18F-FDG PET SUVmax as an indicator of histopathologic response after neoadjuvant chemotherapy in extremity osteosarcoma

  • Chang-Bae Kong
  • Byung Hyun Byun
  • Ilhan Lim
  • Chang Woon Choi
  • Sang Moo LimEmail author
  • Won Seok Song
  • Wan Hyeong Cho
  • Dae-Geun Jeon
  • Jae-Soo Koh
  • Ji Young Yoo
  • Soo-Yong Lee
Original Article



This study evaluated the usefulness of the maximum standardized uptake value (SUVmax) as a measure of histologic response to neoadjuvant chemotherapy in patients with extremity osteosarcoma. The correlation between [18 F]FDG PET SUVmax values and histologic response to preoperative chemotherapy was also assessed prospectively using PET/MRI.


A total of 26 consecutive patients with high-grade osteosarcoma were prospectively enrolled. All patients underwent parallel PET and MRI scans before and after neoadjuvant chemotherapy. Using the PET and MRI images and pathologic mapping, we assessed the percentage necrosis by histology at the highest metabolic activity point in the tumors. This was defined as the minimum histologic response. The predictive values of SUVmax before (SUV1) and after (SUV2) chemotherapy and the SUV change ratio were determined. Correlations were also investigated among SUV2, minimum histologic response and histologic response.


Histologically, 13 patients were classified as good responders and 13 as poor responders. Patients with an SUV2 of >5 showed a poor histologic response. A significant correlation was found between SUV2 and histologic response (Spearman’s rho −0.642; P < 0.001), and SUV2 and histologic response were both found to be significantly correlated with minimum histologic response (Spearman’s rho −0.515 and 0.911; P = 0.007 and P < 0.001, respectively).


A SUVmax of more than 5 after neoadjuvant chemotherapy identified the majority of histologic nonresponders (sensitivity 61.3 %, PPV 88.9 %). Tumor necrosis at the point of maximum metabolic activity was found to be significantly correlated with the histologic response of entire resected specimen.


Osteosarcoma FDG PET SUVmax Histologic response 



This study was supported by a grant of the RTR (Radiological Translational Research program), Korea Institute of Radiological & Medical Sciences (50453–2011).

