Advertisement

Advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with oral squamous cell carcinoma

  • Jun Sato
  • Yoshimasa Kitagawa
  • Yutaka Yamazaki
  • Hironobu Hata
  • Takuya Asaka
  • Masaaki Miyakoshi
  • Shozo Okamoto
  • Tohru Shiga
  • Masanobu Shindoh
  • Yuji Kuge
  • Nagara Tamaki
Original Article

Abstract

Purpose

Hypoxia, a prognostic factor in many types of cancer, can be detected by 18F-fluoromisonidazole (FMISO) positron emission tomography (PET). It is unclear whether hypoxia reflects the response to chemotherapy in patients with oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET with histological response to preoperative chemotherapy were therefore assessed in patients with OSCC.

Methods

This study enrolled 22 patients with OSCC undergoing preoperative chemotherapy. The T-stages were T2 in 6 patients, T3 in 3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5. Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the maximum standardized uptake value (SUVmax) of FDG- and FMISO-PET and tumor-muscle ratio (TMR) of FMISO-PET were measured. The threshold for the hypoxic volume based on TMR was set at 1.25. The histological response to preoperative chemotherapy was evaluated using operative materials.

Results

FMISO-PET and FDG-PET detected uptake by primary OSCCs in 15 (68 %) and 21 (95 %) patients, respectively, and median SUVmaxs of FMISO- and FDG-PET in the primary site were 2.0 (range, 1.3–3.5) and 16.0 (range, 1.0–32.2), respectively. The median of FMISO TMR was 1.5 (range, 0.99–2.96). There were five cases whose FMISO TMR was less than 1.25. Histological evaluation showed good response to preoperative chemotherapy in 7 patients (32 %) and poor response in 15 (68 %). Good response was significantly more prevalent in patients with negative than positive FMISO uptake (P < 0.001) and without the hypoxic area evaluated by FMISO-PET TMR (P = 0.04), whereas FDG uptake was not significantly correlated with response to chemotherapy response. Multivariate logistic regression analysis showed that FMISO uptake was an independent significant predictor of response to preoperative chemotherapy (P = 0.03, odds ratio = 0.06, 95 % confidence interval = 0.004–0.759).

Conclusions

An advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with OSCC was observed.

Keywords

Hypoxia FMISO-PET FDG-PET Preoperative chemotherapy HIF-1α Oral squamous cell carcinoma 

Notes

Acknowledgments

This study was partially supported by a Grant-in-Aid for Scientific Research (2010–2011: 22592203).

Conflict of interest

None of the authors of this manuscript has any financial relationship with any organization, or any conflict of interest, regarding this study.

Supplementary material

259_2014_2810_MOESM1_ESM.ppt (47 kb)
Supplementary figure 1 TMR of FMISO-PET or SUV max of FDG-PET and response to chemotherapy in nine patients who received PET examination before chemotherapy. White and black circles indicate patients having tumors without (n = 2) and with (n = 7) FMISO uptake, respectively. Dotted circles indicate the seven patients who showed good histological response to preoperative chemotherapy (PPT 47 kb)
259_2014_2810_MOESM2_ESM.ppt (50 kb)
Supplementary figure 2 TMR of FMISO-PET or SUV max of FDG-PET and response to chemotherapy in 13 patients who received PET examination after initiating chemotherapy. White and black circles indicate patients having tumors without (n = 5) and with (n = 8) FMISO uptake, respectively. Dotted circles indicate the seven patients who showed good histological response to preoperative chemotherapy (PPT 50 kb)

