Stereotactic radiosurgery for primary and metastatic sarcomas involving the spine.

The treatment for spinal sarcomas is difficult due to inadequate surgical margin and an inability to deliver high dose radiation. Advanced technology of stereotactic radiosurgery (SRS) enabled higher biological effective doses of radiation to be delivered to spinal sarcomas by hypofractionation method. The authors evaluated local control rate following SRS for primary and metastatic spinal sarcomas. Thirty-two spinal sarcomas (10 primary tumors, 22 metastatic tumors) in 27 patients were treated by SRS from November 2002 to September 2009. Patients were assessed for pain status, neurological status and radiological response by regular follow-up. Overall survival and local progression-free survival were calculated and prognostic factors were sought. Median tumor volume was 18.6 ml. Radiation doses to the tumor margins ranged from 16 to 45 Gy in one to three fractions, and the median single session equivalent dose was 21.8 Gy. Follow-up ranged from 4 to 68 months (median, 22 months). Overall median survival was 29 months and no related prognostic factors were identified. During follow-up, pain was controlled in 89.3% (25/28) lesions at 6 months, in 68.2% (15/22) at 1 year, and in 61.5% (8/13) at 2 years. Tumor volume was found to be significantly related to post-SRS pain control rate. Radiological evaluation showed that local control was maintained in 96.7% (29/30) lesions at 6 months, in 78.3% (18/23) at 1 year, and in 76.9% (10/13) at 2 years. Radiation dose and tumor volume were found to be related to radiological control at 24 months following SRS. Nine cases developed recurrence between 2 and 33 months, median local progression-free survival was 23 months. Age was found to be predictive of local progression-free survival (P = 0.009). SRS proved to be an effective modality for the local control of primary and metastatic spinal sarcomas, and age was significantly related to local recurrence.

Prognostic nomogram for predicting the 5-year probability of developing metastasis after neo-adjuvant chemotherapy and definitive surgery for AJCC stage II extremity osteosarcoma.

BACKGROUND: In this retrospective study, we developed and internally validate a nomogram for predicting 5-year metastasis probability for nonmetastatic extremity osteosarcoma. PATIENTS AND METHODS: We reviewed 365 osteosarcoma patients treated at our institute from 1990 to 2003. Clinicopathologic variables were recorded. Multivariate analysis using Cox proportional hazards regression was done and this Cox model was used as the basis for the nomogram. RESULTS: By American Joint Committee on Cancer (AJCC) staging system, 141 patients (38.6%) were stage IIA and 224 (61.4%) were stage IIB. Multivariate Cox model identified patient age at diagnosis, tumor size, humeral location, and tumor necrosis rate after chemotherapy as correlated with metastasis-free survival. The degree of contribution of each covariate to the total point was tumor location, tumor necrosis rate, maximal tumor diameter, and age in decreasing order. The concordance index for the model was 0.78. Nomogram discrimination was superior to that of AJCC stage (concordance index 0.78 versus 0.68; P = 0.02) and histologic response grouping (concordance index 0.78 versus 0.69; P = 0.0004). CONCLUSIONS: We devised a nomogram for nonmetastatic osteosarcoma that proposes improved estimates of metastasis over AJCC staging system or tumor necrosis rate. We suggest that this nomogram allows individualized risk assessments and could be used as the basis for risk-adapted therapy.

Overlapping allograft in reconstructive surgery for malignant bone tumours in paediatric patients: a preliminary report.

The use of allografts for the treatment of bone tumours in children is limited by nonunion and the difficulty of finding a suitable graft. Furthermore, appositional growth can't be expected of an allograft. We used an overlapping allograft in 11 children, with a mean age of ten years (4 to 15), with a mean follow-up of 24.1 months (20 to 33). There were five intercalary and six intra-articular resections, and the tumours were in the femur in six cases and the humerus in five. Rates of union, times to union, remodelling patterns and allograft-associated complications were evaluated. No allograft was removed due to a complication. Of the 16 junctional sites, 15 (94%) showed union at a mean of 3.1 months (2 to 5). Remodelling between host and allograft was seen at 14 junctions at a mean of five months (4 to 7). The mean Musculoskeletal Tumor Society score was 26.5 of 30 (88.3%). One case of nonunion and another with screw protrusion required re-operation. Overlapping allografts have the potential to shorten time to union, decrease rates of nonunion and have positive appositional growth effect.

