Monitoring chemotherapy and radiotherapy of solid tumors



PET imaging with the glucose analog fluorodeoxyglucose (FDG-PET) has been evaluated in numerous studies to monitor tumor response in patients undergoing chemo- and radiotherapy. The clinical value of FDG-PET for differentiation of residual or recurrent viable tumor and therapy-induced fibrosis or scar tissue has been documented for various solid tumors. Furthermore, there are now several reports suggesting that quantitative assessment of therapy-induced changes in tumor FDG uptake may allow prediction of tumor response and patient outcome very early in the course of therapy. In nonresponding patients, treatment may be adjusted according to the individual chemo- and radiosensitivity of the tumor tissue. Since the number of alternative treatments for solid tumors (e.g., second-line chemotherapy agents, protein kinase, or angiogenesis inhibitors) is continuously increasing, early prediction of tumor response to chemotherapy and radiotherapy by FDG-PET has enormous potential to “personalize” treatment and to reduce the side-effects and costs of ineffective therapy.


Fluorodeoxyglucose Positron emission tomography Chemotherapy Radiotherapy Response Prognosis 


  1. 1.
    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;92:205–216PubMedCrossRefGoogle Scholar
  2. 2.
    Buyse M, Thirion P, Carlson RW, Burzykowski T, Molenberghs G, Piedbois P. Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-Analysis Group in Cancer. Lancet 2000;356:373–378PubMedCrossRefGoogle Scholar
  3. 3.
    Bruzzi P, Del Mastro L, Sormani MP, Bastholt L, Danova M, Focan C, et al. Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients. J Clin Oncol 2005;23:5117–5125PubMedCrossRefGoogle Scholar
  4. 4.
    Ratain MJ. Phase II oncology trials: let’s be positive. Clin Cancer Res 2005;11:5661–5662PubMedCrossRefGoogle Scholar
  5. 5.
    Goffin J, Baral S, Tu D, Nomikos D, Seymour L. Objective responses in patients with malignant melanoma or renal cell cancer in early clinical studies do not predict regulatory approval. Clin Cancer Res 2005;11:5928–5934PubMedCrossRefGoogle Scholar
  6. 6.
    Salzer-Kuntschik M, Delling G, Beron G, Sigmund R. Morphological grades of regression in osteosarcoma after polychemotherapy—study COSS 80. J Cancer Res Clin Oncol 1983;106(Suppl):21–24PubMedCrossRefGoogle Scholar
  7. 7.
    Junker K, Langner K, Klinke F, Bosse U, Thomas M. Grading of tumor regression in non-small cell lung cancer: morphology and prognosis. Chest 2001;120:1584–1591PubMedCrossRefGoogle Scholar
  8. 8.
    Mandard A, Dalibard F, Mandard J, Marnay J, Henry-Amar M, Petiot J, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994;73:2680–2686PubMedCrossRefGoogle Scholar
  9. 9.
    Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer 2003;98:1521–1530PubMedCrossRefGoogle Scholar
  10. 10.
    Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20:776–790PubMedCrossRefGoogle Scholar
  11. 11.
    Wieder HA, Brucher BL, Zimmermann F, Becker K, Lordick F, Beer A, et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol 2004;22:900–908PubMedCrossRefGoogle Scholar
  12. 12.
    Brucher BL, Weber W, Bauer M, Fink U, Avril N, Stein HJ, et al. Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography. Ann Surg 2001;233:300–309PubMedCrossRefGoogle Scholar
  13. 13.
    Flamen P, Van Cutsem E, Lerut A, Cambier J, Haustermans K, Bormans G, et al. Positron emission tomography for assessment of the response to induction chemotherapy in locally advanced esophageal cancer. Ann Oncol 2002;13:361–368PubMedCrossRefGoogle Scholar
  14. 14.
    Downey RJ, Akhurst T, Ilson D, Ginsberg R, Bains MS, Gonen M, et al. Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol 2003;21:428–432PubMedCrossRefGoogle Scholar
  15. 15.
    Swisher SG, Maish M, Erasmus JJ, Correa AM, Ajani JA, Bresalier R, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg 2004;78:1152–60, discussion 1152–1160PubMedCrossRefGoogle Scholar
  16. 16.
    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;101:1776–1785PubMedCrossRefGoogle Scholar
  17. 17.
    MacManus 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;21:1285–1292CrossRefGoogle Scholar
  18. 18.
    Hellwig D, Graeter TP, Ukena D, Georg T, Kirsch CM, Schafers HJ. Value of F-18-fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma. J Thorac Cardiovasc Surg 2004;128:892–899PubMedCrossRefGoogle Scholar
  19. 19.
    Akhurst T, Downey RJ, Ginsberg MS, Gonen M, Bains M, Korst R, et al. An initial experience with FDG-PET in the imaging of residual disease after induction therapy for lung cancer. Ann Thorac Surg 2002;73:259–64, discussion 264–266PubMedCrossRefGoogle Scholar
  20. 20.
