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18F-FDG PET/CT-based treatment response evaluation in locally advanced rectal cancer: a prospective validation of long-term outcomes

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Abstract

Purpose

To prospectively evaluate the usefulness of 18F-FDG PET/CT) imaging for predicting histopathological response and long-term clinical outcomes in locally advanced rectal cancer (LARC).

Methods

This prospective study included 38 patients with a confirmed diagnosis of LARC (cT3-4 or cN+) who underwent 18F-FDG PET/CT before and after neoadjuvant therapy (NAT). Total mesorectal excision was scheduled 6 weeks after NAT and was followed by an expert histopathological analysis of the surgical specimen. Baseline variables and previously identified maximum FDG standardized uptake value (SUVmax) cut-off values before NAT (SUVmaxPRE ≥6) and after NAT (SUVmaxPOST ≥2), and the absolute and percentage reductions from baseline SUVmax (∆SUVmax <4 and ∆SUVmax% <65 %, respectively) were applied to differentiate patients showing a metabolic tumour response from nonresponders. These features were correlated with tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS).

Results

Significantly higher 5-year DFS and OS were seen in 19 responders (TRG 3 or 4) than in 19 nonresponders (TRG 0–2; 94.4 vs. 48.8 %, p = 0.001; 94.7 vs. 63.2 %, p = 0.02, respectively). In multivariate analysis the only PET/CT SUVmax-based parameter significantly correlated with the likelihood of recurrence and survival was ∆SUV% <65 % (HR = 5.95, p = 0.02, for DFS; HR = 5.26, p = 0.04, for OS)

Conclusion

This prospective study proved that 18F-FDG PET/CT is a valuable imaging tool for assessing rectal cancer TRG and long-term prognosis, and could potentially serve as an intermediate endpoint in treatment optimization research and rectal cancer patient care.

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References

  1. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986;1:1479–82.

    Article  PubMed  CAS  Google Scholar 

  2. Smith N, Brown G. Preoperative staging of rectal cancer. Acta Oncol. 2008;47:20–31.

    Article  PubMed  Google Scholar 

  3. Nagtegaal ID, van Krieken JH. The role of pathologists in the quality control of diagnosis and treatment of rectal cancer – an overview. Eur J Cancer. 2002;38:964–72.

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12:575–82.

    Article  PubMed  Google Scholar 

  6. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Pudełko M, et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol. 2004;72:15–24.

    Article  PubMed  CAS  Google Scholar 

  7. Blomqvist L, Glimelius B. The “good”, the “bad”, and the “ugly” rectal cancers. Acta Oncol. 2008;47:5–8.

    Article  PubMed  Google Scholar 

  8. Shields AF. Positron emission tomography measurement of tumor metabolism and growth: its expanding role in oncology. Mol Imaging Biol. 2006;8:141–50.

    Article  PubMed  Google Scholar 

  9. Ichiya Y, Kuwabara Y, Otsuka M, Tahara T, Yoshikai T, Fukumura T, et al. Assessment of response to cancer therapy using fluorine-18 fluorodeoxyglucose and positron emission tomography. J Nucl Med. 1991;32:1655–60.

    PubMed  CAS  Google Scholar 

  10. Capirci C, Rampin L, Erba PA, Galeotti F, Crepaldi G, Banti E, et al. Sequential FDG-PET/CT reliably predicts response of locally advanced rectal cancer to neo-adjuvant chemo-radiation therapy. Eur J Nucl Med Mol Imaging. 2007;34:1583–93.

    Article  PubMed  CAS  Google Scholar 

  11. Vliegen RF, Beets-Tan RG, Vanhauten B, Driessen A, Oellers M, Kessels AG, et al. Can an FDGPET/CT predict tumor clearance of the mesorectal fascia after preoperative chemoradiation of locally advanced rectal cancer? Strahlenther Onkol. 2008;184:457–64.

    Article  PubMed  Google Scholar 

  12. Janssen MH, Öllers MC, van Stiphout RG, Riedl RG, van den Bogaard J, Buijsen J, et al. PET-based treatment response evaluation in rectal cancer prediction and validation. Int J Radiat Oncol Biol Phys. 2012;82:871–6.

    Article  PubMed  Google Scholar 

  13. 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 

  14. Kalff V, Duong C, Drummond EG, Matthews JP, Hicks RJ. Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery. J Nucl Med. 2006;47:14–22.

    PubMed  Google Scholar 

  15. Calvo FA, Domper M, Matute R, Martínez-Lázaro R, Arranz JA, Desco M, et al. PET imaging in rectal cancer 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 

  16. Calvo FA, Cabezón L, González C, Soria A, de la Mata D, Gómez-Espí M, et al. PET imaging in rectal cancer 18F-FDG PET bio-metabolic monitoring of neoadjuvant therapy effects in rectal cancer: focus on nodal disease characteristics. Radiother Oncol. 2010;97:212–6.

    Article  PubMed  Google Scholar 

  17. Calvo FA, Serrano FJ, Diaz-González JA, Gomez-Espi M, Lozano E, Garcia R, et al. Improved incidence of pT0 downstaged surgical specimens in locally advanced rectal cancer (LARC) treated with induction oxaliplatin plus 5-fluorouracil and preoperative chemoradiation. Ann Oncol. 2006;17:1103–10.

    Article  PubMed  CAS  Google Scholar 

  18. Calvo FA, Gomez-Espi M, Diaz-Gonzalez JA, Alvarado A, Cantalapiedra R, Marcos P, et al. Intraoperative presacral electron boost following preoperative chemoradiation in T3-4Nx rectal cancer: initial local effects and clinical outcome analysis. Radiother Oncol. 2002;62:201–6.