References

  1. 1.
    Wang W, Lee NY, Georgi JC, Narayanan M, Guillem J, Schöder H, et al. Pharmacokinetic analysis of hypoxia 18F-fluoromisonidazole dynamic PET in head and neck cancer. J Nucl Med. 2010;51:37–45.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Janssen HL, Haustermans KM, Balm AJ, Begg AC. Hypoxia in head and neck cancer: How much, how important? Head Neck. 2005;27:622–38.PubMedCrossRefGoogle Scholar
  3. 3.
    Roh JL, Cho KJ, Kwon GY, Ryu CH, Chang HW, Choi SH, et al. The prognostic value of hypoxia markers in T2-staged oral tongue cancer. Oral Oncol. 2009;45:63–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Yamane T, Kikuchi M, Shinohara S, Senda M. Reduction of [18F]-Fluoromisonidazole uptake after neoadjuvant chemotherapy for head and neck squamous cell carcinoma. Mol Imaging Biol. 2011;13:227–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Miyagaki H, Yamasaki M, Miyata H, Takahashi T, Kurokawa Y, Nakajima K, et al. Overexpression of PETK1 predicts resistance to chemotherapy in patients with oesophageal squamous cell carcinoma. Br J Cancer. 2012;106:947–54.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Kong CB, Byun BH, Lim I, Choi CW, Lim SM, Song WS, et al. 18F-FDG PET SUVmax as an indicator of histopathologic response after neoadjuvant chemotherapy in extremity osteosarcoma. Eur J Nucl Mol Imaging. 2013;40:728–36.CrossRefGoogle Scholar
  7. 7.
    Miyawaki A, Ikeda R, Hijioka H, Ishida T, Ushiyama N, Nozoe E, et al. SUVmax of FDG-PET correlates with the effect of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma. Oncol Rep. 2010;23:1205–12.PubMedCrossRefGoogle Scholar
  8. 8.
    Kitagawa Y, Sadato N, Azuma H, Ogasawara T, Yoshida M, Ishii Y, et al. FDG PET to evaluate combination intra-arterial chemotherapy and radiotherapy of head and neck neoplasms. J Nucl Med. 1999;40:1132–7.PubMedGoogle Scholar
  9. 9.
    Swisher SG, Erasmus J, Maish M, Correa AM, Macapinlac H, Ajani JA, et al. 2-fluoro-2-deoxy-d-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma. Cancer. 2004;101:1776–85.PubMedCrossRefGoogle Scholar
  10. 10.
    Lowe VJ, Dunphy FR, Varvares M, Kim H, Wittry M, Dunphy CH, et al. Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18] fluorodeoxyglucose positron emission tomography. Head Neck. 1997;19:666–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Kitagawa Y, Sano K, Nishizawa S, Nakamura M, Ogasawara T, Sadato N, et al. FDG PET for prediction of tumor aggressiveness and response to intra-arterial chemotherapy and radiotherapy in head and neck cancer. Eur J Nucl Med. 2003;30:63–71.CrossRefGoogle Scholar
  12. 12.
    Han MW, Lee HJ, Cho KJ, Kim JS, Roh JL, Choi SH, et al. Pole of FDG-pet as a biological marker for predicting the hypoxic status of tongue cancer. Head Neck. 2012;34:1395–402.PubMedCrossRefGoogle Scholar
  13. 13.
    Dierckx RA, Van de Wiele C. FDG uptake, a surrogate of tumour hypoxia? Eur J Nucl Med Imaging. 2008;35:1544–9.CrossRefGoogle Scholar
  14. 14.
    Toma-Dasu I, Dasu A, Brahme A. Quantifying tumour hypoxia by PET imaging- a theoretical analysis. Adv Exp Med Biol. 2009;645:267–72.PubMedCrossRefGoogle Scholar
  15. 15.
    Busk M, Horsman MR, Jakobsen S, Bussink J, van der Kogel A, Overgaard J. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. Eur J Nucl Med Mol Imaging. 2008;35:2294–303.PubMedCrossRefGoogle Scholar
  16. 16.
    Eschmann SM, Paulsen F. Bedes ing with 18F-misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer. Radiother Oncol. 2007;83:406–10.PubMedCrossRefGoogle Scholar
  17. 17.
    Koh WJ, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, et al. Imaging of tumor hypoxia in human tumors with [F-18] fluoromisonidazole. Int J Radiat Oncol Biol Phys. 1992;22:199–212.PubMedCrossRefGoogle Scholar
  18. 18.
    Rasey JS, Koh WJ, Fvans ML, Peterson LM, Lewellen TK, Michael Graham MM, et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [F-18] fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys. 1996;36:417–28.PubMedCrossRefGoogle Scholar
  19. 19.
    Rajendran JG, Wilson DC, Conrad EU, Peterson LK, Bruckner JD, Rasey JS, et al. [18F]FMISO and [18F] FDG PET imaging in soft tissue sarcoma: correlation of hypoxia, metabolism and VEGF expression. Eur J Nucl Med. 2003;30:695–704.CrossRefGoogle Scholar
