Robert Turcotte

Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial

BACKGROUND External-beam radiotherapy (delivered either preoperatively or postoperatively) is frequently used in local management of sarcomas in the soft tissue of limbs, but the two approaches differ substantially in their potential toxic effects. We aimed to determine whether the timing of external-beam radiotherapy affected the number of wound healing complications in soft-tissue sarcoma in the limbs of adults. METHODS After stratification by tumour size (< or = 10 cm or >10 cm), we randomly allocated 94 patients to preoperative radiotherapy (50 Gy in 25 fractions) and 96 to postoperative radiotherapy (66 Gy in 33 fractions). The primary endpoint was rate of wound complications within 120 days of surgery. Analyses were per protocol for primary outcomes and by intention to treat for secondary outcomes. FINDINGS Median follow-up was 3.3 years (range 0.27-5.6). Four patients, all in the preoperative group, did not undergo protocol surgery and were not evaluable for the primary outcome. Of those patients who were eligible and evaluable, wound complications were recorded in 31 (35%) of 88 in the preoperative group and 16 (17%) of 94 in the postoperative group (difference 18% [95% CI 5-30], p=0.01). Tumour size and anatomical site were also significant risk factors in multivariate analysis. Overall survival was slightly better in patients who had preoperative radiotherapy than in those who had postoperative treatment (p=0.0481). INTERPRETATION Because preoperative radiotherapy is associated with a greater risk of wound complications than postoperative radiotherapy, the choice of regimen for patients with soft-tissue sarcoma should take into account the timing of surgery and radiotherapy, and the size and anatomical site of the tumour.

Giant cell tumor of long bone: a Canadian Sarcoma Group study.

A multicentric retrospective study of giant cell tumor of bone was conducted among Canadian surgeons. The hypothesis was that no differences would be found in health status, function, or recurrence rate irrespective to the nature of filling material or adjuvant used in patients treated with curettage. One hundred eighty-six cases were collected. There were 96 females and 90 males. The mean age of the patients was 36 years (range, 14–72 years), the minimum followup was 24 months, and the median followup was 60 months. Sixty-two percent of the tumors involved the knee region. One hundred fifty-eight were primary tumors and 28 were recurrences. Campanacci grading was as follows: Grade 1, seven patients; Grade 2, 100 patients; Grade 3, 76 patients; and unknown in three patients. Fifty-six patients had a pathologic fracture. Resection was done in 38 patients and 148 patients had curettage. The latter was supplemented with high speed burring in 135 patients, cement in 64 patients, various combinations of autograft or allograft bone in 61 patients, phenol in 37 patients, and liquid nitrogen in 10 patients. Structural allografts were used in 25 patients. The overall recurrence rate was 17%, 18% after curettage, and 16% after resection. Patients with primary tumors treated with curettage had a 10% recurrence rate. For recurrent lesions treated by curettage, the recurrence rate was 35%. The nature of the filling material used or the type of adjuvant method used or any combination of both failed to show any statistical impact on the recurrence risk. The results from the Musculoskeletal Tumor Society rating from 1987 were significantly lower in patients who sustained a displaced fracture. Results from the bodily pain section of the Short Form-36 also were found to be lower when a pathologic fracture was present. Results from the Musculoskeletal Tumor Society Rating 1987, the Short Form-36, and the Toronto Extremity Salvage Score did not show differences when either cement or bone graft were used after curettage.

FDG PET/CT imaging in primary osseous and soft tissue sarcomas: a retrospective review of 212 cases

PurposeThe aims of this study are to evaluate the sensitivity of FDG PET/CT for detection of soft tissue and osseous sarcomas on the basis of FDG avidity.MethodsWe retrospectively evaluated 212 consecutive patients with known soft tissue or osseous sarcoma who had undergone a FDG PET/CT study for the initial staging or assessment of recurrence of disease. The maximum standardized uptake value (SUVmax) of each primary and/or most intense metastatic lesion was measured and compared with the histological data provided in the final pathological reports. An SUVmax of 2.5 or greater was considered positive for our analysis.ResultsSufficient histopathological data were available for 160 soft tissue sarcomas and 52 osseous sarcomas. FDG PET/CT detected 93.9% of all sarcomas with a sensitivity of 93.7% for soft tissue sarcomas and 94.6% for osseous sarcomas. The sensitivities of the most common sarcoma histologies were 100% for leiomyosarcomas, 94.7% for osteosarcomas, 100% for Ewing’s sarcomas, 88.9% for liposarcomas, 80.0% for synovial sarcomas, 100% for gastrointestinal stromal tumors, 87.5% for malignant peripheral nerve sheath tumors, 100% for fibroblastic and myoblastic sarcomas, and 100% for malignant fibrohistiocytic tumors. The receiver-operating characteristic curve revealed an area under the curve of 94% for the discrimination of low-grade and high-grade sarcomas imaged for initial staging by FDG PET/CT.ConclusionThe combined metabolic and morphological information of FDG PET/CT imaging allows high sensitivity for the detection of various sarcomas and accurate discrimination between newly diagnosed low-grade and high-grade sarcomas.