    Ryu JS, Choi NC, Fischman AJ, Lynch TJ, Mathisen DJ. FDG-PET in staging and restaging non-small cell lung cancer after neoadjuvant chemoradiotherapy: correlation with histopathology. Lung Cancer 2002;35:179–187PubMedCrossRefGoogle Scholar
  21. 21.
    Cerfolio RJ, Bryant AS, Winokur TS, Ohja B, Bartolucci AA. Repeat FDG-PET after neoadjuvant therapy is a predictor of pathologic response in patients with non-small cell lung cancer. Ann Thorac Surg 2004;78:1903–1909, discussion 1909PubMedCrossRefGoogle Scholar
  22. 22.
    Port JL, Kent MS, Korst RJ, Keresztes R, Levin MA, Altorki NK. Positron emission tomography scanning poorly predicts response to preoperative chemotherapy in non-small cell lung cancer. Ann Thorac Surg 2004;77:254–259, discussion 259PubMedCrossRefGoogle Scholar
  23. 23.
    Grigsby PW, Siegel BA, Dehdashti F, Rader J, Zoberi I. Posttherapy [18F]fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: response and outcome. J Clin Oncol 2004;22:2167–2171PubMedCrossRefGoogle Scholar
  24. 24.
    Schuetze SM, Rubin BP, Vernon C, Hawkins DS, Bruckner JD, Conrad EU 3rd, et al. Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy. Cancer 2005;103:339–348PubMedCrossRefGoogle Scholar
  25. 25.
    Schulte M, Brecht-Krauss D, Werner M, Hartwig E, Sarkar MR, Keppler P, et al. Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG PET. J Nucl Med 1999;40:1637–1643PubMedGoogle Scholar
  26. 26.
    Hawkins DS, Rajendran JG, Conrad EU 3rd, Bruckner JD, Eary JF. Evaluation of chemotherapy response in pediatric bone sarcomas by [F-18]-fluorodeoxy-D-glucose positron emission tomography. Cancer 2002;94:3277–3284PubMedCrossRefGoogle Scholar
  27. 27.
    Wahl RL, Zasadny K, Helvie M, Hutchins GD, Weber B, Cody R. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 1993;11:2101–2111PubMedGoogle Scholar
  28. 28.
    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;13:1470–1477PubMedGoogle Scholar
  29. 29.
    Findlay M, Young H, Cunningham D, Iveson A, Cronin B, Hickish T, et al. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. J Clin Oncol 1996;14:700–708PubMedGoogle Scholar
  30. 30.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92–98PubMedCrossRefGoogle Scholar
  31. 31.
    Honkoop AH, van Diest PJ, de Jong JS, Linn SC, Giaccone G, Hoekman K, et al. Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer. Br J Cancer 1998;77:621–626PubMedGoogle Scholar
  32. 32.
    Smith IC, Welch AE, Hutcheon AW, Miller ID, Payne S, Chilcott F, et al. Positron emission tomography using [18F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 2000;18:1676–1688PubMedGoogle Scholar
  33. 33.
    Schelling M, Avril N, Nahrig J, Kuhn W, Romer W, Sattler D, et al. Positron emission tomography using [18F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 2000;18:1689–1695PubMedGoogle Scholar
  34. 34.
    Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Schubert EK, Tseng J, et al. Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J Nucl Med 2003;44:1806–1814PubMedGoogle Scholar
  35. 35.
    Kelsen DP, Minsky B, Smith M, Beitler J, Niedzwiecki D, Chapman D, et al. Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy. J Clin Oncol 1990;8:1352–1361PubMedGoogle Scholar
  36. 36.
    Medical Research Council. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 2002;359:1727–1733CrossRefGoogle Scholar
  37. 37.
    Kelsen D. Preoperative chemoradiotherapy for esophageal cancer. J Clin Oncol 2001;19:283–285PubMedGoogle Scholar
  38. 38.
    Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19:305–313PubMedGoogle Scholar
  39. 39.
    Ajani JA, Mansfield PF, Lynch PM, Pisters PW, Feig B, Dumas P, et al. Enhanced staging and all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma. J Clin Oncol 1999;17:2403–411PubMedGoogle Scholar
  40. 40.
    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;19:3058–3065PubMedGoogle Scholar
  41. 41.
    Ott K, Fink U, Becker K, Stahl A, Dittler HJ, Busch R, et al. Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J Clin Oncol 2003;21:4604–4610PubMedCrossRefGoogle Scholar
  42. 42.
    Hoekstra CJ, Stroobants SG, Smit EF, Vansteenkiste J, van Tinteren H, Postmus PE, et al. Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer. J Clin Oncol 2005;23:8362–8370PubMedCrossRefGoogle Scholar
  43. 43.
    Avril N, Sassen S, Schmalfeldt B, Naehrig J, Rutke S, Weber WA, et al. Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer. J Clin Oncol 2005;23:7445–7453PubMedCrossRefGoogle Scholar
  44. 44.
