Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma.

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P <.01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.     

A comparison of staging systems for localized extremity soft tissue sarcoma

BACKGROUND: Staging systems for soft tissue sarcoma (STS) are important to identify patients with similar systemic risk who might benefit from specific treatments. This study compared four commonly used staging systems for predicting systemic outcomes of patients with localized extremity STS, as proposed by the fourth and fifth editions of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, the Memorial Sloan-Kettering Cancer Center (MSK) system, and the Surgical Staging System (SSS) of the Musculoskeletal Tumor Society. METHODS: Three hundred consecutive adult patients with newly diagnosed nonmetastatic STS of the lower extremity were treated at Memorial Sloan-Kettering Cancer Center between 1982 and 1989. Metastasis free survival was the end point of the study. The prognostic value of the four staging systems and their components were examined in univariate and multivariate analyses. The Akaike information criterion (AIC) was used to identify the system that best predicted the risk of systemic recurrence. RESULTS: Compartment status, depth, grade, and size were all independent predictors of outcome within their respective staging systems. However, when compared with one another, only depth, grade, and size retained their prognostic significance. Of the four models, the AIC predicted that the MSK was the best predictor of systemic relapse, followed by the fifth edition of the AJCC/UICC staging system. CONCLUSIONS: Staging systems such as the MSK system or the fifth edition of the AJCC/UICC system, which include tumor depth, grade, and size as prognostic factors, are the most predictive of systemic relapse in patients presenting with localized extremity STS. Both of these systems identify the same group of patients at the highest risk who would be the most suitable for adjuvant chemotherapy trials.     

Proliferative activity (ki-67 expression) and outcome in high grade osteosarcoma: a study of 27 cases

Purpose. Although pre-operative chemotherapy has improved the prognosis for individuals with osteosarcoma, approximately 40% of patients will die of their disease.The aim of this study was to quantitate proliferative activity in high grade osteosarcomas and to determine whether proliferation is a prognostic factor.Patients. The study consisted of 27 patients with high grade non-metastatic osteosarcoma at various sites for whom pre-operative biopsies and resection specimens were available for review. All patients were treated similarly and had at least 24 months' follow-up from the date of diagnosis.Methods. Proliferative activity (Ki-67 expression) was examined in the diagnostic biopsies immunohistochemically using the MIB-1 antibody. Proliferation was quantitated in two ways; (1) the number of immunopositive cells was counted manually using an ocular grid; or (2) the percentage of immunopositive nuclear area was assessed using morphometric image analysis. Proliferative index was evaluated in relation to patient outcome.Results. Proliferative activity was seen in all biopsies.The median proliferative index as determined by counting cells was 24% (mean of 27%, range of 7-61%) and by image analysis was 2% (mean 3%, range 0.32-8.4).The correlation between MIB-1 proliferation indices determined either by image analysis methodology or manual cell counting was high (Spearman's rho=0.79). Proliferative index did not appear to predict either disease-free or overall survival.Discussion. Tumor proliferation does not appear to be prognostic for high grade osteosarcomas.Whether assessment of this feature in conjunction with other tumor characteristics might be prognostic requires further study.     

Lymph node metastasis in soft tissue sarcoma in an extremity

For patients with soft tissue sarcoma in an extremity, the outcome is thought to be poor if lymph node metastasis develops. The purpose of this study was to examine the impact of lymphatic involvement from soft tissue sarcoma on patient survival. Thirty-nine (3.7%) of 1066 patients who had surgery for soft tissue sarcoma in an extremity had lymph node metastases develop. Three (20%) of 15 patients with epithelioid sarcoma, four (19%) of 21 patients with rhabdomyosarcoma, two (11.1%) of 18 patients with clear cell sarcoma, and two (11.1%) of 18 patients with angiosarcoma had lymphatic involvement. Thirty patients who had resection of involved lymph nodes had an estimated 5-year survival of 57%, whereas nine patients treated without surgery all died within 30 months. An estimated 4-year survival of 71% for patients with isolated lymph node metastases was significantly better than 21% for patients with synchronous systemic and lymph node involvement. There was no difference in outcome for patients with isolated lymphatic involvement compared with patients with American Joint Committee on Cancer Stage III extremity sarcomas. These results suggest that long-term survival is possible after surgical resection of lymphatic metastases from soft tissue sarcoma. The American Joint Committee on Cancer should consider separating isolated nodal metastases from systemic involvement in patients with Stage IV sarcoma.     

Primary synovial osteochondromatosis of the hip: extracapsular patterns of spread

Objective To identify patterns of extracapsular extension of synovial osteochondromatosis of the hip.Design and patients Seven cases of synovial osteochondromatosis of the hip were retrospectively reviewed. Imaging performed included conventional radiography (n=7), arthrography (n=1), CT (n=3) and MR imaging (n=3). Disease extent on imaging was assessed for each patient and the presence of intra-articular effusion, capsular abnormality and osteochondral bodies recorded. The presence and distribution of extra-articular spread was also assessed and correlated with the surgical findings. In all cases diagnosis was confirmed by biopsy, with all patients undergoing tumor resection with or without synovectomy.Results In five cases (5/7) disease extended beyond the hip capsule, while the remaining two cases (2/7) were confined to the hip joint. These findings were confirmed at surgery. Two distinct patterns of extracapsular spread were identified. The first pattern, noted in three cases, involved tumor extension along iliopsoas. The second pattern, noted in five cases, involved tumor extension along the obturator externus fat plane. In three cases both patterns were present.Conclusions Extra-articular spread of synovial osteochondromatosis is common. Patterns of extra-articular spread may be predictable based on involvement of recognized periarticular bursae of the hip joint. Bursal patterns of extra-articular spread include extension into the iliopsoas bursa as well as communication along the obturator externus bursa of the hip.     

