High long-term local control with sacrectomy for primary high-grade bone sarcoma in children

Background  

Sacrectomy may offer curative potential for primary sarcomas of the sacrum. However, it is unclear whether and to what extent sacrectomies achieve local control.     

Perioperative chemotherapy for primary sarcoma of bone

Preoperative chemotherapy for primary osteosarcoma has usually been accompanied by a prolonged delay between withdrawal before operation and resumption after. This is because animal studies showed impaired wound healing associated with perioperative chemotherapy. Clinical studies, however, have not shown this to be the case. The authors describe their experience in eight patients who had osteosarcoma and Ewing's sarcoma of the extremities and received one to three cycles of chemotherapy preoperatively. Chemotherapy consisted of Adriamycin, cis-platinum and vincristine. Definitive surgery on the primary tumour was done 1 to 4 days after the last dose. Amputation was performed on seven patients and tumour resection for limb salvage on one. No wound healing or infectious complications were encountered. The ensuing course of chemotherapy was not delayed by the surgical procedure. The authors conclude that it is feasible to combine neoadjuvant chemotherapy and early surgery in the management of high-grade primary bone sarcoma.     

Neoadjuvant chemotherapy for high-grade advanced gastric cancer

Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m², mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 14) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered.

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Resumen Cincuenta y cinco casos de cáncer gástrico avanzado, en los cuales se había confirmado el Estado IV mediante imágenes diagnósticas preoperatorias, recibieron quimioterapia PMVE con el uso combinado de cisplatino (CDDP) 75 mg/m², MMC 10 mg/cuerpo, Ectoposide 150 mg/cuerpo y VHF 400 mg/día. El CDDP y el MMC fueron administrados por vía intravenosa en el primer día, seguidos de Ectoposide 50 mg/día en los días 3, 4 y 5. Todos los pacientes exhibían lesiones medibles, las cuales fueron valoradas por escanografía computadorizada antes y después del tratamiento. Los pacientes fueron ubicados al azar en dos grupos; 29 quedaron en el grupo de la quimioterapia neoadyuvante (QNA) en el cual la quimioterapia PMVE fue practicada preoperatoriamente, y los 26 pacientes restantes fueron sometidos primero a operación y luego a quimioterapia PMVE, constituyendose en el grupo de control. Los antecedentes médicos no eran significativamente diferentes en los dos grupos. La respuesta fue mayor en el grupo de QNA en comparación con el grupo control (62% vs 35%). La tasa de resecabilidad fue de 79% y 88% en el grupo QNA y en el grupo de control, respectivamente. Sin embargo, la rata de casos potencialmente curables fue más alta en el grupo de QNA, en comparación con el grupo control (38% vs 15%). En los casos no resecados, sin embargo, la tasa de sobrevida fue significativamente superior en el grupo de QNA en comparación con el grupo control. Tales resulados pueden significar que en pacientes con cáncer gástrico de alto grado y en estado avanzado se debe considerar primero la quimioterapia como paso inicial (quimioterapia neodyuvante), y luego la cirugía.

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Résumé Cinquante-cinq cas de cancer gastrique avancé, à potentiel très malin (stade IV à l'imagerie préopératoire), ont été traités par une chimiothérapie PMUE comprenant une combinaison de CDDP, 75 mg/m², MMC, 10 mg/Kg poids corporel, d'etopocide, 150 mg/Kg poids corporel et d'UFT, 400 mg/jour. Le CDDP et le MMC ont été donnés par voie intraveineuse à Jl, suivis d'etoposide, 50 mg/jour aux jours 3, 4 et 5. Tous les patients avaient des lésions qui ont pu être évaluées par la tomodensitométrie avant et après le traitement. Ces patients ont été randomisés en deux groupes: 29 ont eu une chimiothérapie néoadjuvante (CNA) par le PMUE en préopératoire, alors que les 26 autres ont d'abord été opérés, et ensuite ont reçu une chimiothérapie PMUE (groupe contrôle). Les caractéristiques des deux groupes ne différaient pas de façon significative. Le taux de réponse était plus haut dans le groupe CNA par rapport au groupe contrôle (62% contre 35%). Le taux de résecabilité était respectivement, de 79 et 88% dans les deux groupes. Le taux de cas potentiellement curables, cependant, était plus élevé dans le groupe CNA par rapport au groupe contrôle (38% contre 15%). Dans les cas de cancer gastrique non réséqués, le pronostic était extrêmement mauvais, quel que soit le groupe. Dans les cancers réséqués, la survie était significativement plus élevée dans le groupe CNA comparé au groupe contrôle. Ces résultats indiquent que chez les patients ayant un cancer gastrique avancé à potentiel très malin, une chimiothérapie néoadjuvante (d'emblée), suivie de chirurgie, peut être le meilleur choix thérapeutique.

