Skip to main content

Advertisement

SpringerLink
Log in

Early FDG PET response assessment of preoperative radiochemotherapy in locally advanced rectal cancer: correlation with long-term outcome

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of the present study is to prospectively evaluate the prognostic value of previously defined [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) criteria of early metabolic response in patients with locally advanced rectal cancer (LARC) after long-term follow-up.

Methods

Forty-two patients with poor prognosis LARC underwent three biweekly courses of chemotherapy with oxaliplatin, raltitrexed and 5-fluorouracil modulated by levofolinic acid during pelvic radiotherapy. FDG PET studies were performed before and 12 days after the beginning of the chemoradiotherapy (CRT) treatment. Total mesorectal excision (TME) was carried out 8 weeks after completion of CRT. A previously identified cutoff value of ≥52 % reduction of the baseline mean FDG standardized uptake value (SUVmean) was applied to differentiate metabolic responders from non-responders and correlated to tumour regression grade (TRG) and survival.

Results

Twenty-two metabolic responders showed complete (TRG1) or subtotal tumour regression (TRG2) and demonstrated a statistically significantly higher 5-year relapse-free survival (RFS) compared with the 20 non-responders (86 vs 55 %, p = .014) who showed TRG3 and TRG4 pathologic responses. A multivariate analysis demonstrated that early ∆SUVmean was the only pre-surgical parameter correlated to the likelihood of recurrence (p = .05).

Conclusion

This study is the first prospective long-term evaluation demonstrating that FDG PET is not only an early predictor of pathologic response but is also a valuable prognostic tool. Our results indicate the potential of FDG PET for optimizing multidisciplinary management of patients with LARC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264:1444–50.

    Article  Google Scholar 

  2. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–40.

    Article  PubMed  CAS  Google Scholar 

  3. Avallone A, Delrio P, Lastoria S, Comella P. Chemo-radiotherapy in locally advanced rectal cancer: what is the optimal strategy? Eur J Cancer Suppl 2008;6:70–3.

    Article  Google Scholar 

  4. Gunderson LL, Sargent DJ, Tepper JE, Wolmark N, O’Connell MJ, Begovic M, et al. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 2004;22:1785–96.

    Article  PubMed  Google Scholar 

  5. Bujko K, Glynne-Jones R, Bujko M. Does adjuvant fluoropyrimidine-based chemotherapy provide a benefit for patients with resected rectal cancer who have already received neoadjuvant radiochemotherapy? A systematic review of randomised trials. Ann Oncol 2010;21:1743–50.

    Article  PubMed  CAS  Google Scholar 

  6. Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005;23:8688–96.

    Article  PubMed  Google Scholar 

  7. Vecchio FM, Valentini V, Minsky BD, Padula GD, Venkatraman ES, Balducci M, et al. The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 2005;62:752–60.

    Article  PubMed  Google Scholar 

  8. Borschitz T, Wachtlin D, Möhler M, Schmidberger H, Junginger T. Neoadjuvant chemoradiation and local excision for T2-3 rectal cancer. Ann Surg Oncol 2008;15:712–20.

    Article  PubMed  Google Scholar 

  9. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro Jr U, Silva e Sousa Jr AH, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 2004;240:711–7, discussion 717-8.

    PubMed  Google Scholar 

  10. Lezoche G, Baldarelli M, Guerrieri M, Paganini AM, De Sanctis A, Bartolacci S, et al. A prospective randomized study with a 5-year minimum follow-up evaluation of transanal endoscopic microsurgery versus laparoscopic total mesorectal excision after neoadjuvant therapy. Surg Endosc 2008;22:352–8.

    Article  PubMed  CAS  Google Scholar 

  11. MERCURY Study Group. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ 2006;333:779.

    Article  Google Scholar 

  12. Burton S, Brown G, Daniels IR, Norman AR, Mason B, Cunningham D, et al. MRI directed multidisciplinary team preoperative treatment strategy: the way to eliminate positive circumferential margins? Br J Cancer 2006;94:351–7.

    Article  PubMed  CAS  Google Scholar 

  13. Chen CC, Lee RC, Lin JK, Wang LW, Yang SH. How accurate is magnetic resonance imaging in restaging rectal cancer in patients receiving preoperative combined chemoradiotherapy? Dis Colon Rectum 2005;48:722–8.

    Article  PubMed  Google Scholar 

  14. Huh JW, Park YA, Jung EJ, Lee KY, Sohn SK. Accuracy of endorectal ultrasonography and computed tomography for restaging rectal cancer after preoperative chemoradiation. J Am Coll Surg 2008;207:7–12.

    Article  PubMed  Google Scholar 

  15. Kubota K. From tumor biology to clinical Pet: a review of positron emission tomography (PET) in oncology. Ann Nucl Med 2001;15:471–86.

    Article  PubMed  CAS  Google Scholar 

  16. Mac Manus MP, Hicks RJ, Matthews JP, McKenzie A, Rischin D, Salminen EK, et al. Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol 2003;21:1285–92.