    Article  PubMed  Google Scholar 

  19. Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumor spread and surgical excision. Lancet. 1986;2:996–9.

    Article  PubMed  CAS  Google Scholar 

  20. American Joint Committee on Cancer. General information on cancer staging and end-results reporting. In: Cancer Staging Handbook. Seventh edition, Heidelberg: Springer; 2007. p. 1–39.

  21. 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 

  22. Beaulieu S, Kinahan P, Tseng J, Dunnwald LK, Schubert EK, Pham P, et al. SUV varies with time after injection in (18)F-FDG PET of breast cancer: characterization and method to adjust for time differences. J Nucl Med. 2003;44:1044–50.

    PubMed  Google Scholar 

  23. Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med. 2004;45:1519–27.

    PubMed  Google Scholar 

  24. Gosens MJ, Dresen RC, Rutten HJ, Nieuwenhuijzen GA, van der Laak JA, Martijn H, et al. Preoperative radiochemotherapy is successful also in patients with locally advanced rectal cancer who have intrinsically high apoptotic tumours. Ann Oncol. 2008;19:2026–32.

    Article  PubMed  CAS  Google Scholar 

  25. Valentini V, van Stiphout R, Lammering G, Gambacorta MA, Barba MC, Bebenek M, et al. Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials. J Clin Oncol. 2011;29:3163–72.

    Article  PubMed  Google Scholar 

  26. Glynne-Jones R, Hughes R. Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 2012;99:897–909.

    Article  PubMed  CAS  Google Scholar 

  27. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.

    Article  PubMed  CAS  Google Scholar 

  28. Rau B, Hunerbein M, Barth C, Wust P, Haensch W, Riess H, et al. Accuracy of endorectal ultrasound after preoperative radiochemotherapy in locally advanced rectal cancer. Surg Endosc. 1999;13:980–4.

    Article  PubMed  CAS  Google Scholar 

  29. 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 

  30. 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 

  31. Amthauer H, Denecke T, Rau B, Hildebrandt B, Hünerbein M, Ruf J, et al. Response prediction by FDG-PET after neoadjuvant radiochemotherapy and combined regional hyperthermia of rectal cancer: correlation with endorectal ultrasound and histopathology. Eur J Nucl Med Mol Imaging. 2004;31:811–9.

    Article  PubMed  Google Scholar 

  32. Guillem JG, Moore HG, Akhurst T, Klimstra DS, Ruo L, Mazumdar M, et al. Sequential preoperative fluorodeoxyglucose-positron emission tomography assessment of response to preoperative chemoradiation: a means for determining longterm outcomes of rectal cancer. J Am Coll Surg. 2004;199:1–7.

    Article  PubMed  Google Scholar 

  33. 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 

  34. Avallone A, Aloj L, Caracò C, Delrio P, Pecori B, Tatangelo F, 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. 2012;39:1848–57

    Article  PubMed  CAS  Google Scholar 

  35. 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 

  36. Engenhart R, Kimmig BN, Strauss LG, Höver KH, Romahn J, Haberkorn U, et al. Therapy monitoring of presacral recurrences after high-dose irradiation: value of PET, CT, CEA and pain score. Strahlenther Onkol. 1992;168:203–12.

    PubMed  CAS  Google Scholar 

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Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Oncology, Hospital General Universitario Gregorio Marañón, Ave. Doctor Esquerdo 46, 28007, Madrid, Spain

    Felipe A. Calvo & Claudio V. Sole

  2. School of Medicine Complutense University, Ciudad Universitaria, 28040, Madrid, Spain

    Felipe A. Calvo, Claudio V. Sole, Emilio Alvarez & José L. Carreras

  3. Service of Radiation Oncology, Instituto de Radiomedicina, Ave. Americo Vespucio norte 1314, Santiago, Chile

    Claudio V. Sole

  4. Service of Radiation Oncology, Hospital General Universitario Gregorio Marañón, Ave. Doctor Esquerdo 46, 28007, Madrid, Spain

    Dolores de la Mata & Marina Gómez-Espí

  5. Service of Medical Oncology, Hospital General Universitario Gregorio Marañón, Ave. Doctor Esquerdo 46, 28007, Madrid, Spain

    Luis Cabezón

  6. Department of Pathology, Hospital General Universitario Gregorio Marañón, Ave. Doctor Esquerdo 46, 28007, Madrid, Spain

    Emilio Alvarez

  7. Service of Nuclear Medicine, Clinica La Luz, Ave. General Rodrigo 8, 28003, Madrid, Spain

    Paz Madariaga & José L. Carreras

  8. Service of Nuclear Medicine, Hospital Clinico San Carlos, Ave. Profesor Martin Lagos, 28040, Madrid, Spain

    José L. Carreras

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  1. Felipe A. Calvo
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Corresponding author

Correspondence to Claudio V. Sole.

Additional information

This article is discussed in the editorial commentary available at doi:10.1007/s00259-013-2367-1.

Felipe A. Calvo and Claudio V. Sole contributed equally to this work.

Financed in part by a Research Grant from Mutua Madrileña Biomedical, Foundation Institute Health Research Marañon, study code CMF, FMM 06-02.

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Calvo, F.A., Sole, C.V., de la Mata, D. et al. 18F-FDG PET/CT-based treatment response evaluation in locally advanced rectal cancer: a prospective validation of long-term outcomes. Eur J Nucl Med Mol Imaging 40, 657–667 (2013). https://doi.org/10.1007/s00259-013-2341-y

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  • DOI: https://doi.org/10.1007/s00259-013-2341-y

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