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Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy

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Abstract

Purpose

The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard.

Methods

Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3–5).

Results

SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p < 0.01) with a ROC curve cut-off values of 5.1, 2.1 cm3, 23.4 cm3, 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG.

Conclusion

FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG.

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References

  1. Delbeke D, Walker R. Colorectal Cancer”. In: Delbeke D, Israel O, editors. Hybrid PET/CT and SPECT/CT imaging. Springer; 2010. p. 261–92.

  2. Gil-delgado MA, Khayat D. Cancro del colon e del retto. In: Pollock RE, Doroshok JH, Khayat D, Nakao A, O’Sullivah B, editors. UICC manuale di oncologia clinica. Minerva medica; 2008, VIII ed. p. 511–29.

  3. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23. Erratum in: N Engl J Med. 2007;357(7):728.

    Article  PubMed  CAS  Google Scholar 

  4. De Paoli A, Chiara S, Luppi G, Friso ML, Beretta GD, Del Prete S, et al. Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol. 2006;17(2):246–51.

    Article  PubMed  Google Scholar 

  5. Graf W, Dahlberg M, Osman MM, Holmberg L, Pählman L, Glimelius B. Short-term preoperative radiotherapy results in down-staging of rectal cancer: a study of 1316 patients. Radiother Oncol. 1997;43(2):133–7.

    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(34):8688–96.

    Article  PubMed  Google Scholar 

  7. Rosenberg R, Nekarda H, Zimmermann F, Becker K, Lordick F, Hofler H, et al. Histopathological response after preoperative radiochemotherapy in rectal carcinoma is associated with improved overall survival. J Surg Oncol. 2008;97(1):8–13.

    Article  PubMed  CAS  Google Scholar 

  8. Medich D, McGinty J, Parda D, Karlovits S, Davis C, Caushaj P, et al. Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma: pathologic findings and clinical implications. Dis Colon Rectum. 2001;44(8):1123–8.

    Article  PubMed  CAS  Google Scholar 

  9. Habr-Gama A, Perez RO, Nadalin W, Nahas SC, Ribeiro Jr U, Silva E, et al. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005;9(1):90–9.

    Article  PubMed  Google Scholar 

  10. Valentini V, Coco C, Cellini N, Picciocchi A, Fares MC, Rosetto ME, et al. Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies. Int J Radiat Oncol Biol Phys. 2001;51(2):371–83.

    Article  PubMed  CAS  Google Scholar 

  11. 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(2):W202–8.

    Article  PubMed  Google Scholar 

  12. Huh JW, Min JJ, Lee JH, Kim HR, Kim YJ. The predictive role of sequential FDG-PET/CT in response of locally advanced rectal cancer to neoadjuvant chemoradiation. Am J Clin Oncol. 2012;35(4):340–4.

    Article  PubMed  Google Scholar 

  13. 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(4):711–7.

    PubMed  Google Scholar 

  14. Capirci C, Rubello D, Pasini F, Galeotti F, Bianchini E, Del Favero G, et al. The role of dual-time combined 18-fluorodeoxyglucose positron emission tomography and computed tomography in the staging and restaging workup of locally advanced rectal cancer, treated with preoperative chemoradiation therapy and radical surgery. Int J Radiat Oncol Biol Phys. 2009;74(5):1461–9.

    Article  PubMed  Google Scholar 

  15. Melton GB, Lavely WC, Jacene HA, Schulick RD, Choti MA, Wahl RL, et al. Efficacy of preoperative combined 18-fluorodeoxyglucose positron emission tomography and computed tomography for assessing primary rectal cancer response to neoadjuvant therapy. J Gastrointest Surg. 2007;11(8):961–9.

    Article  PubMed  Google Scholar 

  16. 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(10):1583–93.

    Article  PubMed  CAS  Google Scholar 

  17. Capirci C, Rubello D, Chierichetti F, Crepaldi G, Carpi A, Nicolini A, et al. Restaging after neoadjuvant chemoradiotherapy for rectal adenocarcinoma: role of F18-FDG PET. Biomed Pharmacother. 2004;58(8):451–7.

    PubMed  CAS  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. Costelloe CM, Chuang HH, Madewell JE, Ueno NT. Cancer response criteria and bone metastases: RECIST 1.1, MDA and PERCIST. J Cancer. 2010;1:80–92.

    Article  PubMed  Google Scholar 

  20. International Atomic Energy Agency. The role of PET/CT in radiation treatment planning for cancer patient treatment. Vienna: IAEA; 2008.

    Google Scholar 

  21. International Atomic Energy Agency. Appropriate use of FDG-PET for the management of cancer patients. Vienna: IAEA; 2010.

    Google Scholar 

  22. Ferretti A, Bellan E, Gava M, Chondrogiannis S, Massaro A, Nibale O, et al. Phantom study of the impact of reconstruction parameters on the detection of mini- and micro-volume lesions with a low-dose PET/CT acquisition protocol. Eur J Radiol. 2012;81(11):3363–70.

    Article  PubMed  Google Scholar 

  23. Erselcan T, Turgut B, Dogan D, Ozdemir S. Lean body mass-based standardized uptake value, derived from a predictive equation, might be misleading in PET studies. Eur J Nucl Med Mol Imaging. 2002;29:1630–8.

