Limb salvage management of pathologic fractures of primary malignant bone tumors.

BACKGROUND: Little is known about oncologic outcomes of patients with primary bone tumors complicated by a pathologic fracture and treated by limb salvage. METHODS: Our study included 17 men and 14 women aged 6 to 61 years (average age 17 years). All 31 patients had primary bone tumors complicated by a pathologic fracture. Diagnoses included osteosarcoma (17 patients), Ewing's sarcoma (10), malignant fibrous histiocytoma (3), and lymphoma (1). All received preoperative chemotherapy. The distal femur was affected in 13 patients, the proximal femur in 6, mid shaft femur in 4, the proximal humerus in 4, the proximal tibia in 3, and the fibula in 1. All patients underwent limb salvage and achieved a wide resection margin. RESULTS: The average follow-up period was 18 months (range 8 to 51 months). Two patients required amputation due to local recurrence. Six patients developed pulmonary metastases and eventually died. CONCLUSIONS: A pathologic fracture of primary bone tumor is not always a contraindication for limb salvage since the oncologic outcome appears acceptable.     

Limb preservation surgery with extracorporeal irradiation in the management of malignant bone tumor: the oncological outcomes of 101 patients

BackgroundEn bloc resection, extracorporeal irradiation (ECI) and reimplantation have been used selectively at our centers as part of limb preservation surgery of malignant bone tumors since 1996. We report the long-term oncological outcomes.Patients and methodsOne hundred one patients were treated with ECI at two Australian centers between 1996 and 2011. A single dose of 50 Gy was delivered to the resected bone segments. The irradiated bones were reimplanted immediately as a biological graft. Patients were treated with chemotherapy as per standard protocol. The three main histological diagnoses were Ewing's sarcoma (35), osteosarcoma (37) and chondrosarcoma (20). There were nine patients with a range of different histologies.ResultsThere was one local recurrence (2.86%) in Ewing's sarcoma and the 5-year cumulative overall survival was 81.9%. There was no local recurrence in osteosarcoma and five distant recurrences. The 5-year cumulative overall survival was 85.7%. The local recurrence rate was 20% (4 of 20) in chondrosarcoma, and the 5-year cumulative overall survival was 80.8%. Limb preservation was achieved in 97 patients. For the 64 patients with disease in the pelvis or lower limb, 53 (82.3%) could walk without aids at the time of last follow-up.ConclusionsThis large series of ECI shows an excellent long-term local control. It is a good alternative reconstruction method in selected patients. The overall survival is comparable to other published series.     

Secondary tumors in bone sarcomas after treatment with chemotherapy.

New oncologic treatments have improved survival in osteosarcoma and Ewing's sarcoma. However, these treatments may cause secondary malignancies after radiotherapy. This study evaluated the incidence of secondary malignancies after neoadjuvant chemotherapy. Between April 1972 and December 1990, 518 osteosarcoma and 299 Ewing's sarcoma patients entered neoadjuvant chemotherapy protocols. Follow-up records of all patients were analyzed and malignant tumors were reported. Nine patients developed another malignancy, including 5 leukemias, 1 astrocytoma, 1 liposarcoma, 1 parotid, and 1 breast carcinoma. Four leukemias were found in patients treated for osteosarcoma with chemotherapy, but not radiotherapy. Only one leukemia developed after Ewing's sarcoma treated with chemotherapy and radiotherapy. The incidence of leukemias is high, while the other tumors can be explained as unrelated cases. Incidence densities for leukemia were calculated for both groups of patients. Treated osteosarcoma patients seem to have a predisposition to develop leukemias, but whether this is chemotherapy induced needs to be investigated.     

Periosteal Ewing's sarcoma

Ewing's sarcoma is a small cell malignant tumor that usually arises in the medullary cavity of bone. Less frequently, it originates in soft tissue and may secondarily invade underlying bone. The origin of Ewing's sarcoma in a periosteal location without extension into either the bone or adjacent soft tissue has not been clearly documented. Other malignant tumors of bone (e.g., osteosarcoma) appear to have a somewhat better prognosis when confined between periosteum and bone. The case of a patient with a periosteal Ewing's sarcoma who received a radical excision and postoperative chemotherapy and who is without evidence of disease with over 2 years follow-up is reported.     