     

Osteoporosis in children and young adults: a late effect after chemotherapy for bone sarcoma

Background  

Premature bone loss after childhood chemotherapy may be underestimated in patients with bone sarcoma. Methotrexate (MTX), a standard agent in osteosarcoma protocols, reportedly reduces bone mineral density (BMD). The literature, however, has reported cases of BMD reduction in patients with Ewing's sarcoma treated without MTX. Thus, it is unclear whether osteoporosis after chemotherapy relates to MTX or to other factors.     

Oral undifferentiated high-grade pleomorphic sarcoma: report of a case.

The current World Health Organization classification considers the existence of an undifferentiated unclassifiable category of pleomorphic sarcomas, defined as a group of pleomorphic high-grade sarcomas. Undifferentiated high-grade pleomorphic sarcoma represents about 5% of all soft tissue sarcomas in adults and occurs more commonly in the extremities. In the oral cavity, undifferentiated pleomorphic sarcoma is extremely rare. We report a case of undifferentiated high-grade pleomorphic sarcoma located in the floor of the mouth in a man 56 years old. Microscopically, spindle-shaped cells with accented pleomorphism arranged in a storiform pattern, several bizarre giant cells, and frequent atypical mitoses were observed. The tumor cells were positive only for vimentin, with focal positivity for CD68. The patient was treated by surgery and postoperative radiation therapy, and after 25 months, no recurrence was observed.     

Multidisciplinary treatment for childhood sarcoma.

Surgical extirpation of the primary tumor has traditionally been utilized as initial treatment for sarcomas in children. The present report, however, demonstrates that sarcomas are optimally treated by means of a coordianted multidisciplinary approach. The latter offers the potential for achieving improved survival and preservation of organs and limbs, particularly for structures of the head and neck, for extremities, and in the genitourinary system.     

Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

Background  

Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy.     

Radiation treatment of Ewing's sarcoma and osteogenic sarcoma.

At the Princess Margaret Hospital, Toronto, during the period 1960 to 1975, radiation therapy was given to 59 patients with Ewing's sarcoma without overt metastases. Over this period treatment was modified to include, as well as irradiation to the primary tumour, total body irradiation (TBI) and chemotherapy according to various regiments. The 5-year survival rate of 38% in 26% patients who received TBI suggests that this may be of value. In patients with osteogenic sarcoma preoperative irradiation was not found to be of value. Recently the resection of pulmonary metastases combined with chemotherapy has increased the survival rate. When the primary site makes resection impracticable, the response to irradiation and chemotherapy is encouraging. Three cases so treated are described.     

骨原发尤文肉瘤预后相关因素的分析

目的 明确骨原发尤文肉瘤患者的治疗结果,分析影响预后相关因素.方法 回顾性分析1998年7月至2007年7月就诊的78例骨原发尤文肉瘤患者的临床资料.通过随访了解肿瘤学预后,明确5年总体生存率及局部复发率.通过回顾病例,分析年龄、性别、肿瘤部位、肿瘤大小、初次诊断时有无转移、乳酸脱氢酶、碱性磷酸酶水平、治疗方式、外科边界等因素对总体生存率的影响.利用Kaplan-Meier生存分析确定对生存有影响的单个因素,并通过Cox回归分析明确影响预后的独立危险因素.结果 53例患者获得随访,中位随访时间37.6个月(8.0～101.0个月).患者5年总体生存率为33.7%,局部复发率20.8%,中位复发时间20个月.单因素分析结果显示:年龄＜20岁、初诊时元转移、病变位于四肢、肿瘤直径＜10 cm、取得广泛外科边界的患者预后较好(P＜0.05);多因素分析显示初诊时转移情况、肿瘤部位、肿瘤直径是影响预后的独立危险因素.结论 初诊时有无转移、肿瘤的部位和大小是影响骨尤文肉瘤预后的独立危险因素.     

Preoperative radiotherapy and chemotherapy in hypervascular, high-grade supratentorial astrocytomas.

From a group of ten patients with hypervascular, high-grade, supratentorial astrocytomas, five were treated with pre-operative radiotherapy alone, and five with radiotherapy in combination with cytostatic drugs. The aim was to investigate the timing of intracranial operations in the multimodality therapy of brain tumors. The tumor size was diminished only in one case, but tumor vascularization was reduced in half of the cases by the pre-operative treatment. Survival was not improved. Surgical treatment still should be the first of the therapeutic measures. Pre-operative radiotherapy may be of value to reduce tumor vascularization in hypervascular, centrally localized tumors.     

Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity

BACKGROUND: We reviewed single-institution experience using brachytherapy alone for primary high-grade soft tissue sarcoma of the extremity. METHODS: Between July 1982 and September 1997, 202 adult patients with primary high-grade soft tissue sarcoma of the extremity were treated with limb-sparing surgery and adjuvant brachytherapy. All patients underwent complete gross resection, but the margin of resection was microscopically positive in 18% of patients. The median dose of brachytherapy was 45 Gy delivered over 5 days. Tumors located in the shoulder or groin were defined as central location. Complications were assessed in terms of wound complications, bone fracture, and peripheral nerve damage. RESULTS: With a median follow-up of 61 months, the 5-year local control, distant relapse-free survival, and overall survival rates were 84%, 63%, and 70%, respectively. On multivariate analysis, poor local control correlated with shoulder location, positive microscopic margins of resection, and nonshoulder upper extremity site. The 5-year actuarial rates of wound complications requiring reoperation, bone fracture, and grade > or = 3 nerve damage were 12%, 3%, and 5%, respectively. CONCLUSIONS: Adjuvant brachytherapy provides adequate local control and acceptable morbidity that compares favorably with data reported for external beam radiation. Shoulder tumor location was identified as an independent prognostic factor for poor local control, mandating further improvement in the local management of these tumors.     

Radiation-associated sarcoma of bone and soft tissue.

Radiation-associated sarcomas are uncommon, constituting less than 5% of all sarcomas, and generally associated with a poor prognosis. We reviewed the medical records of 565 patients with sarcoma and a second malignancy seen at our institution between 1943 and 1989; 160 of these patients (28%) were considered to have a radiation-associated sarcoma. The most common diagnosis for which radiation had been given was breast cancer (26%), followed by lymphoma (25%) and carcinoma of the cervix (14%). The most common histologic types of radiation-associated sarcoma were osteogenic (21%), malignant fibrous histiocytoma (16%), and angiosarcoma/lymphangiosarcoma (15%). Most of the tumors were high grade (87%). Three variables had prognostic significance in multivariate analysis: the presence of metastatic disease, the completeness of operative resection in patients with localized disease, and the size of the primary tumor in patients who underwent complete resection of the sarcoma. Survival was independent of histologic subtype or site of disease.     

Massive allograft implantation following radical resection of high-grade tumors requiring adjuvant chemotherapy treatment

Since 1976, the authors have performed a total of 36 resections of malignant tumors of the limbs with reconstruction of these by implantation of allografts. All allografts have been supplied by the University of Miami Tissue Bank. Following resection of the long-bone tumor and obtaining acceptable margins, the allograft was inserted to the limb defect with three different techniques: (1) in addition to a custom prosthesis as a hemi-joint reconstruction, i.e., a custom Neer prosthesis and proximal humerus allograft; (2) an osteoarticular graft to replace an articular surface resected with the metaphyseal-diaphyseal portion of the tumor; and (3) an intercalary diaphyseal-metaphyseal graft replacing the resected tumor but preserving the recipient articular surface. Of the 36 tumors, one was in Stage III disease. The remainder were Stage II A or B by the System of Enneking. All of these patients had adjuvant chemotherapy. The follow-up time was 24 months to 96 months. The resection of tumors in 36 patients and treatment with postoperative chemotherapy resulted in a mortality of eight out of 36 and one amputation due to recurrence. Satisfactory results were obtained in 19 of 36 patients. If the tumor failures (eight deaths) and the amputation are subtracted from this number, the success rate is 70% (19/27). Intercalary grafts were more successful than osteoarticular grafts. Chemotherapy was started one to two weeks postoperation for all but four patients to whom it was also given preoperation. These patients were in a Children's Cancer Study Group (CCSG) protocol for prospective study of the effects of preoperative chemotherapy. There was no apparent difference in the allograft success in these patients as compared to patients receiving only postoperative chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical treatment for pulmonary artery sarcoma.

OBJECTIVE: Pulmonary artery sarcomas are exceedingly rare and the prognosis for patients with pulmonary artery sarcoma is very poor. We retrospectively reviewed the early and late outcomes after treatment for pulmonary artery sarcoma, and the purpose of this study is to report our surgical experience with this fatal disease. METHODS: Between 1999 and 2007, a total of nine patients (mean age, 47.4 years; M:F = 4:5) underwent operations for pulmonary artery sarcoma at our institution. The tumor was radically resected and every effort was made to remove the tumor as completely as possible. Seven patients underwent surgical resection with the aid of hypothermic cardiopulmonary bypass. The completeness of resection was determined intraoperatively by frozen section biopsy of the resection margin. RESULTS: There was no in-hospital mortality. No patients suffered from significant complications related to the operation. Follow-up was completed for all the patients with a mean duration of 19.2 months. During follow-up, six patients died with a median survival time of 17.6 months. The cause of death was related to the recurrence of pulmonary artery sarcoma in all cases. The pattern of recurrence was local recurrence and distant metastasis in three and four patients, respectively. CONCLUSIONS: The early outcomes after surgical treatment for pulmonary artery sarcoma were excellent, and the late outcomes in this series were no worse than those in the previous reports. We suggest that the use of cardiopulmonary bypass is important to obtain a complete resection and the completeness of the resection should be confirmed intraoperatively by frozen section biopsy of the resection margin.