Tumor size as a predictor of outcome in pediatric non-metastatic osteosarcoma of the extremity.
ABSTRACT Better predictors of outcome would allow improved risk-adapted therapy for pediatric nonmetastatic osteosarcoma of the extremity. We investigated the predictive value of MR imaging-based measures of absolute and relative tumor size and volume at the time of diagnosis. We also assessed the relation of tumor size to age and histologic response.
We retrospectively abstracted demographic, treatment history, and outcome information of patients treated on a single institutional protocol. A single pediatric oncologic radiologist manually measured each primary lesion and the affected native bone in three dimensions on MR images obtained at the time of diagnosis. Eight parameters of tumor size were analyzed for their value in predicting overall survival (OS) and event-free survival (EFS).
The median age of the 42 patients was 13.5 years (range: 5.9-18.7 years); 50% were female and 74% were Caucasian. Absolute tumor volume was an important predictor of OS (P < 0.05); absolute tumor depth (analyzed as a continuous variable) was a significant predictor of OS (P = 0.018) and EFS (P = 0.036). Relative measures of tumor size were not found to predict outcome. No relation was seen between tumor size and histologic response.
Absolute tumor size at the time of diagnosis is significantly predictive of OS and EFS. If validated in a larger study, this indicator should be used in the design of risk-adapted treatment protocols for osteosarcoma.
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ABSTRACT: A retrospective multi-institutional study of 227 patients with osteosarcoma of the distal end of the femur was done to compare rates of local recurrence, metastasis, and survival. Three cohorts of patients who had had either a limb-sparing procedure, an above-the-knee amputation, or disarticulation of the hip were compared. The results revealed prevalences of eight of seventy-three, nine of 115, and zero of thirty-nine as to local recurrence; forty-three of seventy-three, sixty-five of 115, and twenty-one of thirty-nine as to metastasis; and thirty-three of seventy-three, forty-eight of 115, and eighteen of thirty-nine as to death. Of the seventeen patients who had a local recurrence, sixteen died. In the limb-salvage group, eighteen patients required amputation, because of local recurrence in eight and other local complications in ten. The Kaplan-Meier estimates of the percentage of patients who survived and the percentage of patients without recurrent disease showed no difference among the three surgical groups (Mantel-Cox test statistic: p = 0.8) after a median length of follow-up of five and one-half years. Various covariant adjusted estimates yielded similar results. For the entire group of patients, the rate of continuously disease-free survival was 42 per cent, and the over-all rate of survival was 55 per cent at five years. It appears that, compared with above-the-knee amputation or disarticulation of the hip, the use of a limb-salvage procedure for osteosarcoma of the distal end of the femur did not shorten the disease-free interval or compromise long-term survival.The Journal of Bone and Joint Surgery 01/1987; 68(9):1331-7. · 3.23 Impact Factor
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ABSTRACT: Many pediatric centers are beginning to accumulate a large experience in the use of thallium-201 (201Tl) imaging with 201Tl requires a state-of-the-art high-resolution gamma camera computer system with single photon emission computed tomography (SPECT) capability and a physician-directed tailored examination. Tumor imaging with 201Tl, with its multifactorial localization mechanisms that are different from those for gallium-67, offers a distinct advantage over gallium tumor imaging with a short total imaging time. Tumors are variable in avidity and intensity of thallium uptake. Primary and metastatic disease can be detected with 201Tl scintigraphy. Baseline pretreatment determination of thallium avidity is crucial to its efficacy in therapeutic response assessment. Adjunctive SPECT imaging provides greater sensitivity for lesion detection and direct comparison of physiology (thallium uptake) with anatomy (computed tomography and magnetic resonance imaging). The sensitivity and specificity for detection of pediatric brain tumors has been reported as 77% and 93%, respectively. Thallium-201 brain SPECT also provides a less expensive and more readily available alternative to positron emission tomography for assessing the functional state of pediatric brain tumors. Extremity osteogenic sarcoma and Ewing's sarcoma have 100% sensitivity for 201Tl uptake pretreatment. Early results confirm an association between 201Tl uptake and histological tumor response. The determination of residual/recurrent disease versus thymic rebound and other nonneoplastic change in thallium-avid lymphoma, rhabdomyosarcoma, and germ cell tumors that involve the thorax can be confirmed with a 201Tl SPECT examination. Soft-tissue tumors elsewhere in the body may be detected with 201Tl scintigraphy. Thallium-201 does not exhibit 100% specificity for tumors. False-positive 201Tl uptake has been seen in histiocytosis X, benign bone tumors, stress fractures, and inflammation.Seminars in Nuclear Medicine 08/1993; 23(3):243-54. · 3.82 Impact Factor
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ABSTRACT: In osteosarcoma, prognostic factors at diagnosis other than clinical stage have not been clearly identified. The aim of this study was to determine whether human epidermal growth factor receptor 2 (HER2)/erbB-2, p-glycoprotein, or p53 expression correlated with histologic response to preoperative chemotherapy or event-free survival. We performed a retrospective immunohistochemical study on material obtained from patients treated on the Memorial Sloan-Kettering Cancer Center T12 protocol between 1986 and 1993. Paraffin-embedded tissue was identified from 53 patients (73% of patients enrolled onto protocol) and stained for HER2/erbB-2, p53, and p-glycoprotein expression using standard monoclonal antibodies and methods. At the time of initial biopsy, 20 (42.6%) of 47 samples demonstrated high levels of HER2/erbB-2 expression. Higher frequencies of expression were observed in samples from patients with metastatic disease at presentation and at the time of relapse. Expression of HER2/erbB-2 correlated with a significantly worse histologic response (P =.03). In patients presenting with nonmetastatic disease, expression of HER2/erbB-2 at the time of initial biopsy was associated with a significantly decreased event-free survival (47% v 79% at 5 years, P =.05). p53 and p-glycoprotein expression did not correlate with histologic response or patient event-free survival. The correlation of HER2/erbB-2 expression with histologic response to preoperative chemotherapy and event-free survival in this study suggests that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator. The correlation also suggests that clinical trials of antibodies that target this receptor, such as recombinant humanized anti-HER2 monoclonal antibody (Herceptin; Genentech, San Francisco, CA), should be considered for the treatment of osteosarcoma.Journal of Clinical Oncology 10/1999; 17(9):2781-8. · 18.04 Impact Factor