    Article  PubMed  Google Scholar 

  17. Schelling M, Avril N, Nährig J, Kuhn W, Römer 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.

    PubMed  CAS  Google Scholar 

  18. Weber WA, Ott K, Becker K, Dittler HJ, Helmberger H, Avril NE, et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 2001;19:3058–65.

    PubMed  CAS  Google Scholar 

  19. Calvo FA, Domper M, Matute R, Martínez-Lázaro R, Arranz JA, Desco M, et al. 18F-FDG positron emission tomography staging and restaging in rectal cancer treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys 2004;58:528–35.

    Article  PubMed  Google Scholar 

  20. Cascini GL, Avallone A, Delrio P, Guida C, Tatangelo F, Marone P, et al. 18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. J Nucl Med 2006;47:1241–8.

    PubMed  CAS  Google Scholar 

  21. Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol 2006;24:4692–8.

    Article  PubMed  Google Scholar 

  22. Avallone A, Delrio P, Guida C, Tatangelo F, Petrillo A, Marone P, et al. Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I-II study. Br J Cancer 2006;94:1809–15.

    Article  PubMed  CAS  Google Scholar 

  23. Avallone A, Delrio P, Pecori B, Tatangelo F, Petrillo A, Scott N, et al. Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long-term outcome. Int J Radiat Oncol Biol Phys 2011;79:670–6.

    Article  PubMed  CAS  Google Scholar 

  24. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994;73:2680–6.

    Article  PubMed  CAS  Google Scholar 

  25. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.

    Article  Google Scholar 

  26. Cox DR. Regression models and life-tables. J R Stat Soc Series B Stat Methodol 1972;34:187–220.

    Google Scholar 

  27. Read TE, Andujar JE, Caushaj PF, Johnston DR, Dietz DW, Myerson RJ, et al. Neoadjuvant therapy for rectal cancer: histologic response of the primary tumor predicts nodal status. Dis Colon Rectum 2004;47:825–31.

    Article  PubMed  Google Scholar 

  28. Capirci C, Valentini V, Cionini L, De Paoli A, Rodel C, Glynne-Jones R, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys 2008;72:99–107.

    Article  PubMed  Google Scholar 

  29. Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010;11:835–44.

    Article  PubMed  Google Scholar 

  30. Fietkau R, Barten M, Klautke G, Klar E, Ludwig K, Thomas H, et al. Postoperative chemotherapy may not be necessary for patients with ypN0-category after neoadjuvant chemoradiotherapy of rectal cancer. Dis Colon Rectum 2006;49:1284–92.

    Article  PubMed  Google Scholar 

  31. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006;355:1114–23.

    Article  PubMed  CAS  Google Scholar 

  32. Bujko K, Michalski W, Kepka L, Nowacki MP, Nasierowska-Guttmejer A, Tokar P, et al. Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: an analysis of outcomes in a randomized trial. Int J Radiat Oncol Biol Phys 2007;67:369–77.

    Article  PubMed  Google Scholar 

  33. Gosens MJ, Klaassen RA, Tan-Go I, Rutten HJ, Martijn H, van den Brule AJ, et al. Circumferential margin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma. Clin Cancer Res 2007;13:6617–23.

    Article  PubMed  CAS  Google Scholar 

  34. Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM, et al. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg 2011;254:97–102.

    Article  PubMed  Google Scholar 

  35. de Geus-Oei LF, Vriens D, van Laarhoven HW, van der Graaf WT, Oyen WJ. Monitoring and predicting response to therapy with 18F-FDG PET in colorectal cancer: a systematic review. J Nucl Med 2009;50 Suppl 1:43S–54S.

    Article  PubMed  Google Scholar 

  36. Everaert H, Hoorens A, Vanhove C, Sermeus A, Ceulemans G, Engels B, et al. Prediction of response to neoadjuvant radiotherapy in patients with locally advanced rectal cancer by means of sequential 18FDG-PET. Int J Radiat Oncol Biol Phys 2011;80:91–6.

    Article  PubMed  Google Scholar 

  37. Janssen MH, Ollers MC, Riedl RG, van den Bogaard J, Buijsen J, van Stiphout RG, et al. Accurate prediction of pathological rectal tumor response after two weeks of preoperative radiochemotherapy using (18)F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging. Int J Radiat Oncol Biol Phys 2010;77:392–9.

    Article  PubMed  Google Scholar 

  38. Rosenberg R, Herrmann K, Gertler R, Künzli B, Essler M, Lordick F, et al. The predictive value of metabolic response to preoperative radiochemotherapy in locally advanced rectal cancer measured by PET/CT. Int J Colorectal Dis 2009;24:191–200.

    Article  PubMed  Google Scholar 

  39. Leibold T, Akhurst TJ, Chessin DB, Yeung HW, Macapinlac H, Shia J, et al. Evaluation of (18)F-FDG-PET for early detection of suboptimal response of rectal cancer to preoperative chemoradiotherapy: a prospective analysis. Ann Surg Oncol 2011;18:2783–9.