肢体骨恶性肿瘤首次诊疗失误患者的挽救治疗

背景与目的：恶性骨肿瘤发病率较低，仅占人类全部恶性肿瘤的1％左右，临床中出现误诊误治的现象很多。本研究在分析21例肢体骨恶性肿瘤首诊失误原因的基础上．探讨挽救治疗的方法及其疗效。方法：回顾性分析我院1998年10月-2005年12月间收治的21例首次诊疗失误的肢体骨恶性肿瘤患昔的临床资料及平均随访22个月（6—67个月）的随访结果。其中骨巨细胞瘤（GCT）3例，骨肉瘤12例．尤文氏肉瘤1例，恶性纤维组织细胞瘤3例，骨纤维肉瘤1例，恶性骨母细胞瘤1例。21例中，2例误诊为“骨囊肿”行病灶刮除植骨；19例误诊为“骨髓炎”行病灶刮除，3例加用灌洗引流。结果：11例保留肢体的患者，按Enneking的骨肿瘤外科治疗后功能评定标准，优良率72．7％（8／11）。广泛性截肢10例，11例保肢后再哉肢5例，除GCT外均辅以化疔死亡8例（38．1％）．存活13例（占61．9％），其中4例为带瘤存活。结论：恶性骨肿瘤的诊治要强调首次诊疗的正确性及规范性，建立完善的转诊制度是减少治疗失误的有效途径。对于首次诊疗失误的患者．推荐以手术及化疗为主的综合治疗，慎用保肢术。     

Chemotherapy in the management of osteosarcoma and Ewing's sarcoma

Sarcomas of bone are rare malignancies diagnosed in fewer than 3000 individuals yearly in the United States. Ewing's sarcoma and most osteosarcoma are high-grade neoplasms and account for approximately one half of bone sarcoma cases. Fewer than 20% of patients presenting with localized Ewing's sarcoma or osteosarcoma are cured with surgery alone. Current management typically involves collaboration among orthopedic oncologists, medical oncologists, musculoskeletal radiologists, sarcoma pathologists, and radiation oncologists. Modern multidisciplinary management of Ewing's sarcoma and osteosarcoma has improved the cure rate of patients with localized disease to more than 50%. Primary chemotherapy for high-grade bone sarcomas often involves intensive, multiagent regimens, and few secondary chemotherapy options are available to treat refractory or relapsed disease. Patient participation in clinical trials of novel therapies for Ewing's sarcoma and osteosarcoma should be strongly encouraged.     

Autologous bone marrow transplantation in pediatric cancer

Since May 1979, 47 patients with pediatric malignancy aged 1 to 18 years (median: 7) were treated with cryopreserved autologous bone marrow transplantation (ABMT) in the department of pediatrics, National Cancer Center Hospital. The malignancies were acute non-lymphocytic leukemia (n = 8), acute lymphocytic leukemia (n = 5), osteosarcoma (n = 7), neuroblastoma (n = 6), brain tumor (n = 5), rhabdomyosarcoma (n = 4), retinoblastoma (n = 3), Ewing's sarcoma (n = 3), non-Hodgkin's lymphoma (n = 2), malignant histiocytosis (n = 1), hepatoblastoma (n = 1), malignant melanoma (n = 1) and malignant neuroepithelioma (n = 1). Conditioning regimens for solid tumors were multi-agent high-dose chemotherapy, mainly consisted of cyclophosphamide (CY) 120 mg/kg or melphalan 180mg/m2 and that for hematological malignancies were CY with fractionated total body irradiation (12 Gy). In vitro purging by 4-hydroperoxycyclophosphamide was performed in 12 leukemia patients and 5 solid tumor patients. Of the 13 patients with acute leukemia, 1 died from relapse 1 year after the unpurged marrow transplantation and 1 relapsed in the testis. Remaining 11 patients are alive in continuous complete remission with a median follow up of 30 months (range, 2 to 65 months) after transplantation. The disease-free survival rate of them was 78%. Of the 34 patients with solid tumor, 21 patients died, their cause of death were relapse in 18 and each one of infection, graft failure and brain hemorrhage. Thirteen patients are alive without disease with a median follow up of 28 months (range, 2 to 107 months) posttransplant. The longest survivor is a brain tumor girl, and there are 5 other long survivors; 2 of them are osteosarcoma and each one of rhabdomyosarcoma, Ewing's sarcoma and malignant histiocytosis. The disease-free survival rate of total 34 solid tumor patients is 29%, but that of 17 patients who received ABMT in responsive and minimum tumor residue (MTR) period was 69%. These results suggest that autologous bone marrow transplantation is an effective and tolerable treatment for poor prognostic pediatric malignancies, especially for acute leukemia and such solid tumor as that in MTR state.     

