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Response prediction by FDG-PET after neoadjuvant radiochemotherapy and combined regional hyperthermia of rectal cancer: correlation with endorectal ultrasound and histopathology

  • Holger AmthauerEmail author
  • Timm Denecke
  • Beate Rau
  • Bert Hildebrandt
  • Michael Hünerbein
  • Juri Ruf
  • Ulrike Schneider
  • Matthias Gutberlet
  • Peter M. Schlag
  • Roland Felix
  • Peter Wust
Original Article

Abstract

Accurate response assessment after neoadjuvant therapy is essential in patients with rectal cancer. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting response of locally advanced rectal cancer to preoperative multimodal treatment. Twenty-two consecutive patients with locally advanced (uT3/4) primary rectal cancer were entered in this prospective pilot study. FDG-PET was performed before and after neoadjuvant radiochemotherapy (RCT) with combined regional hyperthermia (RHT). Treatment consisted of external-beam radiotherapy (45 Gy), chemotherapy (folinic acid and 5-fluorouracil) and regional pelvic hyperthermia followed by curative tumour resection 6–8 weeks later. Semi-quantitative measurements (SUV) of tumour FDG uptake were made before and 2–4 weeks after completion of neoadjuvant treatment. Two patients who did not receive post-therapeutic restaging by FDG-PET were excluded from the analysis. Results were correlated with findings on endorectal ultrasound (EUS, n=17 patients) and histopathology. Histopathological evaluation of the resected tumour revealed complete response in one patient, partial response in 12 and stable disease in seven. SUV reduction in tumours was significantly greater in responders than in non-responders [60% (±15%) vs 30% (±18%), P=0.003, CI=95%). Using a minimum post-therapeutic SUV reduction of 36% to define response, FDG-PET revealed a sensitivity of 100% (EUS: 33%) and a specificity of 86% (EUS: 80%) in response prediction; the corresponding positive and negative predictive values were 93% (EUS: 80%) and 100% (EUS: 33%), respectively. FDG-PET results were statistically significant (P<0.001, CI=95%). FDG-PET has great potential in the assessment of tumour response to neoadjuvant RCT in combination with RHT and is superior to EUS for this purpose.

Keywords

Rectal cancer Neoadjuvant therapy PET Endorectal ultrasound Response 

Notes

Acknowledgement

This study was supported by the Deutsche Forschungsgemeinschaft as part of the project Graduiertenkolleg 331—”Temperaturabhängige Effekte in Therapie und Diagnostik” and the project SFB 273—”Hyperthermia: Methodics and Clinics”.

