Prognosis of Primary Osteosarcoma ================================= * Nadja Hamscho * Frank Grünwald **TO THE EDITOR:** We read with interest the article by Franzius et al. (1) dealing with the prognostic significance of 18F-FDG and 99mTc-methylene diphosphonate (MDP) uptake in primary osteosarcoma. The authors examined 29 patients and semiquantitatively measured 18F-FDG and 99mTc-MDP uptake (average and maximum tumor-to-nontumor ratios [T/NTav and T/NTmax, respectively]) using PET and bone scintigraphy at the time of diagnosis. We congratulate the authors on their excellent study. It showed that initial 18F-FDG T/NTmax values clearly discriminated between osteosarcoma patients with a high probability of overall and event-free survival and osteosarcoma patients with a poor prognosis. The authors did not observe a correlation between 99mTc-MDP uptake and prognosis. These results agreed with the reports of another group (2), which could not find any significant relationship at any time between absolute radiopharmaceutical activity within the primary lesion and either disease progression or patient survival. The evaluation of other parameters, such as quantification of perfusion or venous blood pool (vascular and soft-tissue factors), in 3-phase bone scintigraphy could have led to a more specific conclusion about prognosis. Former studies have already shown that the vascular factor is an important predictor of therapeutic response (3,4). A decrease in the tumor–to–blood flow ratio and extension were the most notable findings in responders to chemotherapy. The study showed a significant correlation between 18F-FDG T/NTmax and prognostic outcome. However, it is unfortunate that transmission scanning was not performed in all cases and that consecutive standardized uptake values (SUVs) could not be evaluated sufficiently. This might have provided a prognostically valuable cutoff for SUVs. On the other hand, the comparison of data using tumor-to-nontumor ratios and data using SUVs is limited because tumor-to-nontumor ratios are a less quantitative measurement of tumor 18F-FDG metabolism than are SUVs. In conclusion, we expect that assessment of all available parameters (perfusion, blood pool, mineralization, and glucose consumption) would give the most reliable information for further patient management. ## REFERENCES 1. Franzius C, Bielack S, Flege S, Sciuk J, Jürgens H, Schober O. Prognostic significance of 18F-FDG and 99mTc-methylene diphosphonate uptake in primary osteosarcoma. J Nucl Med. 2002;43:1012–1017. [Abstract/FREE Full Text](http://jnm.snmjournals.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam51bWVkIjtzOjU6InJlc2lkIjtzOjk6IjQzLzgvMTAxMiI7czo0OiJhdG9tIjtzOjIxOiIvam51bWVkLzQ0LzYvOTk2LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 2. Stokkel MPM, Linthorst MF, Borm JJJ, Taminiau AH, Pauwels EKJ. A reassessment of bone scintigraphy and commonly tested pretreatment biochemical parameters in newly diagnosed osteosarcoma. J Cancer Res Clin Oncol. 2002;128:393–399. [PubMed](http://jnm.snmjournals.org/lookup/external-ref?access_num=12136254&link_type=MED&atom=%2Fjnumed%2F44%2F6%2F996.atom) 3. Edeline V, Frouin F, Bazin JP, et al. Factor analysis as a means of determining response to chemotherapy in patients with osteogenic sarcoma. Eur J Nucl Med. 1993;20:1175–1185. [PubMed](http://jnm.snmjournals.org/lookup/external-ref?access_num=8299653&link_type=MED&atom=%2Fjnumed%2F44%2F6%2F996.atom) 4. Ozcan Z, Burak Z, Kumanlioglu K, et al. Assessment of chemotherapy-induced changes in bone sarcomas: clinical experience with 99Tcm-MDP three-phase dynamic bone scintigraphy. Nucl Med Commun. 1999;20:41–48. [PubMed](http://jnm.snmjournals.org/lookup/external-ref?access_num=9949412&link_type=MED&atom=%2Fjnumed%2F44%2F6%2F996.atom) # {#article-title-2} **REPLY:** We appreciate the comments on our article (1) and the opportunity to respond. We agree that changes in blood flow between a pretherapeutic and a posttherapeutic 3-phase bone scan correlate with the response of an osteosarcoma to chemotherapy, as has been demonstrated by several authors. Recent studies suggest that 18F-FDG PET may also be useful for the monitoring of chemotherapy response in osteosarcomas (2,3). Response to neoadjuvant chemotherapy is well know to be an important prognostic parameter in osteosarcoma (4). However, response is a treatment-related variable and not available at initial patient presentation. Therefore, the aim of our study was to evaluate the prognostic significance of 18F-FDG and 99mTc-methylene diphosphonate uptake at the time of diagnosis. In our retrospective analysis, initial 18F-FDG uptake measured by maximum tumor-to-nontumor ratio clearly discriminated between good and poor survival. As the authors of the letter mentioned, it would also be interesting to analyze the prognostic value of tumor perfusion before chemotherapy. To the best of our knowledge, this has not yet been evaluated in osteosarcomas. For technical reasons, no transmission scans were obtained in the first patients examined by 18F-FDG PET. However, attenuation should not play a major role in these young patients, as nearly all primary osteosarcomas were localized in the extremities (with the exception of one pelvic osteosarcoma). Therefore, we could not determine a cutoff standardized uptake value (SUV) between good and poor survival. A recent retrospective study suggested that the 18F-FDG maximum SUV of various sarcomas determined by PET might be an independent predictor of disease progression and survival (5). Therefore, one could hypothesize that 18F-FDG uptake as measured by maximum SUV might also be used to predict prognosis in osteosarcoma. Prospective studies to evaluate this hypothesis are warranted. Furthermore, a possible correlation between 18F-FDG uptake and other well-defined prognostic factors needs to be assessed. ## REFERENCES 1. Franzius C, Bielack S, Flege S, Sciuk J, Jürgens H, Schober O. Prognostic significance of 18F-FDG and 99mTc-methylene diphosphonate uptake in primary osteosarcoma. J Nucl Med. 2002;43:1012–1017. 2. Franzius C, Sciuk J, Brinkschmidt C, Jürgens H, Schober O. Evaluation of chemotherapy response in primary bone tumors with F-18-FDG-PET in comparison to Tc-99m-MDP bone scintigraphy. Clin Nucl Med. 2000;25:874–881. [CrossRef](http://jnm.snmjournals.org/lookup/external-ref?access_num=10.1097/00003072-200011000-00004&link_type=DOI) [PubMed](http://jnm.snmjournals.org/lookup/external-ref?access_num=11079583&link_type=MED&atom=%2Fjnumed%2F44%2F6%2F996.atom) [Web of Science](http://jnm.snmjournals.org/lookup/external-ref?access_num=000165048600004&link_type=ISI) 3. Hawkins DS, Rajendran JG, Conrad EU, Bruckner JD, Eary JF. Evaluation of chemotherapy response in pediatric bone sarcomas by [F-18]-fluorodeoxy-D-glucose positron emission tomography. Cancer. 2002;94:3277–3284. 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