Abstract
Purpose
The utility of combined metabolic and volumetric 18F-FDG PET/CT indices for predicting tumour necrosis fractions following neoadjuvant chemotherapy has not been extensively studied in osteosarcoma. Furthermore, little is known of the early PET/CT responses after only one chemotherapy course.
Methods
Enrolled in the study were 20 children and young adults with resectable osteosarcoma who had undergone 18F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Maximum standardized uptake value (mSUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. From among the 20 patients, 14 were prospectively recruited and underwent an additional PET/CT scan after one chemotherapy course. Histopathological necrosis fractions were compared with the above-mentioned PET/CT indices and their ratios.
Results
MTV at the SUV threshold of 2 g/ml was closely correlated with the magnetic resonance image volumes before therapy (r = 0.91). In the prospective cohort, five patients were classified as good responders and nine as poor responders. All the metabolic indices (mSUV and its ratio) and combined metabolic/volumetric indices (MTV, TLG, and their ratios) except the mSUV ratio determined after therapy showed significant differences between good and poor responders (P <0.05). Differences were also noted for all of these indices determined after one chemotherapy course. Furthermore, most of these indices determined after therapy as well as after one chemotherapy course had good sensitivity, specificity, positive predictive value and negative predictive value with respect to predicting histological response to chemotherapy.
Conclusion
In our osteosarcoma patient population, 18F-FDG PET/CT indices (either combined metabolic/volumetric or metabolic indices) determined after neoadjuvant chemotherapy were useful in predicting tumour responses. This held true after only one chemotherapy course.
Similar content being viewed by others
References
Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 1986;314:1600–6.
Bacci G, Longhi A, Fagioli F, Briccoli A, Versari M, Picci P. Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy. Eur J Cancer. 2005;41:2836–45.
Fletcher BD. Response of osteosarcoma and Ewing sarcoma to chemotherapy: imaging evaluation. AJR Am J Roentgenol. 1991;157:825–33.
Meyers PA, Heller G, Healey J, Huvos A, Lane J, Marcove R, et al. Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol. 1992;10:5–15.
Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20:776–90.
Salzer-Kuntschik M, Brand G, Delling G. Determination of the degree of morphological regression following chemotherapy in malignant bone tumors. Pathologe. 1983;4:135–41.
Raymond AK, Chawla SP, Carrasco CH, Ayala AG, Fanning CV, Grice B, et al. Osteosarcoma chemotherapy effect: a prognostic factor. Semin Diagn Pathol. 1987;4:212–36.
Swisher SG, Maish M, Erasmus JJ, Correa AM, Ajani JA, Bresalier R, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg. 2004;78:1152–60.
Weber WA, Petersen V, Schmidt B, Tyndale-Hines L, Link T, Peschel C, et al. Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol. 2003;21:2651–7.
Brun E, Kjellen E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck. 2002;24:127–35.
Schelling M, Avril N, Nahrig J, Kuhn W, Romer W, Sattler D, et al. Positron emission tomography using [(18)F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol. 2000;18:1689–95.
Ye Z, Zhu J, Tian M, Zhang H, Zhan H, Zhao C, et al. Response of osteogenic sarcoma to neoadjuvant therapy: evaluated by 18F-FDG-PET. Ann Nucl Med. 2008;22:475–80.
Hawkins DS, Rajendran JG, Conrad 3rd EU, Bruckner JD, Eary JF. Evaluation of chemotherapy response in pediatric bone sarcomas by [F-18]-fluorodeoxy-D-glucose positron emission tomography. Cancer. 2002;94:3277–84.
Schulte M, Brecht-Krauss D, Werner M, Hartwig E, Sarkar MR, Keppler P, et al. Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG PET. J Nucl Med. 1999;40:1637–43.
Benz MR, Allen-Auerbach MS, Eilber FC, Chen HJ, Dry S, Phelps ME, et al. Combined assessment of metabolic and volumetric changes for assessment of tumor response in patients with soft-tissue sarcomas. J Nucl Med. 2008;49:1579–84.
Picci P, Bacci G, Campanacci M, Gasparini M, Pilotti S, Cerasoli S, et al. Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy. Regional mapping of viable and nonviable tumor. Cancer. 1985;56:1515–21.
Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M. Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol. 1994;12:2699–705.
Biehl KJ, Kong FM, Dehdashti F, Jin JY, Mutic S, El Naqa I, et al. 18F-FDG PET definition of gross tumor volume for radiotherapy of non-small cell lung cancer: is a single standardized uptake value threshold approach appropriate? J Nucl Med. 2006;47:1808–12.
Larson SM, Erdi Y, Akhurst T, Mazumdar M, Macapinlac HA, Finn RD, et al. Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging. The visual response score and the change in total lesion glycolysis. Clin Positron Imaging. 1999;2:159–71.
Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, et al. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med. 2001;42:1551–5.
Lee JD, Yang WI, Park YN, Kim KS, Choi JS, Yun M, et al. Different glucose uptake and glycolytic mechanisms between hepatocellular carcinoma and intrahepatic mass-forming cholangiocarcinoma with increased 18F-FDG uptake. J Nucl Med. 2005;46:1753–9.
Tian M, Zhang H, Nakasone Y, Mogi K, Endo K. Expression of Glut-1 and Glut-3 in untreated oral squamous cell carcinoma compared with FDG accumulation in a PET study. Eur J Nucl Med Mol Imaging. 2004;31:5–12.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti III A. Bone. In: Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti III A, editors. AJCC cancer staging manual. 7th ed. New York: Springer; 2010. p. 281–90.
Costelloe CM, Macapinlac HA, Madewell JE, Fitzgerald NE, Mawlawi OR, Rohren EM, et al. 18F-FDG PET/CT as an indicator of progression-free and overall survival in osteosarcoma. J Nucl Med. 2009;50:340–7.
Cheon GJ, Kim MS, Lee JA, Lee S-Y, Cho WH, Song WS, et al. Prediction model of chemotherapy response in osteosarcoma by 18F-FDG PET and MRI. J Nucl Med. 2009;50:1435–40.
Denecke T, Hundsdörfer P, Misch D, Steffen I, Schönberger S, Furth C, et al. Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters. Eur J Nucl Med Mol Imaging. 2010;37:1842–53.
Hawkins DS, Conrad 3rd EU, Butrynski JE, Schuetze SM, Eary JF. [F-18]-Fluorodeoxy-D-glucose-positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults. Cancer. 2009;115:3519–25.
Hayashida Y, Yakushiji T, Awai K, Katahira K, Nakayama Y, Shimomura O, et al. Monitoring therapeutic responses of primary bone tumors by diffusion-weighted image: initial results. Eur Radiol. 2006;16:2637–43.
Acknowledgment
This work was financially supported by the National Cancer Center, Korea (grant nos. 0710090 and 0710072–2, in part).
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Seok-ki Kim and Byung-Kiu Park contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Table S1
Glut1 and Glut3 expression in the tumour tissues before and after chemotherapy (DOC 66 kb)
Rights and permissions
About this article
Cite this article
Im, H.J., Kim, T.S., Park, SY. et al. Prediction of tumour necrosis fractions using metabolic and volumetric 18F-FDG PET/CT indices, after one course and at the completion of neoadjuvant chemotherapy, in children and young adults with osteosarcoma. Eur J Nucl Med Mol Imaging 39, 39–49 (2012). https://doi.org/10.1007/s00259-011-1936-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-011-1936-4