The role of radiation treatment in the contemporary management of bone tumors

Radiotherapy is integral in the multidisciplinary approach to patients with musculoskeletal neoplasms. Multiple studies have established a role for radiotherapy as a definitive local treatment of unresectable lesions or when surgery might yield unacceptable functional outcomes, such as in Ewing's tumor or base of skull chondrosarcoma. Radiotherapy is also used as an adjuvant treatment after surgery with close or positive margins. In the metastatic setting, external beam radiotherapy and bone-seeking intravenous radioisotopes are used on a case-by-case basis for palliation. As radiotherapy and its delivery techniques have evolved, so has its role in treating tumors such as Ewing's sarcoma, chordoma and chondrosarcoma, osteosarcoma, primary lymphoma of bone, malignant fibrous histiocytoma of bone, and vascular tumors. Radiation can also be successfully used to treat unresectable or recurrent benign tumors, such as giant cell tumor and aneurysmal bone cyst. This article reviews the indications for radiotherapy for various bone tumors and summarizes some of the important data supporting its use.     

四肢恶性骨肿瘤切除后骨缺损使用异体骨移植术重建修复的疗效

目的:研究同种异体骨移植术修复重建四肢恶性骨肿瘤切除后骨缺损的临床疗效。方法:选取2016年03月至2019年08月我院收治的四肢恶性骨肿瘤切除后骨缺损行同种异体骨移植重建修复的患者15例和行复合肿瘤型人工关节置换的患者9例;本文研究对象均经穿刺活检和术后病理确诊;Enneking分期Ⅰb期6例,Ⅱb期18例;术前尤文肉瘤3例和骨肉瘤15例患者均行2个疗程化疗和术后规范化疗;应用MSTS评价术后患者的肢体功能情况。结果:所有患者均获得随访,随访时间为8~46个月,平均（29.63±11.21）个月;24例患者术后均未发生假体周围骨折或移植异体骨折,且无假体松动和关节脱位;20例患者术后肢体功能优良,MSTS评分为16~28分,平均（22.80±4.46）分。结论:四肢恶性骨肿瘤切除术后骨缺损使用异体骨段移植重建长骨干缺损和或肿瘤型人工关节复合置换治疗的临床疗效显著。     

Intraoperative Radiotherapy in the Multidisciplinary Treatment of Pediatric Tumors a Preliminary Report on Initial Results

From September 1984 to July 1987, 33 children received intra-operative radiotherapy as part of a multidisciplinary tumor treatment. Their age ranged from 2 to 17 years. Tumors types: Ewing's sarcoma (n=11), osteosarcoma (n=8), soft tissue sarcomas (n=5), Wilms' tumor (n=3), neuroblastoma (n=3), malignant pheochromocytoma (n=l), Hodgkin's disease (n=1), and optic nerve glioma (n=1). In 25 patients the disease was localized while 8 had distant metastases. Intraoperative radiotherapy was used in 26 previously untreated patients as part of a radical treatment program and in 7 cases as an effort to rescue local failures (5 in previously irradiated areas). The intraoperative radiation field included the surgically exposed tumor or tumor bed, and the single doses ranged from 10 to 20 Gy, with 6-20 MeV electrons. Patients with osteosarcoma and recurrent tumor in a previously irradiated area did not receive postoperative external beam radiotherapy. With a median follow-up time of 10 months (1 to 31+months) 24 out of 33 patients are alive without local recurrence and 9 have died from tumor (5 with local disease progression). Intraoperative radiotherapy seems to be a feasible treatment which might promote local control in pediatric tumors.     