References

  1. 1.
    NIH, NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990; 264:1444–1450.PubMedGoogle Scholar
  2. 2.
    Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000; 92:388–396.CrossRefPubMedGoogle Scholar
  3. 3.
    Minsky BD, Cohen AM, Kemeny N, Enker WE, Kelsen DP, Reichman B, Saltz L, Sigurdson ER, Frankel J. Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy. J Clin Oncol 1992; 10:79–84.PubMedGoogle Scholar
  4. 4.
    Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001; 358:1291–1304.CrossRefPubMedGoogle Scholar
  5. 5.
    Sauer R, Fietkau R, Wittekind C, Martus P, Rodel C, Hohenberger W, Jatzko G, Sabitzer H, Karstens JH, Becker H, Hess C, Raab R. Adjuvant versus neoadjuvant radiochemotherapy for locally advanced rectal cancer. A progress report of a phase-III randomized trial (protocol CAO/ARO/AIO-94). Strahlenther Onkol 2001; 177:173–181.PubMedGoogle Scholar
  6. 6.
    Rau B, Huenerbein M, Barth C, Wust P, Haensch W, Riess H, Felix R, Schlag PM. Accuracy of endorectal ultrasound after preoperative radiochemotherapy in locally advanced rectal cancer. Surg Endosc 1999; 13:980–984.CrossRefPubMedGoogle Scholar
  7. 7.
    Hoffmann KT, Rau B, Wust P, Stroszczynski C, Hunerbein M, Schneider U, Felix R. Re-staging of locally advanced carcinoma of the rectum with MR imaging after preoperative radio-chemotherapy plus regional hyperthermia. Strahlenther Onkol 2002; 178:386–392.CrossRefGoogle Scholar
  8. 8.
    Kahn H, Alexander A, Rakinic J, Nagle D, Fry R. Preoperative staging of irradiated rectal cancers using digital rectal examination, computed tomography, endorectal ultrasound, and magnetic resonance imaging does not accurately predict T0,N0 pathology. Dis Colon Rectum 1997; 34:748–751.Google Scholar
  9. 9.
    Rau B, Wust P, Hohenberger P, Loffel J, Hunerbein M, Below C, Gellermann J, Speidel A, Vogl T, Riess H, Felix R, Schlag PM. Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: a phase II clinical trial. Ann Surg 1998; 227:380–389.Google Scholar
  10. 10.
    Mohiuddin M, Regine WF, Marks GJ, Marks JW. High-dose preoperative radiation and the challenge of sphincter-preservation surgery for cancer of the distal 2 cm of the rectum. Int J Radiat Oncol Biol Phys 1998; 40:569–574.Google Scholar
  11. 11.
    Willett CG, Shellito PC, Tepper JE, Eliseo R, Convery K, Wood W. Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma. Chirurg 1991; 67:1504–1508.Google Scholar
  12. 12.
    Kim JS, Kim JS, Cho MJ, Song KS, Yoon WH. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2002; 54:403–408.CrossRefPubMedGoogle Scholar
  13. 13.
    Bruecher B, Weber W, Bauer M, Fink U, Avril N, Stein HJ, Werner M, Zimmerman F, Siewert JR, Schwaiger M. Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography. Ann Surg 2001; 233:300–309.PubMedGoogle Scholar
  14. 14.
    Lowe VJ, Dunphy FR, Varvares M, Kim H, Wittry M, Dunphy CH, Dunleavy T, McDonough E, Minster J, Fletcher JW, Boyd JH. Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography. Head Neck 1997; 19:666–674.CrossRefPubMedGoogle Scholar
  15. 15.
    Schulte M, Brecht-Krauss D, Werner M, Hartwig E, Sarkar MR, Keppler P, Kotzerke J, Guhlmann A, Delling G, Reske SN. Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG PET. J Nucl Med 1999; 40:1637–1643.PubMedGoogle Scholar
  16. 16.
    Huenerbein M, Below C, Schlag PM. Three-dimensional endorectal ultrasound for staging of obstructing rectal cancer. Dis Colon Rectum 1996; 39:636–642.PubMedGoogle Scholar
  17. 17.
    Glaser F, Schlag P, Herfarth C. Endorectal ultrasonography for the assessment of invasion of rectal tumours and lymph node involvement. Br J Surg 1990; 77:883–887.PubMedGoogle Scholar
  18. 18.
    Rau B, Wust P, Tilly W, Gellermann J, Harder C, Riess H, Budach V, Felix R, Schlag PM. Preoperative radio-chemotherapy in locally advanced recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters. Int J Radiat Oncol Biol Phys 2000; 48:381–391.CrossRefPubMedGoogle Scholar
  19. 19.
    Riess H, Loffel J, Wust P, Rau B, Gremmler M, Speidel A, Schlag P. A pilot study of a new therapeutic approach in the treatment of locally advanced stages of rectal cancer: neoadjuvant radiation, chemotherapy and regional hyperthermia. Eur J Cancer 1995; 31A:1356–1360.CrossRefPubMedGoogle Scholar
  20. 20.
    Sobin LH, Wittekind C. TNM classification of malignant tumours, 5th edn. New York: Wiley, 1997.Google Scholar
  21. 21.
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. 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; 92:205–216.PubMedGoogle Scholar
  22. 22.
    Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987; 317:1098.PubMedGoogle Scholar
  23. 23.
    Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 1999; 35:1773–1782.PubMedGoogle Scholar