    Article  PubMed  Google Scholar 

  24. Paquet N, Albert A, Foidart J, Hustinx R. Within patient variability of 18F-FDG: standardized uptake values in normal tissues. J Nucl Med. 2004;45:784–8.

    PubMed  CAS  Google Scholar 

  25. Stahl A, Ott K, Schwaiger M, Weber WA. Comparison of different SUV-based methods for monitoring cytotoxic therapy with FDG PET. Eur J Nucl Med Mol Imaging. 2004;31:1471–8.

    Article  PubMed  CAS  Google Scholar 

  26. 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(3):159–71.

    Article  PubMed  Google Scholar 

  27. Lee JA. Segmentation of positron emission tomography images: some recommendations for target delineation in radiation oncology. Radiother Oncol. 2010;96(3):302–7.

    Article  PubMed  Google Scholar 

  28. Capirci C, Valvo F, Salviato S. Concurrent boost radiotherapy as preoperative treatment for locally advanced rectal carcinoma: a new beam arrangement. Tumori. 2002;88:325–30.

    PubMed  Google Scholar 

  29. Capirci C, Polico C, Mandoliti G. Dislocation of small bowel volume within box pelvic treatment fields, using the new “Up Down Table” device. Int J Radiat Oncol Biol Phys. 2002;88:325–30.

    Google Scholar 

  30. Quirke P, Dixon MF. The prediction of local recurrence in rectal adenocarcinoma by histopathological examination. Int J Colon Dis. 1988;3:127–31.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Augestad KM, Lindsetmo RO, Stulberg J, Reynolds H, Senagore A, Champagne B, et al. International preoperative rectal cancer management: staging, neoadjuvant treatment, and impact of multidisciplinary teams. World J Surg. 2010;34:2689–700.

    Article  PubMed  Google Scholar 

  33. Deneke T, Rau B, Hoffmann KT. Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: is there a benefit in using functional imaging? Eur Radiol. 2005;15:1658–66.

    Article  Google Scholar 

  34. Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, et al. Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol. 2002;20:379–87.

    Article  PubMed  CAS  Google Scholar 

  35. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Rectal cancer. Table of Contents Discussion, Version 3.2013, table MS-16, www.nccn.org. Accessed 1 Sep 2012.

  36. Erdi YE, Mawlawi O, Larson SM, Imbriaco M, Yeung H, Finn R, et al. Segmentation of lung lesion volume by adaptive PET image thresholding. Cancer. 1997;80 Suppl 12:2505–9.

    Article  PubMed  CAS  Google Scholar 

  37. Ippolito D, Monguzzi L, Guerra L, Deponti E, Gardani G, Messa C, et al. Response to neoadjuvant therapy in locally advanced rectal cancer: assessment with diffusion-weighted MR imaging and 18FDG PET/CT. Abdom Imaging. 2012;37:1032–40.

    Article  PubMed  Google Scholar 

  38. 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):1–7.

    Article  PubMed  Google Scholar 

  39. Kristiansen C, Loft A, Berthelsen AK, Graff J, Lindebjerg J, Bisgaard C, et al. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer. Dis Colon Rectum. 2008;51(1):21–5.

    Article  PubMed  Google Scholar 

  40. 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(3):650–6.

    Article  PubMed  CAS  Google Scholar 

  41. Shanmugan S, Arrangoiz R, Nitzkorski JR, Yu JQ, Li T, Cooper H, et al. Predicting pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using 18FDG-PET/CT. Ann Surg Oncol. 2012;19(7):2178–85.

    Article  PubMed  Google Scholar 

  42. Chennupati SK, Quon A, Kamaya A, Pai RK, La T, Krakow TE, et al. Positron emission tomography for predicting pathologic response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Am J Clin Oncol. 2012;35(4):334–9.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Nuclear Medicine Department, PET unit, Santa Maria della Misericordia Hospital, Rovigo, Italy

    Anna Margherita Maffione, Alice Ferretti, Gaia Grassetto, Sotirios Chondrogiannis, Maria Cristina Marzola, Lucia Rampin, Claudia Bondesan & Domenico Rubello

  2. Medical Physics Department, Santa Maria della Misericordia Hospital, Rovigo, Italy

    Alice Ferretti, Elena Bellan & Marcello Gava

  3. Radiotherapy Department, Santa Maria della Misericordia Hospital, Rovigo, Italy

    Carlo Capirci

  4. Department of Radiology, University of Southern California, Los Angeles, CA, 90033, USA

    Patrick M. Colletti

  5. SOC Medicina Nucleare, Santa Maria della Misericordia Hospital, Viale Tre Martiri, 140, 45100, Rovigo, Italy

    Anna Margherita Maffione

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  1. Anna Margherita Maffione
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Correspondence to Anna Margherita Maffione.

Additional information

Anna Margherita Maffione and Alice Ferretti contributed equally to the preparation of the manuscript.

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Maffione, A.M., Ferretti, A., Grassetto, G. et al. Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy. Eur J Nucl Med Mol Imaging 40, 853–864 (2013). https://doi.org/10.1007/s00259-013-2357-3

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