    Article  PubMed  Google Scholar 

  40. Capirci C, Rubello D, Chierichetti F, Crepaldi G, Fanti S, Mandoliti G, et al. Long-term prognostic value of 18F-FDG PET in patients with locally advanced rectal cancer previously treated with neoadjuvant radiochemotherapy. AJR Am J Roentgenol 2006;187:W202–8.

    Article  PubMed  Google Scholar 

  41. Martoni AA, Di Fabio F, Pinto C, Castellucci P, Pini S, Ceccarelli C, et al. Prospective study on the FDG-PET/CT predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer. Ann Oncol 2011;22:650–6.

    Article  PubMed  CAS  Google Scholar 

  42. Yeung JM, Kalff V, Hicks RJ, Drummond E, Link E, Taouk Y, et al. Metabolic response of rectal cancer assessed by 18-FDG PET following chemoradiotherapy is prognostic for patient outcome. Dis Colon Rectum 2011;54:518–25.

    Article  PubMed  CAS  Google Scholar 

  43. Ruby JA, Leibold T, Akhurst TJ, Shia J, Saltz LB, Mazumdar M, et al. FDG-PET assessment of rectal cancer response to neoadjuvant chemoradiotherapy is not associated with long-term prognosis: a prospective evaluation. Dis Colon Rectum 2012;55:378–86.

    Article  PubMed  Google Scholar 

  44. Ott K, Herrmann K, Lordick F, Wieder H, Weber WA, Becker K, et al. Early metabolic response evaluation by fluorine-18 fluorodeoxyglucose positron emission tomography allows in vivo testing of chemosensitivity in gastric cancer: long-term results of a prospective study. Clin Cancer Res 2008;14:2012–8.

    Article  PubMed  CAS  Google Scholar 

  45. Aloj L, Caracò C, Di Gennaro F, Squame E, Imbimbo S, Pecori B, et al. Predictive role of FDG PET-CT in monitoring locally advanced rectal cancer (LARC) during preoperative radiochemotherapy with an experimental bevacizumab schedule. Proceedings of the Annual Meeting of the Society of Nuclear Medicine, Miami Beach, 9–13 June 2012, abstract 569.

  46. Janssen MH, Ollers MC, van Stiphout RG, Buijsen J, van den Bogaard J, de Ruysscher D, et al. Evaluation of early metabolic responses in rectal cancer during combined radiochemotherapy or radiotherapy alone: sequential FDG-PET-CT findings. Radiother Oncol 2010;94:151–5.

    Article  PubMed  Google Scholar 

  47. Ghadimi BM, Grade M, Difilippantonio MJ, Varma S, Simon R, Montagna C, et al. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol 2005;23:1826–38.

    Article  PubMed  CAS  Google Scholar 

  48. Watanabe T, Komuro Y, Kiyomatsu T, Kanazawa T, Kazama Y, Tanaka J, et al. Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res 2006;66:3370–4.

    Article  PubMed  CAS  Google Scholar 

  49. Bui T, Thompson CB. Cancer’s sweet tooth. Cancer Cell 2006;9:419–20.

    Article  PubMed  CAS  Google Scholar 

  50. Kim JW, Dang CV. Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res 2006;66:8927–30.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Financial support for this work was provided by grants of the Italian Ministry of Health (Ricerca Corrente M3/13 and M2/20, INT “G. Pascale”; Ricerca Finalizzata RF-2009-1539464). The authors are grateful to Dr. Pasquale Comella for critical review of the statistical analysis and interpretation of the results. We thank Dr. Alessandra Trocino for providing excellent bibliographic service and assistance.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Via M. Semmola, 80131, Naples, Italy

    Antonio Avallone, Rossana Casaretti, Massimo Montano & Lucrezia Silvestro

  2. Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Via M. Semmola, 80131, Naples, Italy

    Luigi Aloj, Corradina Caracò, Francesca Di Gennaro & Secondo Lastoria

  3. Department of Surgical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Naples, Italy

    Paolo Delrio

  4. Department of Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Naples, Italy

    Biagio Pecori

  5. Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Naples, Italy

    Fabiana Tatangelo

  6. Department of Experimental Pharmacology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Naples, Italy

    Alfredo Budillon

  7. Department of Pathology, St. James University Hospital, Leeds, UK

    Nigel Scott

Authors
  1. Antonio Avallone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luigi Aloj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Corradina Caracò
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Delrio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Biagio Pecori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fabiana Tatangelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nigel Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rossana Casaretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Francesca Di Gennaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Massimo Montano
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lucrezia Silvestro
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alfredo Budillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Secondo Lastoria
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Antonio Avallone or Luigi Aloj.

Additional information

Antonio Avallone and Luigi Aloj are co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Avallone, A., Aloj, L., Caracò, C. et al. Early FDG PET response assessment of preoperative radiochemotherapy in locally advanced rectal cancer: correlation with long-term outcome. Eur J Nucl Med Mol Imaging 39, 1848–1857 (2012). https://doi.org/10.1007/s00259-012-2229-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-012-2229-2

Keywords

Search

Navigation