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Background: The current standard for neoadjuvant chemotherapy (NACT) response evaluation in osteosarcoma is histopathologic necrosis (HN). However, it is accessible only after NACT completion and may get affected by confounding factors. Thus, noninvasive surrogate such as (18)Fluorine-Fluorodeoxyglucose-positron emission tomography-computerized tomography (PET-CT) scan would be useful to individualize therapy., Methods: Thirty-one treatment naive osteosarcoma patients evaluated prospectively by PET-CT scan preceding and after 3 cycles of NACT and surgery during 2006 to 2008. Various anatomic and metabolic parameters of PET-CT scan were compared with HN (good response ≥90% HN) as reference standard. Receiver operating characteristic curves were generated to assess the best threshold and predictability., Results: Median age was 17 years; 25 were male patients and 23 were nonmetastatic. Ten cases were good, whereas 21 cases were poor histologic responders. PET-CT parameters including post-NACT (2) and pre-NACT (1) standard uptake value (SUV)max ratio (SUV2:SUV1), SUV2, pre-NACT and post-NACT volumes (V1and V2), change in V after NACT, pre-NACT and post-NACT metabolic burden (MB) and change in MB after NACT correlated with HN. Two independent predictors were identified in stepwise multivariable analysis; if V1 ≤300 mL and SUV2:SUV1 ≤0.48, observed good histologic response proportions was 83%, whereas if V1 >300 mL and SUV2:SUV1 >0.48, it was 0%., Conclusions: NACT response can be predicted reliably by PET-CT scan early in disease course (even at baseline) and PET-CT parameters correlate well with HN. MB seems to be sensitive substitute for response evaluation. Independent predictors may have wider clinical applications if further validation can be done.

Background: There is controversy regarding the patterns and prognostic significance of Her-2/neu and p-53 expression in osteosarcoma. Further, their combined expression has not been studied., Procedure: Prechemotherapy biopsy specimens of 63 osteosarcoma patients from June 2004 to August 2006 were analyzed for Her-2/neu and p-53 using immunohistochemistry and compared with grade, stage, and morphologic subtype of tumor., Results: There were 59 high-grade tumors; 32 of 63 had metastases. Histopathologic types included 36 of 63 osteoblastic and 18 of 63 chondroblastic subtypes. Male sex (P=0.045) and chondroblastic type (P=0.004) were associated with metastatic disease. Her-2/neu cytoplasmic staining was seen in 30 of 63 (47.1%) cases, 4 of 30 had additional membranous staining, 17 of 30 were metastatic, and 29 of 30 were high-grade tumors. Staining grade was 3+ in 10 of 30 samples whereas staining intensity 3+ was observed in 26 of 30 samples. Her-2/neu 3+ staining grade was significantly associated with chondroblastic subtype (6/18, P=0.026). P-53 staining was seen in 20 of 63 (31.74%) cases (all high grade), of which 11 were metastatic. Staining grades 3+ and 4+ were seen in 16 of 20 samples whereas staining intensity 3+ in 13 of 20 samples. P-53 expression was higher in chondroblastic (7/18, P value was not significant) and fibroblastic (3/3, P<0.05) subtypes. Coexpression of Her-2/neu and p-53 was seen in 10 cases (15.87%); 3 of 10 cases showed Her-2/neu membranous staining (P=0.01)., Conclusions: Her-2/neu (47.1%), p-53 (31.74%), and their combined expression (15.87%) were not related to grade or stage of tumor. Chondroblastic subtype was associated with staining grade 3+ of Her-2/neu staining whereas coexpression of Her-2/neu and p-53 was significantly associated with membranous Her-2/neu staining.

Background: Skeletal metastases of bone sarcomas are indicators of poor prognosis. Various imaging modalities are available for their identification, which include bone scan, positron emission tomography/CT scan, MRI, and bone marrow aspiration/biopsy. However, there is considerable ambiguity regarding the best imaging modality to detect skeletal metastases. To date, we are not sure which of these investigations is best for screening of skeletal metastasis.Question/purpose: Which staging investigation-18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT), whole-body MRI, or 99mTc-MDP skeletal scintigraphy-is best in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in detecting skeletal metastases in patients with osteosarcoma and those with Ewing sarcoma?Methods: A prospective diagnostic study was performed among 54 of a total 66 consecutive osteosarcoma and Ewing sarcoma patients who presented between March 2018 and June 2019. The institutional review board approved the use of all three imaging modalities on each patient recruited for the study. Informed consent was obtained after thoroughly explaining the study to the patient or the patient's parent/guardian. The patients were aged between 4 and 37 years, and their diagnoses were proven by histopathology. All patients underwent 99mTc-MDP skeletal scintigraphy, 18F-FDG PET/CT, and whole-body MRI for the initial staging of skeletal metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were determined and compared with each other. Multidisciplinary team meetings were held to reach a consensus about the total number of metastases present in each patient, and this was considered the gold standard. The sensitivity, specificity, PPV, and NPV of each imaging modality, along with their 95% confidence intervals, were generated by the software Stata SE v 15.1. Six of 24 patients in the osteosarcoma group had skeletal metastases, as did 8 of 30 patients in the Ewing sarcoma group. The median (range) follow-up for the study was 17 months (12 to 27 months). Although seven patients died before completing the minimum follow-up, no patients who survived were lost to follow-up.Results: With the number of patients available, we found no differences in terms of sensitivity, specificity, PPV, and NPV among the three staging investigations in patients with osteosarcoma and in patients with Ewing sarcoma. Sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 67% (4 of 6 [95% CI 22% to 96%]) and specificities were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 78% (14 of 18 [95% CI 52% to 94%]), respectively, in patients with osteosarcoma. In patients with Ewing sarcoma, sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 88% (7 of 8 [95% CI 47% to 100%]), 88% (7 of 8 [95% CI 47% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and specificities were 100% (22 of 22 [95% CI 85% to 100%]), 95% (21 of 22 [95% CI 77% to 100%]), and 95% (21 of 22 [95% CI 77% to 100%]), respectively. Further, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and the NPVs were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 88% (14 of 16 [95% CI 62% to 98%]), respectively, in patients with osteosarcoma. Similarly, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (7 of 7 [95% CI 59% to 100%]), 88% (7 of 8 [95% CI 50% to 98%]), and 80% (4 of 5 [95% CI 28% to 100%]), and the NPVs were 96% (22 of 23 [95% CI 78% to 100%]), 95% (21 of 22 [95% CI 77% to 99%]), and 84% (21 of 25 [95% CI 64% to 96%]), respectively, in patients with Ewing sarcoma. The confidence intervals around these values overlapped with each other, thus indicating no difference between them.Conclusion: Based on these results, we could not demonstrate a difference in the sensitivity, specificity, PPV, and NPV between 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy for detecting skeletal metastases in patients with osteosarcoma and Ewing sarcoma. For proper prognostication, a thorough metastatic workup is essential, which should include a highly sensitive investigation tool to detect skeletal metastases. However, our study findings suggest that there is no difference between these three imaging tools. Since this is a small group of patients in whom it is difficult to make broad recommendations, these findings may be confirmed by larger studies in the future.Level Of Evidence: Level II, diagnostic study. [ABSTRACT FROM AUTHOR]