Malignancy in giant cell tumor of bone

BACKGROUND: The term malignant giant cell tumor embraces multiple entities and therefore can be confusing. The goals of the current study were to define the clinicopathologic and histologic features of malignancy in giant cell tumors and to clarify the terminology. METHODS: The authors reviewed all cases from the Rizzoli Institute (Bologna, Italy) of primary (PMGCT) and secondary (SMGCT) malignancy in giant cell tumors. PMGCT is a high-grade sarcoma that arises side by side with benign giant cell tumors. SMGCT is a high-grade sarcoma that occurs at the sites of previously treated giant cell tumors of bone. RESULTS: The authors report 5 PMGCTs and 12 SMGCTs; half of the SMGCTs were postradiation sarcomas. Patient age ranged from 20 to 68 years (median, 62 years) for PMGCT and from 30 to 77 years (median, 40 years) for SMGCT. The average latent period between diagnosis of giant cell tumor and diagnosis of SMGCT was 9 years (range, 3-15 years) for patients with postradiation SMGCT and 19 years (range, 7-28 years) for patients with SMGCT resulting from spontaneous transformation. The histologic classification of high-grade sarcomas in the PMGCT group was osteosarcoma in four cases and malignant fibrous histiocytoma in one case. In the SMGCT group, the histologic classification was osteosarcoma in nine cases, fibrosarcoma in two cases, and malignant fibrous histiocytoma in one case. The outcomes associated with all malignancies in giant cell tumors were poor, with the worst outcome associated with postradiation SMGCT. CONCLUSIONS: Malignancies in giant cell tumors of bone always are high-grade sarcomas with a poor prognosis. These lesions must be distinguished from benign giant cell tumors of bone. SMGCT usually is easy to diagnose upon malignant clinicoradiographic presentation. In contrast, PMGCT often mimics giant cell tumors both clinically and radiographically. In addition, upon histologic examination, PMGCT shows areas of conventional giant cell tumor, which can lead to difficulties in making the correct diagnosis.     

Primary bone and joint tumor--statistical analysis of 571 cases

This paper analyses 571 cases of primary bone and joint tumors diagnosed by histopathology, excluding the tumor-like lesions. They were divided into two groups: the benign (412 cases, 72.15%) and the malignant (159 cases, 27.85%). The susceptible ages were between 15-29 years and the susceptible location of these tumors were femur and tibia often on the right side. There were more males than the females. The frequencies in the two groups are as follows: In the benign group, osteoma had the highest incidence and then, with decreasing frequencies: osteochondroma, chondroma, synovioma, giant cell tumor, ossifying fibroma, osteoid osteoma, chondromyxoid fibroma. In the malignant group, the highest incidence was in the osteosarcoma, and then synoviosarcoma, chondrosarcoma, malignant giant cell tumor, Ewing's tumor, fibrosarcoma, osteomyeloma. The sequence of the incidence was basically similar to that reported abroad and at home. The pathogenesis of several kinds of bone tumor are discussed.     

单纯髂骨切除术治疗髂骨原发恶性骨肿瘤

目的：探讨单纯髂骨切除术治疗髂骨原发恶性肿瘤的手术方法,分析其肿瘤学结果及骶髂关节连续性对患者肢体功能的意义。方法回顾分析1983年6月至2011年6月,诊断为髂骨原发恶性肿瘤并于我院骨肿瘤科行单纯髂骨切除术且资料完整的患者25例。分析该术式对髂骨恶性肿瘤的治疗效果及手术后骶髂关节连续性对患者肢体功能的影响。结果25例均于我院进行手术治疗,男19例,女6例。病例分布为软骨肉瘤13例,骨肉瘤6例,尤文肉瘤2例,梭形细胞肉瘤2例,未分化多形性肉瘤2例。随访14.2～127.9个月,平均41个月。截止随访期末,18例未发现肿瘤复发或转移。1例骨肉瘤患者于术后9个月出现肺转移,行胸腔镜肺部病灶切除,1例尤文肉瘤患者术后58个月出现肺部转移,行化疗,1例软骨肉瘤患者术后23个月出现局部复发,再次手术切除,此3例目前均存活。4例死亡,1例骨肉瘤患者术后10个月出现肺部转移,术后18个月死亡;1例软骨肉瘤患者术后12个月出现肺部转移,术后15个月死亡;1例术后29个月发现局部复发及肺部转移,术后39个月死亡;1例骨肉瘤患者术后26个月因肝功能衰竭死亡。15例可行MSTS评分系统进行评分,平均为27.5（24～30）分。其中10例骶髂关节连续性存在,MSTS评分平均为28.8分,5例骶髂关节连续性破坏,MSTS评分为25.0分。结论单纯髂骨切除术是治疗髂骨原发恶性肿瘤的有效术式,骶髂关节失去连续性对行走功能有一定影响。其功能可满足日常生活需要。     