Conflicts of interest



  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    Kim MS, Lee SY, Lee TR, Cho WH, Song WS, Koh JS, et al. Prognostic nomogram for predicting the 5-year probability of developing metastasis after neo-adjuvant chemotherapy and definitive surgery for AJCC stage II extremity osteosarcoma. Ann Oncol. 2009;20:955–60.PubMedCrossRefGoogle Scholar
  3. 3.
    Rosen G, Marcove RC, Caparros B, Nirenberg A, Kosloff C, Huvos AG. Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery. Cancer. 1979;43:2163–77.PubMedCrossRefGoogle Scholar
  4. 4.
    Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Cheon GJ, Kim MS, Lee JA, Lee SY, 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.PubMedCrossRefGoogle Scholar
  6. 6.
    Hoh CK, Hawkins RA, Glaspy JA, Dahlbom M, Tse NY, Hoffman EJ, et al. Cancer detection with whole-body PET using 2-[18F]fluoro-2-deoxy-D-glucose. J Comput Assist Tomogr. 1993;17:582–9.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 9.
    Franzius C, Bielack S, Flege S, Sciuk J, Jurgens H, Schober O. Prognostic significance of (18)F-FDG and (99m)Tc-methylene diphosphonate uptake in primary osteosarcoma. J Nucl Med. 2002;43:1012–7.PubMedGoogle Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    Bajpai J, Kumar R, Sreenivas V, Chand Sharma M, Khan SA, Rastogi S, et al. Prediction of chemotherapy response by PET-CT in osteosarcoma: correlation with histologic necrosis. J Pediatr Hematol Oncol. 2011;33:e271–8.PubMedGoogle Scholar
  12. 12.
    Benz MR, Evilevitch V, Allen-Auerbach MS, Eilber FC, Phelps ME, Czernin J, et al. Treatment monitoring by 18F-FDG PET/CT in patients with sarcomas: interobserver variability of quantitative parameters in treatment-induced changes in histopathologically responding and nonresponding tumors. J Nucl Med. 2008;49:1038–46.PubMedCrossRefGoogle Scholar
  13. 13.
    Costelloe CM, Raymond AK, Fitzgerald NE, Mawlawi OR, Nunez RF, Madewell JE, et al. Tumor necrosis in osteosarcoma: inclusion of the point of greatest metabolic activity from F-18 FDG PET/CT in the histopathologic analysis. Skeletal Radiol. 2010;39:131–40.PubMedCrossRefGoogle Scholar
  14. 14.
    Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, et al. Tumor necrosis rate adjusted by tumor volume change is a better predictor of survival of localized osteosarcoma patients. Ann Surg Oncol. 2008;15:906–14.PubMedCrossRefGoogle Scholar
  15. 15.
    Rosen G, Marcove RC, Huvos AG, Caparros BI, Lane JM, Nirenberg A, et al. Primary osteogenic sarcoma: eight-year experience with adjuvant chemotherapy. J Cancer Res Clin Oncol. 1983;106 Suppl:55–67.PubMedCrossRefGoogle Scholar
  16. 16.
    Coffin CM, Lowichik A, Zhou H. Treatment effects in pediatric soft tissue and bone tumors: practical considerations for the pathologist. Am J Clin Pathol. 2005;123:75–90.PubMedCrossRefGoogle Scholar
  17. 17.
    Göbel V, Jürgens H, Etspüler G, Kemperdick H, Jungblut RM, Stienen U, et al. Prognostic significance of tumor volume in localized Ewing’s sarcoma of bone in children and adolescents. J Cancer Res Clin Oncol. 1987;113:187–91.Google Scholar
  18. 18.
    Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, et al. Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol. 1996;14:848–58.PubMedGoogle Scholar
  19. 19.
    Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, et al. An examination of the efficacy of the 8 cm maximal tumor diameter cutoff for the subdivision of AJCC stage II osteosarcoma patients. J Surg Oncol. 2008;98:427–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Franzius C, Sciuk J, Brinkschmidt C, Jurgens H, Schober O. Evaluation of chemotherapy response in primary bone tumors with F-18 FDG positron emission tomography compared with histologically assessed tumor necrosis. Clin Nucl Med. 2000;25:874–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Huang TL, Liu RS, Chen TH, Chen WY, Hsu HC, Hsu YC. Comparison between F-18-FDG positron emission tomography and histology for the assessment of tumor necrosis rates in primary osteosarcoma. J Chin Med Assoc. 2006;69:372–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50 Suppl 1:122S–50.PubMedCrossRefGoogle Scholar
  23. 23.
    Velasquez LM, Boellaard R, Kollia G, Hayes W, Hoekstra OS, Lammertsma AA, et al. Repeatability of 18F-FDG PET in a multicenter phase I study of patients with advanced gastrointestinal malignancies. J Nucl Med. 2009;50:1646–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Vanderhoek M, Perlman SB, Jeraj R. Impact of the definition of peak standardized uptake value on quantification of treatment response. J Nucl Med. 2012;53:4–11.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    Martoni AA, Zamagni C, Quercia S, Rosati M, Cacciari N, Bernardi A, et al. Early (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography may identify a subset of patients with estrogen receptor-positive breast cancer who will not respond optimally to preoperative chemotherapy. Cancer. 2010;116:805–13.PubMedCrossRefGoogle Scholar
  27. 27.
    Kumar A, Kumar R, Seenu V, Gupta SD, Chawla M, Malhotra A, et al. The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Eur Radiol. 2009;19:1347–57.PubMedCrossRefGoogle Scholar
  28. 28.
    Lee HY, Lee HJ, Kim YT, Kang CH, Jang BG, Chung DH, et al. Value of combined interpretation of computed tomography response and positron emission tomography response for prediction of prognosis after neoadjuvant chemotherapy in non-small cell lung cancer. J Thorac Oncol. 2010;5:497–503.PubMedCrossRefGoogle Scholar
  29. 29.
    Guerra L, Niespolo R, Di Pisa G, Ippolito D, De Ponti E, Terrevazzi S, et al. Change in glucose metabolism measured by 18F-FDG PET/CT as a predictor of histopathologic response to neoadjuvant treatment in rectal cancer. Abdom Imaging. 2011;36:38–45.PubMedCrossRefGoogle Scholar
  30. 30.
    Chung HW, Lee EJ, Cho YH, Yoon SY, So Y, Kim SY, et al. High FDG uptake in PET/CT predicts worse prognosis in patients with metastatic gastric adenocarcinoma. J Cancer Res Clin Oncol. 2010;136:1929–35.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedCrossRefGoogle Scholar
  32. 32.
    Im HJ, Kim TS, Park SY, Min HS, Kim JH, Kang HG, 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. 2012;39:39–49.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Chang-Bae Kong
    • 1
  • Byung Hyun Byun
    • 2
  • Ilhan Lim
    • 2
  • Chang Woon Choi
    • 2
  • Sang Moo Lim
    • 2
    Email author
  • Won Seok Song
    • 1
  • Wan Hyeong Cho
    • 1
  • Dae-Geun Jeon
    • 1
  • Jae-Soo Koh
    • 3
  • Ji Young Yoo
    • 4
  • Soo-Yong Lee
    • 1
  1. 1.Department of Orthopedic SurgeryKorea Cancer Center HospitalSeoulSouth Korea
  2. 2.Department of Nuclear MedicineKorea Cancer Center HospitalSeoulSouth Korea
  3. 3.Department of PathologyKorea Cancer Center HospitalSeoulSouth Korea
  4. 4.Department of RadiologyKorea Cancer Center HospitalSeoulSouth Korea

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