  24. 24.
    Metz CE. Some practical issues of experimental design and data analysis in radiological ROC studies. Invest Radiol 1989; 24:234–245.PubMedGoogle Scholar
  25. 25.
    Armitage P, Berry G. Statistical methods in medical research, 3rd edn. Oxford: Blackwell Scientific, 1994.Google Scholar
  26. 26.
    Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet 1996; 348:1605–1610.CrossRefPubMedGoogle Scholar
  27. 27.
    Valentini V, Coco C, Picciocchi A, Morganti AG, Trodella L, Ciabattoni A, Cellini F, Barbaro B, Cogliandolo S, Nuzzo G, Doglietto GB, Ambesi-Impiombato F, Cosimelli M. Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys 2002; 53:664–674.CrossRefPubMedGoogle Scholar
  28. 28.
    Huenerbein M, Pegios W, Rau B, Vogl TJ, Felix R, Schlag PM. Prospective comparison of endorectal ultrasound, three-dimensional endorectal ultrasound, and endorectal MRI in the preoperative evaluation of rectal tumors. Preliminary results. Surg Endosc 2000; 14:1005–1009.CrossRefPubMedGoogle Scholar
  29. 29.
    Beets-Tan RG, Beets GL, Borstlap AC, Oei TK, Teune TM, von Meyenfeldt MF, van Engelshoven JM. Preoperative assessment of local tumor extent in advanced rectal cancer: CT or high-resolution MRI? Abdom Imaging 2000; 25:533–541.CrossRefPubMedGoogle Scholar
  30. 30.
    Williamson PR, Hellinger MD, Larach SW, Ferrara A. Endorectal ultrasound of T3 and T4 rectal cancers after preoperative chemoradiation. Dis Colon Rectum 1996; 39:45–49.PubMedGoogle Scholar
  31. 31.
    Bernini A, Deen KI, Madoff RD, Wong WD. Preoperative adjuvant radiation with chemotherapy for rectal cancer: its impact on stage of disease and the role of endorectal ultrasound. Ann Surg Oncol 1996; 3:131–135.PubMedGoogle Scholar
  32. 32.
    Huebner RH, Park KC, Shepherd JE, Schwimmer J, Czernin J, Phelps ME, Gambhir SS. A meta-analysis of the literature for whole-body FDG PET detection of recurrent colorectal cancer. J Nucl Med 2000; 41:1177–1189.PubMedGoogle Scholar
  33. 33.
    Flier JS, Mueckler MM, Usher P, Lodish HF. Elevates levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 1987; 235:1492–1495.PubMedGoogle Scholar
  34. 34.
    Weber WA, Ott K, Becker K, Dittler HJ, Dittler HJ, Helmberger H, Avril NE, Meisetschlager G, Busch R, Siewert JR, Schwaiger M, Fink U. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 2001; 19:3058–3065.PubMedGoogle Scholar
  35. 35.
    Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, Souquet JC, Adeleine P, Gerard JP. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90–01 randomized trial. J Clin Oncol 1999; 17:2396.PubMedGoogle Scholar
  36. 36.
    Jansson T, Westlin JE, Ahlstrom H, Lilja A, Langstrom B, Bergh J. Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation? J Clin Oncol 1995; 13:1470–1477.PubMedGoogle Scholar
  37. 37.
    Schiepers C, Haustermans K, Geboes K, Filez L, Bormans G, Penninckx F. The effect of preoperative radiation therapy on glucose utilization and cell kinetics in patients with primary rectal carcinoma. Cancer 1999; 85:803–811.CrossRefPubMedGoogle Scholar
  38. 38.
    Haberkorn U, Strauss LG, Dimitrakopoulou A, Engenhart R, Oberdorfer F, Ostertag H, Romahn J, van Kaick G. PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. J Nucl Med 1991; 32:1485–1490.PubMedGoogle Scholar
  39. 39.
    Guillem JG, Puig-La Calle J Jr, Akhurst T, Tickoo S, Ruo L, Minsky BD, Gollub MJ, Klimstra DS, Mazumdar M, Paty PB, Macapinlac H, Yeung H, Saltz L, Finn RD, Erdi Y, Humm J, Cohen AM, Larson S. Prospective assessment of primary rectal cancer response to preoperative radiation and chemotherapy using 18-fluorodeoxyglucose positron emission tomography. Dis Colon Rectum 2000; 43:18–24.PubMedGoogle Scholar
  40. 40.
    Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, Felix R, Schlag PM. Hyperthermia in combined treatment of cancer. Lancet Oncol 2002; 3:487–497.Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Holger Amthauer
    • 1
    Email author
  • Timm Denecke
    • 1
  • Beate Rau
    • 2
  • Bert Hildebrandt
    • 3
  • Michael Hünerbein
    • 2
  • Juri Ruf
    • 1
  • Ulrike Schneider
    • 4
  • Matthias Gutberlet
    • 1
  • Peter M. Schlag
    • 2
  • Roland Felix
    • 1
  • Peter Wust
    • 1
  1. 1.Klinik für Strahlenheilkunde und PET-Zentrum Berlin, Campus Virchow-KlinikumCharité—Universitätsmedizin BerlinBerlinGermany
  2. 2.Klinik für Chirurgie und Chirurgische Onkologie, Campus BuchCharité—Universitätsmedizin BerlinBerlinGermany
  3. 3.Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Campus Virchow-KlinikumCharité—Universitätsmedizin BerlinBerlinGermany
  4. 4.Funktionsbereich Pathologie, Campus BuchCharité—Universitätsmedizin BerlinBerlinGermany

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