Extraskeletal osteosarcoma

A retrospective study of 88 cases of extraskeletal osteosarcoma revealed that this tumor affects adults almost exclusively, with a high incidence in patients older than 50 years, and is slightly more common in males (58%) than in female patients. The tumor occurred principally as a soft tissue mass in an extremity, with a predilection for the thighs (lower extremity, 46.6%; upper extremity, 20.5%) and the retroperitoneum (17%). Most were deep-seated and were firmly attached to the fascia, but occasionally they were freely movable and confined to the subcutis or dermis. Nearly all presented as an insidiously growing mass rarely causing pain or tenderness. The preoperative duration of symptoms ranged from 2 weeks to 25 years (median, 6 months). In 17 cases, it exceeded 2 years. A history of prior trauma to the site of the tumor was stated in 11 of the 88 cases (12.5%) and of radiation in five cases (5.7%). Microscopically, the tumors contained varying amounts of neoplastic osteoid and bone, sometimes together with islands of malignant-appearing cartilage. Like osteosarcoma of bone, extraskeletal osteosarcoma showed a striking variation in histologic appearance and focally resembled malignant fibrous histiocytoma, fibrosarcoma, and malignant schwannoma. Follow-up information was available for 65 patients. Eight (12.3%) patients were alive with no evidence of recurrence; 12 (18.5%) patients were alive with one or more recurrences; and five (7.6%) were alive with metastases. Twenty-eight of the tumors (43%) recurred and 39 (63%) metastasized. Forty (61.5%) of the patients with follow-up information had died, 36 from the tumor and four from miscellaneous causes. The prevailing sites of metastases were the lung, the regional lymph nodes, and bone.     

Evidence-based chemotherapy for patients with bone and soft part sarcoma

In the present paper, we review the evidence for chemotherapy in patients with bone and soft part sarcoma and discuss the contributions and improvements made by chemotherapy to the treatment of patients with bone and soft part sarcoma. In the osteosarcoma and Ewing's sarcoma family, neoadjuvant and adjuvant chemotherapy have improved the 5-year disease-free survival to 60%, and limb-salvage operations have improved this to 70-80% in cases of non-metastatic malignant bone tumor. Several trials were conducted in order to overcome rate relapses and metastatic bone sarcoma. With osteosarcoma, thoracotomy improved the survival of lung metastatic patients, but CDDP-ADM branch switched according to the neoadjuvant chemotherapy and failed to elevate the continuous disease-free survival of patients. Dose intensive use of cytotoxic drugs with G-CSF or autologous bone marrow transplantation and multidrug programs were conducted in preliminary studies and achieved favorable results in a high risk factors group for tumors of the Ewing's sarcoma family. Surgical techniques have brought improvements in the treatment of soft tissue sarcoma, but there has been no impact by chemotherapy. Ifosfamide and adriamycin combination is being evaluated in the treatment of local advanced and metastatic soft part sarcoma by local control rate or survival from relapse.     

Effectiveness of Ecteinascidin-743 against drug-sensitive and -resistant bone tumor cells.