Prognosis of extremity osteosarcoma in patients aged 40-60 years: a cohort/case controlled study at a single institute.

BACKGROUND: The outcome of older osteosarcoma patients with multi-disciplinary management has not been clearly defined. METHODS: We conducted a cohort (n=375) and a case-control (n=78) study on 26 older age patients (40-60 years) with localized osteosarcoma of extremity. In the case-control study, controls were matched for location and initial tumor volume. RESULTS: Compared to 349 younger patients, older age patients showed an osteolytic pattern on plain radiographs (P=0.05), fibroblastic subtype (P<0.01), and poor histologic response (P=0.03). Multivariate analysis revealed that a large absolute tumor volume (P<0.01), a tumor location in the proximal humerus (P=0.02), and a poor histologic response to preoperative chemotherapy (P<0.01) independently predicted poorer metastasis-free survival. However, an older age showed marginal significance (P=0.09). A case-control study showed a higher proportion of the fibroblastic subtype and poor histologic response in the case group. Five-year metastasis-free survival rates for the 26 cases and 52 controls were 40.1+/-10.1% and 61.5+/-6.8%, respectively (P=0.02). CONCLUSIONS: Older age osteosarcoma patients showed an unfavorable histologic response to chemotherapy and lower survival than younger patients. Nevertheless, a further larger-scale study is required to confirm our observations.

Synovial sarcoma of the extremities.

From May 1985 to March 1990, 18 cases of Enneking's stage II synovial sarcoma of the extremities were treated by a combination of surgery and CYVADIC chemotherapy with or without radiotherapy. The average follow up was 34.7 months. The estimated 5-year survival rate was 78.4% and the continuously disease-free 5-year survival rate was 44.4%. The results were improved by adequate surgery or chemotherapy when local recurrence or metastases had developed. The combination of surgery and CYVADIC chemotherapy with or without radiotherapy was considered to be an effective method of treating this tumour.

Malignant fibrous histiocytoma of the limbs.

Between June 1985 and May 1990 we treated 12 patients with malignant fibrous histiocytoma (MFH) of the limbs by a combination of wide excision and adjuvant radiotherapy. The Enneking surgical staging was II in 11 cases and III in 1. There were 6 women and 6 men, with an average age of 54 years. The leg was involved in 8 patients and the arm in 4. Limb salvage was achieved in 10 patients and amputation was performed in 2. All received adjuvant radiotherapy, with an average of 51.5 Gy. In 6 patients adjuvant CYVADIC chemotherapy was administered for an average of 4 cycles. In the other patients this treatment was not tolerated. Local recurrence occurred in 2 patients and metastases to the lung were seen in a further 2. At an average follow-up of 41.3 months, the Kaplan-Meier estimation of 5 year survival was 87.5%, with a 5 year continuous disease-free survival rate of 66.7%.

Algorithm for the surgical treatment of malignant lesions of the proximal tibia.

Complications are common among patients treated for malignant lesions of the proximal tibia and can be difficult to manage. This investigation was a retrospective review of 40 patients treated with total knee replacements after proximal tibial resections. Various reconstructive methods were used to fix the prosthetic stems, reestablish the extensor mechanism, and provide soft tissue coverage. Thirty-one patients had adequate followup to allow for review of prosthetic outcome (means, 78 months; range, 25-193 months). Seven patients died with less than 2 years followup, and two patients had postoperative acute infections treated by early amputation to allow chemotherapy to resume promptly. The overall 5-, 8-, and 12-year event free prostheses survival rates were 62%, 33%, and 16%, respectively. Prognostic factors for prosthetic survival were analyzed (age, gender, type of excision, type of prosthesis, type of fixation, and percent of bone resected). None were statistically significant. Patients with less than 40% of the tibia resected had better prosthetic survival at 5 years. The durability of uncemented stem fixation exceeded that of cemented stems. Expected survival of prostheses after revision was 52% at 8 years. The major cause of limb loss was infection. Failure to reconstruct soft tissues satisfactorily caused most failures. Aggressive multistage management of infection is needed. Prosthetic knee replacement is most suitable for patients with cancers that require chemotherapy and for those patients who have short potential survival.