  20. 20.
    Jansen JFA, Schöder H, Lee NY, Wang Y, Pfister DG, Fury MG, et al. Noninvasive assessment of tumor microenviroment using dynamic contrast-enhanced magnetic resonance imaging and 18F-fluoromisonidazole positron emission tomography imaging in neck nodal metastases. Int J Radiat Oncol Biol Phys. 2010;77:1403–10.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Lee ST, Scott AM. Hypoxia positron emission tomography imaging with 18-fluoromisonidazole. Semin Nucl Med. 2007;37:451–61.PubMedCrossRefGoogle Scholar
  22. 22.
    Okamoto S, Shiga T, Yasuda K, Ito YM, Magota K, Kasai K, et al. High reproducibility of tumor hypoxia evaluated by 18 F-Fluoromisonidazole PET for head and neck cancer. J Nucl Med. 2013;54:201–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Sato J, Kitagawa Y, Yamazaki Y, Hata H, Okamoto S, Shiga T, et al. FMISO-PET uptake is correlated with HIF-1α expression in oral squamous cell carcinoma. J Nucl Med. 2013;54:1060–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Harada H, Inoue M, Itasaka S, Hirota K, Morinibu A. Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels. Nat Commun. 2012;3:783–92.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Nordsmark M, Bentzen S, Rudat V, Brizel D, Lartigau E, Stadler P, et al. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol. 2005;77:18–24.PubMedCrossRefGoogle Scholar
  26. 26.
    Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3:721–32.PubMedCrossRefGoogle Scholar
  27. 27.
    Lin PY, Yu CH, Wang JT, et al. Expression of hypoxia-inducible factor-1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan. J Oral Pathol Med. 2008;37:18–25.PubMedCrossRefGoogle Scholar
  28. 28.
    Sasabe E, Zhou X, Li D, Oku N, Yamamoto T, Osaki T. The involvement of hypoxia-inducible factor-αin the susceptibility to γ-rays and chemotherapeutic drugs of oral squamous cell carcinoma cells. Int J Cancer. 2006;120:268–77.CrossRefGoogle Scholar
  29. 29.
    Sasabe E, Tatemoto Y, Li D, Yamamoto T, Osaki T. Mechanism of HIF-1α-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells. Cancer Sci. 2005;96:394–402.PubMedCrossRefGoogle Scholar
  30. 30.
    van den Broek GB, Wildeman M, Rasch CRN, Armstrong N, Schuuring E, Begg AC, et al. Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation. Int J Cancer. 2009;124:2643–50.PubMedCrossRefGoogle Scholar
  31. 31.
    Barnes L, Eveson J, Reichart P, Barnes L, Sidransky D. World Health Organization Classification of Tumors, Pathology and Genetics of Tumors of the Head and Neck. International Agency for Research on Cancer. Lyon: IARC Press; 2005.Google Scholar
  32. 32.
    Sobin LH, Wittenkind CH. TNM Classification of Malignant Tumors. 5th ed. New York: John Wiley & Sons, Inc; 1997. p. 17–42.Google Scholar
  33. 33.
    Yamamoto E, Kohama G, Sunakawa H, Iwai M, Hiratsuka H. Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity. Cancer. 1983;51:2175–80.PubMedCrossRefGoogle Scholar
  34. 34.
    Japan Society for Head and Neck Cancer. General rules for clinical studies on head and neck cancer. 5th ed. Tokyo: KANEHARS & Co., LTD; 2012. p. 68.Google Scholar
  35. 35.
    Fillies T, Werkmeister R, van Diest P, Brandt B, Joos U, Buerger H. HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinoma of the oral floor. BMC Cancer. 2005;5:84–91.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Yoshida S, Ito D, Nagumo T, Shirota T, Hatori M, Shintani S. Hypoxia induces resistance to 5-fluorouracil in oral cancer cells via G1 phase cell cycle arrest. Oral Oncol. 2009;45:109–15.CrossRefGoogle Scholar
  37. 37.
    Song X, Liu X, Chi W, Wei L, Wang X, Yu J. Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1 alpha gene. Cancer Chemother Pharmacol. 2006;58:776–84.PubMedCrossRefGoogle Scholar
  38. 38.
    Schliephake H. Prognostic relevance of molecular markers of oral cancer-A review. Int J Oral Maxillofac Surg. 2003;32:233–45.PubMedCrossRefGoogle Scholar
  39. 39.
    Nemeth Z, Velich N, Bogdan S, Ujpál M, Szabó G, Suba ZS. The prognostic role of clinical, morphological and molecular markers in oral squamous cell tumors. Neoplasma. 2005;52:95–102.PubMedGoogle Scholar
  40. 40.