PURPOSE: The identification of new drugs is strongly needed for bone tumors.Ecteinascidin-743 (ET-743), a highly promising antitumor agent isolated from the marine tunicate Ecteinascidia turbinata, is currently under Phase II clinical investigation in Europe and the United States for treatment of soft tissue sarcoma. In this study, we analyzed the preclinical effectiveness of this drug in osteosarcoma and Ewing's sarcoma. EXPERIMENTAL DESIGN: The effects of ET-743 were evaluated against a panel of human osteosarcoma and Ewing's sarcoma cell lines characterized by different drug responsiveness and compared with the effects of standard anticancer agents. In addition, combination treatments with ET-743 and the other standard chemotherapy agents for sarcoma were analyzed to highlight the best drug-to-drug interaction RESULTS: A potent activity of ET-743 was clearly observed against both drug-sensitive and drug-resistant (multidrug-resistant, methotrexate- and cisplatin-resistant) bone tumor cells at concentrations that are easily achievable in patients (pM to nM range). Ewing's sarcoma cells appeared to be particularly sensitive to the effects of this drug. The analysis of the effects of ET-743 on cell cycle, apoptosis, and differentiation indicated that both osteosarcoma and Ewing's sarcoma cells had a slower progression through the different phases of the cell cycle after treatment with ET-743. However, the drug was able to induce a massive apoptosis in Ewing's sarcoma but not in osteosarcoma cells. In the latter neoplasm, ET-743 showed a differential effect, as indicated by the significant increase in the expression and activity of alkaline phosphatase, a marker of osteoblastic differentiation. Concurrent exposure of cells to ET-743 and other chemotherapeutic agents resulted in greater than additive interactions when doxorubicin and cisplatin were used, whereas subadditive effects were observed with methotrexate, vincristine, and actinomycin D. CONCLUSIONS: Overall, these results encourage the inclusion of this drug in the treatment of patients with bone tumors, although a careful design of new regimens is required to identify the best therapeutic conditions.     

Subsequent Malignant Neoplasm of Bone in Children and Adolescent—Possibility of Multimodal Treatment

Background: In recent years, modifications of treatment protocols introduced in pediatric oncology have resulted in a significant improvement in treatment outcomes. Unfortunately, the probability of subsequent malignant neoplasm (SMN) in this group of patients is 3 to 6 times higher than the general age-matched population. In this study, we sought to evaluate the treatment options for patients with secondary bone tumors after prior anti-cancer therapy. Materials and Methods: Twenty-four patients (median age 12.9 years) with subsequent malignant bone tumors were treated according to oncological guidelines for bone sarcoma during the period 1991–2020. All patients had a standard tumor imaging and laboratory evaluation. All toxicities were documented. Results: The median time from the first neoplasm to SMN was 7.6 years (range 2.4 to 16.3 years). All patients received chemotherapy and underwent surgery as a local control procedure. Two patients with Ewing sarcoma had additional radiation on the tumor bed. A complete response was achieved in 20 patients. With a median follow-up of 18.3 years (range 5.7 to 40.3 years), 18 patients (75%) are alive. The estimated 5-year post-subsequent bone malignant neoplasm survival was 74.5% (95% CI 55–95%). Fourteen patients required chemotherapy dose modification, and doxorubicin was discontinued in seven patients. One patient required a renal transplant two years after treatment. There were no other significant toxicities. Conclusions: The treatment of bone SMNs can be effective, although in many patients it is necessary to reduce the doses of drugs. Early detection and aggressive treatment can improve the outcome.     

