografts from percutaneous tumor biopsies in children with bone sarcomas

One of the limitations of performing percutaneous biopsies in patients with bone sarcomas is the small amount of tumor that can be obtained for research purposes. Here, we describe our experience developing patient‐derived tumor xenografts (PDXs) using percutaneous tumor biopsies in children with bone sarcomas. We generated 14 bone sarcoma PDXs from percutaneous tumor biopsies. We also developed eight bone sarcoma PDXs from surgical resection of primary bone tumors and pulmonary metastases. A multidisciplinary team approach was critical to establish an accurate diagnosis and to provide adequate tumor samples for PDX generation.     

Positron emission tomography/computed tomography with 18fluoro-deoxyglucose in the detection of local recurrence and distant metastases of pediatric sarcoma

BACKGROUND: Combined positron emission tomography with (18)fluoro-deoxyglucose and computed tomography (FDG-PET/CT) has been used in the diagnosis and staging of various malignancies, but their use in the management of pediatric sarcomas is less well defined. The potential role of FDG-PET/CT in the diagnosis of local recurrence and distant metastases of pediatric sarcomas was investigated. PROCEDURE: Nineteen children (aged 2-21) with sarcoma (9 Ewing sarcoma, 3 osteogenic sarcoma, 7 rhabdomyosarcoma) were evaluated between January 2000 and December 2005 by FDG-PET/CT for suspected local relapse or distant metastases. The results of 21 FDG-PET studies, 16 CT scans, 9 magnetic resonance imaging (MRI) studies, and 7 bone scans (BSs) were compared with surgical pathology or clinical follow-up for at least 3 months. RESULTS: FDG-PET detected local relapse in all seven patients and distant metastases in 10/13 (77%). FDG-PET/CT and CT/MRI/BS results were discordant in eight patients. FDG-PET/CT was the only modality that detected distant metastases in two patients. PET/CT was true negative and excluded disease in three patients with abnormal CT/BSs and was false negative in three patients with distant metastases. CONCLUSION: FDG-PET/CT may be useful and complementary to other imaging modalities for the detection of recurrent pediatric sarcomas, especially at the primary site. Its potential advantages and limitations compared with conventional imaging modalities need to be further investigated in larger homogenous patient groups.