A rotating-hinge knee replacement for malignant tumors of the femur and tibia.

We evaluated the 2- to 7-year results of a rotating-hinge knee replacement after excision of malignant tumors of the knee joint. There were 25 distal femoral and 7 proximal tibial replacements. The 5-year prosthetic survival for distal femoral replacements was 88%, compared with 58% for proximal tibial replacements. Seven patients underwent prosthetic exchange: 1 for aseptic loosening, 2 for wound slough and perioperative infection, and 4 for articulating component failure. One patient underwent above-knee amputation owing to skin necrosis. The median functional scores at the latest follow-up were 27 by the International Society of Limb Salvage evaluation system and 80 by the Hospital for Special Surgery Knee Score system. This implant is a promising choice for joint reconstruction after excision of tumors at the knee joint.

Pathological responses to preoperative high-dose methotrexate chemotherapy in osteosarcoma--experience in Korea cancer hospital.

During the last decade, many clinical investigators at various cancer centers have reported the efficacy of various chemotherapeutic agents in the treatment of osteosarcoma. The regimens using high-dose methotrexate (HDMTX) with citrovorum factor rescue are now considered to be one of the most effective treatments of choice. From December 1989 to May 1991, sixteen patients with Enneking's stage (Enneking et al., 1980) IIB osteosarcoma of the extremities were treated with a high-dose methotrexate regimen. After two cycles of preoperative chemotherapy, an operation was performed; either limb salvage or amputation. The resected lesions were examined pathologically and classified according to Huvos' criteria. On pathological examination, 8 (50%) cases showed Grade IV; 1 (6.25%) Grade III; 4 (25%) Grade II; and 3 (18.75%) Grade I. The types of surgery performed were tumor prosthesis replacement (11); wide resection with or without reconstruction (2); resection and arthrodesis (1); and amputation (2).

Deletion of Rb1 gene in late osteosarcoma from survivor of unilateral retinoblastoma--a case report.

It has been well known that the survivors of retinoblastoma are prone to have osteosarcoma. But the secondary tumor usually occurs in bilateral, hereditary type of retinoblastoma. We report one case of osteosarcoma in a survivor of unilateral, sporadic retinoblastoma. A fourteen year old male presented with a painfully swollen distal forearm of 2 month duration. He had enucleated his left eye 10 years ago due to retinoblastoma with no other adjuvant therapy. We managed him with our conventional protocol and identified deletion of Rb gene from his pathological specimen by using the PCR-RFLP method. This result is unusual for unilateral nonhereditable retinoblastoma and may suggest gene level change even in sporadic cases. And Rb gene study may be helpful for unilateral, sporadic retinoblastoma patient in detecting the possibility of late osteosarcoma.

Enhanced expression of cathepsin L in metastatic bone tumors.

Cathepsin L is a kind of cystein proteases which are known to facilitate the invasion and metastasis of tumor cells by degrading the components of basement membrane and extracellular matrix. This study was undertaken to investigate the expression of cathepsin L by Northern blot analysis with radiolabeled cDNA specific for cathepsin L in six normal tissues, two osteosarcoma cell lines, MG-63 and Saos-2, six primary bone tumors and six metastatic bone tumors. In six normal tissues, the highest level of cathepsin L was expressed in liver with the descending order of liver > lung > thymus > ovary > kidney > esophagus. One of the two osteosarcoma cell lines established from the primary sites expressed a high level of cathepsin L mRNA. Out of six primary bone tumors, three (50%) expressed cathepsin L mRNA, while all (100%) of six metastatic bone tumors expressed the mRNA. These results demonstrating the higher frequency of expression of cathepsin L in metastatic bone tumors suggest that cathepsin L may participate in tumor invasion and metastasis.