Transarticular invasion of bone tumours across the sacroiliac joint

Purpose The purpose of this study was to evaluate the pattern of tumour spread across the SI articulation, correlating with cadaveric anatomic observations, in order to better understand the local spread of tumour and to assist in the assessment of local staging. Material and methods Twenty-four consecutive patients (14 male, 10 female; age range 22–89 years, mean 52 years) with primary bone tumours of the iliac bone or sacrum abutting the SI joint, in whom surgical resection of the SI joint was performed, were studied following institutional ethics approval. In all patients, preoperative magnetic resonance (MR) imaging studies of the pelvis and SI joint were reviewed for imaging evidence of transarticular extension across the SI joint. Gross pathologic and histologic assessment of possible transarticular SI joint tumour extension was performed in all patients. Nine cadaveric pelvic specimens without pelvic neoplastic disease (4 male, 5 female; age range 20–84 years, mean 59 years, median 58 years) were anatomically dissected and the articular anatomy of the SI joint examined macroscopically. Results Twelve of the twenty-four patients demonstrated imaging and histological evidence of transarticular SI joint invasion. Eight tumours infiltrated only the interosseous ligamentous aspect of the SI joint. In the remaining four cases, extensive tumour infiltrated both the cartilaginous and ligamentous aspects of the joint. No case showed tumour involvement isolated to the cartilaginous aspect of the joint. Among the cadaveric specimens studied, degenerative changes were found involving the majority of cases (6/9), with cartilage thinning and fibrillation and antero-superior marginal osteophytes seen involving the cartilaginous portion of the SI joint articulation. Four of the nine specimens demonstrated central ossification bridging the iliac and sacral aspects of the ligamentous (interosseous) SI joint. Conclusion Tumour invasion across the SI articulation favours its interosseous ligamentous portion. Factors influencing transarticular tumour extension and its preferential course across the interosseous component of the articulation have been discussed. It is particularly important to assess the interosseous ligamentous portion of the SI articulation when locally staging primary pelvic bone tumours subjacent to the SI articulation, as this will have a significant impact on planning surgical management.     

Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma.

BACKGROUND AND PURPOSE: This study compared late radiation morbidity in patients with extremity soft tissue sarcoma randomized to treatment by pre- (50 Gy) or postoperative (66 Gy) radiotherapy in combination with surgery. The morbidities evaluated included fibrosis, joint stiffness and edema at 2 years following treatment. The impact of morbidity on patient function as measured by the Musculoskeletal Tumor Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS) was also evaluated. PATIENTS AND METHODS: 129 patients were evaluated. Toxicity rates were compared by treatment arm using the Fisher's exact test. Function scores by toxicity were analyzed using the Wilcoxon rank sum test. Multivariate logistic regression was used to evaluate the joint effect of treatment arm, field size, and dose on subcutaneous tissue fibrosis, joint stiffness and edema. RESULTS: 27 of 56 patients (48.2%) in the postoperative arm compared to 23 of 73 (31.5%) in the preoperative arm had grade 2 or greater fibrosis (P = 0.07). Although not statistically significant, edema was more frequent in the postoperative arm, 13 of 56 (23.2%) versus 11 of 73 (15.5%) in the preoperative arm, as was joint stiffness, 13 of 56 (23.2%) versus 13 of 73 (17.8%). Patients with significant fibrosis, joint stiffness or edema had significantly lower function scores on both measures (all P-values < 0.01). Field size was predictive of greater rates of fibrosis (P = 0.002) and joint stiffness (P = 0.006) and marginally predictive of edema (P = 0.06). CONCLUSIONS: Patients treated with postoperative radiotherapy tended to have greater fibrosis. Fibrosis, joint stiffness and edema adversely affect patient function.     

Eosinophilic granuloma. A different behaviour in children than in adults

Localised Langerhans-cell histiocytosis of bone (eosinophilic granuloma) is a benign tumour-like condition with a variable clinical course. Different forms of treatment have been reported to give satisfactory results. However, previous series all contain patients with a wide age range. Our aim was to investigate the effect of skeletal maturity on the rate of recurrence of isolated eosinophilic granuloma of bone excluding those arising in the spine. We followed up 32 patients with an isolated eosinophilic granuloma for a mean of five years; 17 were skeletally immature. No recurrences were noted in the skeletally immature group even after biopsy alone. By contrast, four of 13 skeletally mature patients had a recurrence and required further surgery. This suggests that eosinophilic granuloma has a low rate of recurrence in skeletally immature patients.