Outcome after pelvic sarcoma resection reconstructed with saddle prosthesis.

We retrospectively reviewed 27 patients who had saddle prosthetic reconstruction for pelvic sarcoma from 1991 to 2001 with a mean followup of 45 months. Functional outcome was assessed with Musculoskeletal Tumor Society Scores of 1987 and 1993 and the Toronto Extremity Salvage score. Survival, recurrences, and complications were recorded. Seven (26%) patients had Type II (periacetabular) pelvic resection and 20 had Types II and III (periacetabular and pubis) pelvic resection. Eleven patients had chemotherapy treatment. None received radiation therapy. At final followup 14 patients were free of disease, 11 patients died, and two patients were alive with disease. The survival rate was 60%. Twenty-two percent had local recurrence, and 22% had metastasis. The mean Musculoskeletal Tumor Society Score 93 score in 17 patients was 50.8% ± 21.7%, the mean Musculoskeletal Tumor Society Score 87 score was 15.3 ± 6.1, and the mean Toronto Extremity Salvage score was 64.4% ± 17.2%. Infection occurred in 10 patients; six were deep infections. There were five nerve palsies. Heterotopic ossification occurred in 10 patients, fracture occurred in six patients, and dislocation occurred in six patients. Limb shortening was progressive until it stabilized at 12 months, and ultimately ranged between 1 and 6 cm. Five patients were retired, five had full-time employment, and six were disabled. Reconstruction with the saddle prosthesis after resection for pelvic sarcoma is associated with substantial morbidity. However, the functional results seem to confer an advantage when compared with the considerable disability incurred after hemipelvectomy. Level of Evidence: Therapeutic study, Level IV-1 (case series without control group). See the Guidelines for Authors for a complete description of levels of evidence.

FDG PET/CT in Initial Staging of Adult Soft-Tissue Sarcoma

Soft-tissue sarcomas spread predominantly to the lung and it is unclear how often FDG-PET scans will detect metastases not already obvious by chest CT scan or clinical examination. Adult limb and body wall soft-tissue sarcoma cases were identified retrospectively. Ewings sarcoma, rhabdomyosarcoma, GIST, desmoid tumors, visceral tumors, bone tumors, and retroperitoneal sarcomas were excluded as were patients imaged for followup, response assessment, or recurrence. All patients had a diagnostic chest CT scan. 109 patients met these criteria, 87% of which had intermediate or high-grade tumors. The most common pathological diagnoses were leiomyosarcoma (17%), liposarcoma (17%), and undifferentiated or pleomorphic sarcoma (16%). 98% of previously unresected primary tumors were FDG avid. PET scans were negative for distant disease in 91/109 cases. The negative predictive value was 89%. Fourteen PET scans were positive. Of these, 6 patients were already known to have metastases, 3 were false positives, and 5 represented new findings of metastasis (positive predictive value 79%). In total, 5 patients were upstaged by FDG-PET (4.5%). Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging as part of the initial staging of soft-tissue sarcomas was unlikely to alter management in our series.

Radiological and pathological response following pre-operative radiotherapy for soft-tissue sarcoma

PURPOSE To report radiological and pathological response to neo-adjuvant radiotherapy for extremity and trunk soft-tissue sarcomas. MATERIALS/METHODS Fifty patients were identified retrospectively. All patients had MRI imaging pre and post neo-adjuvant external beam radiotherapy. Tumor volumes were measured in 3D on T1 Gadolinium enhanced sequences. Pathological treatment response was quantified in terms of percentage of treatment-related necrosis for each case. RESULTS Histopathologic responses to treatment varied from 0% to 100%. The median pathological treatment response was 67.5% for low-grade sarcomas and 50% for high-grade sarcomas. The median decrease in tumor volume was 13.8% for non-myxoid low-grade sarcomas, 82.1% for myxoid liposarcomas and <1% for high-grade sarcomas. A partial response on MRI (volume reduction ≥50%) was highly predictive of a good pathological response (p<0.001). Patients with stable disease on imaging or volumetric progression had wide ranging pathological responses. CONCLUSIONS Soft-tissue sarcomas show significant pathological treatment responses in the form of hyaline fibrosis, necrosis and granulation tissue. Despite this, there is minimal early volumetric response to radiation, especially for high-grade tumors. Although radiological partial response was predictive of pathological response, the significance of radiological progression was unclear. Myxoid liposarcoma tumor type was predictive of both pathological and radiological tumor response.

Cemented rotating hinge endoprosthesis for limb salvage of distal femur tumors.