Late effects of radiotherapy for pediatric extremity sarcomas

PURPOSE: To determine the long-term effects of radiotherapy (RT) in children treated for extremity sarcoma. PATIENTS AND METHODS: Between 1964 and 1997, 15 of 33 children treated with RT for extremity sarcomas at the University of Iowa have survived with a median follow-up was 20 years (range, 6-36 years). There were 10 boys and 5 girls with a median age of 13 years (range, 3.5-20 years) at the time of irradiation. The diagnosis was Ewing's sarcoma in 8 (53%), synovial sarcoma in 4 (27%), alveolar rhabdomyosarcoma in 2, and fibrosarcoma in 1. Location of primary tumor was lower extremity in 10 (67%) and upper extremity in 5 (33%). RT was given as the definitive therapy for 9 children (median dose, 55.8 Gy; range, 45-66 Gy) and as an adjuvant postoperative treatment in 6 (median, 63 Gy; range, 41.4-66.4 Gy). (60)Co was used in 6 (40%), 4 mV in 4, 6 mV in 2, and 250 kV photons in 2 patients; 1 child was treated with a combination of 12 and 15 MeV electrons for a Ewing's sarcoma of the distal femur. Another child had a 25 Gy intraoperative RT boost after 41.4 Gy conventional RT. Late effects to the muscle, soft tissue, and growing bone were assessed using the objective portion of the LENT-SOMA scale proposed by the Late Effects Consensus Conference. RESULTS: Late effects were seen in all patients and included atrophy in 12 (80%), fibrosis in 12 (80%), bone growth abnormalities in 10 (67%), impairment of mobility and extremity function in 6 (40%), edema in 3 (20%), and peripheral nerve injury in 2 (13%). Ten of 15 (67%) children had Grade 1 or 2 growing bone, muscle, soft tissue, or peripheral nerve complications. Two patients (13%) had a Grade 3 mobility and extremity function score and had moderate to severe limitation of movement. Two children (13%) required epiphysiodesis because of a shorter treated leg. The patient who received an intraoperative RT boost of 25 Gy developed sensory dysfunction of the ulnar nerve 11 years after RT. Another developed radial nerve palsy 3 years after marginal resection and postoperative RT and required tendon transfer repair. One patient had radiation-induced vasculitis with popliteal artery thrombosis 23 years after RT. Five (33%) developed a fracture of the irradiated bone at a median time of 8 years after RT (range: 9 months to 22.2 years); all had Ewing's sarcoma, and 3 of these patients were subsequently found to have a secondary bone cancer (osteosarcoma 2, malignant fibrous histiocytoma 1) in the RT field. One of these patients also developed breast cancer 26 years after lung RT for metastatic Ewing's sarcoma. Overall, 11 surgical procedures in 8 children were performed to correct a limb preservation treatment toxicity. CONCLUSIONS: Although most children treated with RT for a pediatric extremity sarcoma have minimal late toxicity by LENT-SOMA scale, approximately half required a surgical procedure to correct a late effect. A fracture in the irradiated bone may be the presenting sign or may precede a radiation-induced bone malignancy, as seen in 3 of the patients in this study.     

Second solid malignancies among children, adolescents, and young adults diagnosed with malignant bone tumors after 1976: follow-up of a Children's Oncology Group cohort

BACKGROUND: The growing number of individuals surviving childhood cancer has increased the awareness of adverse long-term sequelae. One of the most worrisome complications after cancer therapy is the development of second malignant neoplasms (SMNs). METHODS: The authors describe the incidence of solid organ SMN in survivors of pediatric malignant bone tumors who were treated on legacy Children's Cancer Group/Pediatric Oncology Group protocols from 1976 to 2005. This retrospective cohort study included 2842 patients: 1686 who were treated for osteosarcoma (OS) and 1156 who were treated for Ewing sarcoma (ES). RESULTS: The cohort included 56% boys/young men and 44% girls/young women, and the median age at primary diagnosis was 13 years. The median length of follow-up was 6.1 years (range, 0-20.9 years). In this analysis, 64% of patients were alive. Seventeen patients with solid organ SMN were identified. The standardized incidence ratio was 2.9 (95% confidence interval [CI], 1.4-5.4) for patients who were treated for OS and 5.0 (95% CI, 2.6-9.4) for patients who were treated for ES. The median time from diagnosis to development of solid SMN was 7 years (range, 1-13 years). The 10-year cumulative incidence of solid organ SMN for the entire cohort was 1.4% (95%CI 0.6%-2%). CONCLUSIONS: The magnitude of risk of solid SMNs was modest after treatment for malignant bone tumors. However, radiation-related solid SMNs will increase with longer follow-up. Because nearly 33% of patients die from their disease, recurrence remains the most significant problem. The development of improved therapies with fewer long-term consequences is paramount. Follow-up should focus on monitoring for both recurrence of primary malignancies and development of SMNs.     

Blood serum somatomedin activity in children with bone tumors

Blood somatomedin levels were assayed biologically in 10 children with Ewing's sarcoma and osteosarcoma and 11 children with other benign tumors. The patients were of the same age. The basal level of somatomedin in malignant bone sarcoma was similar to that in controls. However, after glucose loading, the patterns of somatomedin level curve in children and adults with normal lipo-carbohydrate metabolism were different. The difference may be due either to the specific features of child's organism or a rise in the level of blood somatomedin inhibitors.