    Olive PL, Durand RE. During and radiation resistance in spheroids: cell contact and kinetics. Cancer Metastasis Rev. 1994;13:121–38.PubMedCrossRefGoogle Scholar
  41. 41.
    Teicher BA. Hypoxia and drug resistance. Cancer Metastasis Rev. 1997;13:139–68.CrossRefGoogle Scholar
  42. 42.
    Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto SP, Colgan SP. Hypoxia-inducible factor-1-dependdent regulation of the multidrug resistance (MDR1) gene. Cancer Res. 2002;62:3387–94.PubMedGoogle Scholar
  43. 43.
    Birner P, Schindl M, Obermair A, Breitenecker G, Oberhuber G. Expression of hypoxia-inducible factor 1α in epitherial ovarian tumors: its impact on prognosis and on response to chemoptherapy. Clin Cancer Res. 2001;7:1661–8.PubMedGoogle Scholar
  44. 44.
    Yamazaki M, Miyata H, Fujiwara Y, Takiguchi S, Nakajima K, Nishida T, et al. p53 genotype predicts response to chemotherapy in patients with squamous cell carcinoma of the wsophagus. Ann Surg Oncol. 2010;17:634–42.CrossRefGoogle Scholar
  45. 45.
    Moreno-Galindo C, Hermsen M, Graćia-Pedreo JM, Fresno MF, Suá C, Rodrigo JP. P27 and BCL2 expression predicts response to chemotherapy in head and neck squamous cell carcinomas. Oral Oncol. 2014;50:128–34.PubMedCrossRefGoogle Scholar
  46. 46.
    Hawkins DS, Rajendran JG, Conrad 3rd EU, Bruckner JD. Evaluation of chemotherapy response in pediatric bone sarcomas by [F-18]-fluorodeoxy-D-glucose positron emission tomography. Cancer. 2002;94:3277–84.Google Scholar
  47. 47.
    Lee NY, Mechalakos JG, Nehmeh S, Zhixiong Lin Z, Squire OD, Cai S, et al. Reproducibility of intratumor distribution of (18) F-fluoromisonidazole in head and neck cancer. Int J Radiat Oncol Biol Phys. 2008;70:235–42.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    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 on a PET study. Eur J Nucl Med Mol Imaging. 2004;31:5–12.PubMedCrossRefGoogle Scholar
  49. 49.
    Ak I, Stokkel MP, Pauwels EK. Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose in oncology. Part II. The clinical value in detecting and staging primary tumours. J Cancer Res Clin Oncol. 2000;126:560–74.PubMedCrossRefGoogle Scholar
  50. 50.
    Kalz S, Kalzova N, Liao SY, Lwman N, Stanbridge EJ. Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: a one transcription factor (HIF-1) show? Biochem Biophys Acta. 2009;1795:162–72.Google Scholar
  51. 51.
    Silva P, Slevin NJ, Sloan P, Valentine H, Cresswell J, Ryder D, et al. Prognostic significance of tumor hypoxia inducible factor-1alpha expression for outcome after radiotherapy in oropharyngeal cancer. Int J Radiat Oncol Biol Phys. 2008;72:1551–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Zimny M, Gagel B, DiMartino E, Hamacher K, Coenen H, Westhofen M, et al. FDG-a marker of tumor hypoxia? A comparison with [(18)Fluoromisonidazole and pO2-polarography in metastatic head and neck cancer. Eur J Nucl Med Mol Imaging. 2006;33:1426–31.PubMedCrossRefGoogle Scholar
  53. 53.
    Rajendran JG, Mankoff DA, O’Sullivan F, Peterson LM, Schwartz DL, Conrad EU, et al. Hypoxia and glucose metabolism in malignant tumor: evaluation by [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res. 2004;10:2245–52.PubMedCrossRefGoogle Scholar
  54. 54.
    Shimosato Y, Oboshi S, Baba K. Histological evaluation of effects of radiotherapy and chemotherapy for carcinoma. J Clin Oncol. 1971;1:19–35.Google Scholar
  55. 55.
    Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. New Engl J Med. 2010;363:24–35.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jun Sato
    • 1
  • Yoshimasa Kitagawa
    • 1
  • Yutaka Yamazaki
    • 1
  • Hironobu Hata
    • 1
  • Takuya Asaka
    • 1
  • Masaaki Miyakoshi
    • 1
  • Shozo Okamoto
    • 2
  • Tohru Shiga
    • 2
  • Masanobu Shindoh
    • 3
  • Yuji Kuge
    • 4
  • Nagara Tamaki
    • 2
  1. 1.Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Graduate School of Dental MedicineHokkaido UniversitySapporoJapan
  2. 2.Department of Nuclear Medicine, Graduate School of MedicineHokkaido UniversitySapporoJapan
  3. 3.Department of Oral Pathology & BiologyHokkaido University Graduate School of Dental MedicineSapporoJapan
  4. 4.Central Institute of Isotope ScienceHokkaido UniversitySapporoJapan

Personalised recommendations