We retrospectively ascertained the outcomes and complications with a cemented rotating hinge implant. Implant failure was defined as amputation of the affected limb and revision of part or all of the components. We included 77 consecutive distal femoral replacements performed between 1989 and 2004. The mean age was 42 years (range, 12-87 years) and the mean length of followup was 52 months (range, 1.5-157 months). Five-year implant survival was 84% and 10-year survival was 79%. There were 67 bone sarcomas, two soft tissue sarcomas and eight metastatic carcinomas. At followup, 54 patients had no evidence of disease, 16 were alive with disease, and seven were dead from disease. Six patients had deep infection, two of which required amputations. There were five local recurrences; three needed amputation and two soft-tissue excisions only. Three patients sustained a tibial bearing fracture and one required replacement of loose bumper. No revision was performed for stem loosening, stem fracture, or bushing wear. Musculoskeletal Tumor Society 1987 scores averaged 30 and Toronto Extremity Salvage Scores averaged 77.6 at latest followup. Cemented endopros- thesis is a reliable procedure after resection of the distal femur for tumors.Level of evidence: Therapeutic study, level IV (case series). See Guidelines for Authors for a complete description of levels of evidence.

Function and health status in surgically treated bone metastases.

In a prospective study, we evaluated if surgery substantially improved functional and quality of life outcomes in patients with nonspinal bone metastases. Sixty-seven patients were followed up prospectively. The Short Form-36, the Musculoskeletal Tumor Society 1987 form, the Musculoskeletal Tumor Society 1993 form, and the Toronto Extremity Salvage Score were administered preoperatively and 6 weeks and 3 months postoperatively. Fifty percent of the patients had pathologic fractures. Intramedullary nailing was done in 36 patients, prosthetic replacement was done in 24 patients, and plating was done in five patients. The average postoperative survival was 8 months. At 6 weeks, 13 patients had died and seven were lost to followup. Twenty-one percent of patients had complications, although only 4.5% needed additional surgery. The patients’ Musculoskeletal Tumor Society 1987 form, Musculoskeletal Tumor Society 1993 form, and Toronto Extremity Salvage Score scores improved at 6 weeks and 3 months postoperatively. There were no improvements in the Short Form-36 mental and physical summary scales of the patients. The number of patients using pain medication did not decrease. Patients had functional improvements after surgical treatment of bone metastases, even patients with a limited life expectancy. Future prospective studies should anticipate a high rate of attrition with this population from death and loss to followup. Level of Evidence: Prognostic study, Level I (high quality prospective study—all patients were enrolled at the same point in their disease with ≥ 80% followup of enrolled patients). See the Guidelines for Authors for a complete description of levels of evidence.

Experience with cemented large segment endoprostheses for tumors.

Published reports dealing with tumor prosthesis have yet to establish a clear advantage of using either cemented or cementless implants. We examined the outcome and complications with modular cemented implants in 135 patients identified from our database to strengthen the argument for routine use of cemented constructs. The minimum followup was 1.4 months (mean, 57 months; median, 47 months; range, 1.4-157 months). The majority of patients (104) had sarcoma. The complications included: 11 infections, three of which underwent amputation and one a stem revision; eight local recurrences, five of which underwent amputation; three hip dislocations; and three incidents of shoulder instability. One periprosthetic femur fracture was stabilized operatively. There was no aseptic loosening or stem fracture. The 5-year survival rates for distal femoral and proximal humeral replacements were 84% and 70%; the 10-year survival rates were 79% and 59%. The 5-year survival rates for proximal femur and proximal tibia replacements were 78% and 37%. Average Musculoskeletal Tumor Society 1987 scores and Toronto Extremity Salvage Scores were 21.5 and 73% for proximal femur, 28.1 and 67% for distal femur, and 21 and 78% for proximal humerus. The survival of the endoprostheses related to site of bone resection. Cemented constructs of modern design in the context of tumor surgery provide good short-term results.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Functional evaluation in distal femoral endoprosthetic replacement for bone sarcoma

A multicenter study of successfully treated patients (mean age, 36.7 years) with a minimum 1-year followup (average, 35.4 months) after distal femoral endoprosthetic replacement for bone sarcoma was done using the 1987 and 1993 versions of the Musculoskeletal Tumor Society, the Short Form-36, and the Toronto Extremity Salvage Score functional evaluation criteria. Fifty-six patients (28 women and 28 men) fulfilled the criteria. Thirty-one Kotz prostheses (fixed hinge, uncemented) and 25 Modular Replacement System Prostheses (rotating hinge, cemented) were used. Thirty-five patients walked without aids, 19 used a cane, and two used crutches or a walker. The Musculoskeletal Tumor Society 1987 mean score was 28.1. The Musculoskeletal Tumor Society 1993 mean score was 80.4. The Toronto Extremity Salvage Score mean was 81.6. The Short Form-36 Physical Component Score had a mean of 43.2 and Mental Component Score mean of 54.2. The two groups of implants were comparable, except for the length of bone resection. Multivariate regression analysis revealed that patient age, existence of a pathologic fracture, and type of prosthesis all significantly accounted for differences in functional outcome as measured by the Musculoskeletal Tumor Society 1993, the Toronto Extremity Salvage Score, and the Short Form-36 Physical Component Score scales. Although both implants provided satisfactory function, the Musculoskeletal Tumor Society 1993 and the Toronto Extremity Salvage Score results were significantly better with the Modular Replacement System prosthesis. The effect of possible differences among surgeons or institutions was not addressed.