    Haberkorn U, Morr I, Oberdorfer F, Bellemann ME, Blatter J, Altmann A, et al. Fluorodeoxyglucose uptake in vitro: aspects of method and effects of treatment with gemcitabine. J Nucl Med 1994;35:1842–1850PubMedGoogle Scholar
  45. 45.
    Higashi K, Clavo AC, Wahl RL. In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy [see comments]. J Nucl Med 1993;34:773–779PubMedGoogle Scholar
  46. 46.
    Rozental JM, Levine RL, Nickles RJ, Dobkin JA. Glucose uptake by gliomas after treatment. A positron emission tomographic study [see comments]. Arch Neurol 1989;46:1302–1307PubMedGoogle Scholar
  47. 47.
    Maruyama I, Sadato N, Waki A, Tsuchida T, Yoshida M, Fujibayashi Y, et al. Hyperacute changes in glucose metabolism of brain tumors after stereotactic radiosurgery: a PET study. J Nucl Med 1999;40:1085–1090PubMedGoogle Scholar
  48. 48.
    Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 2001;19:2797–2803PubMedGoogle Scholar
  49. 49.
    Hicks RJ, MacManus MP, Matthews JP, Hogg A, Binns D, Rischin D, et al. Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation. Int J Radiat Oncol Biol Phys 2004;60:412–418PubMedCrossRefGoogle Scholar
  50. 50.
    Amthauer H, Denecke T, Rau B, Hildebrandt B, Hunerbein 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;31:811–819PubMedCrossRefGoogle Scholar
  51. 51.
    Pottgen C, Levegrun S, Theegarten D, Marnitz S, Grehl S, Pink R, et al. Value of 18F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in non-small-cell lung cancer for prediction of pathologic response and times to relapse after neoadjuvant chemoradiotherapy. Clin Cancer Res 2006;12:97–106PubMedCrossRefGoogle Scholar
  52. 52.
    Townsend DW, Carney JP, Yap JT, Hall NC. PET/CT today and tomorrow. J Nucl Med 2004;45(Suppl 1):4S–14SPubMedGoogle Scholar
  53. 53.
    Goerres GW, Burger C, Kamel E, Seifert B, Kaim AH, Buck A, et al. Respiration-induced attenuation artifact at PET/CT: technical considerations. Radiology 2003;226:906–910PubMedCrossRefGoogle Scholar
  54. 54.
    Pan T, Mawlawi O, Nehmeh SA, Erdi YE, Luo D, Liu HH, et al. Attenuation correction of PET images with respiration-averaged CT images in PET/CT. J Nucl Med 2005;46:1481–1487PubMedGoogle Scholar
  55. 55.
    Berthelsen AK, Holm S, Loft A, Klausen TL, Andersen F, Hojgaard L. PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients. Eur J Nucl Med Mol Imaging 2005;32:1167–1175PubMedCrossRefGoogle Scholar
  56. 56.
    Beer A, Wieder H, Lordick F, Ott K, Fischer M, Becker K, et al. Adenocarcinomas of the esophagogastric junction: MDCT for evaluation of early response to neoadjuvant chemotherapy. Radiology 2006;Mar 16 [Epub ahead of print]Google Scholar
  57. 57.
    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;2:159–171PubMedCrossRefGoogle Scholar
  58. 58.
    Young H, Baum R, Cremerius U, Herholz K, Hoeckstra O, Lammertsma A, et al. Measurement of clinical and sublinical tumour response using f-18-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. Eur J Cancer 1999;35:1773–1782PubMedCrossRefGoogle Scholar
  59. 59.
    Minn H, Zasadny KR, Quint LE, Wahl RL. Lung cancer: reproducibility of quantitative measurements for evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET. Radiology 1995;196:167–173PubMedGoogle Scholar
  60. 60.
    Weber WA, Ziegler SI, Thodtmann R, Hanauske AR, Schwaiger M. Reproducibility of metabolic measurements in malignant tumors using FDG PET. J Nucl Med 1999;40:1771–1777PubMedGoogle Scholar
  61. 61.
    Weber WA, Petersen V, Schmidt B, Tyndale-Hines L, Link T, Peschel C, et al. Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol 2003;21:2651–2657PubMedCrossRefGoogle Scholar
  62. 62.
    Yamane T, Daimaru O, Ito S, Yoshiya K, Nagata T, Uchida H. Decreased 18F-FDG uptake 1 day after initiation of chemotherapy for malignant lymphomas. J Nucl Med 2004;45:1838–1842PubMedGoogle Scholar
  63. 63.
    Weber WA, Ott K. Imaging of esophageal and gastric cancer. Semin Oncol 2004;31:530–541PubMedCrossRefGoogle Scholar
  64. 64.
    Brun E, Kjellen E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck 2002;24:127–135PubMedCrossRefGoogle Scholar
  65. 65.
    Lordick F, Weber WA, Stein HJ, Schuhmacher C, Beer A, Hennig M, et al. Individualized neoadjuvant treatment strategy in adenocarcinoma of the esophago-gastric junction (AEG): interim report on the MUNICON trial. J Clin Oncol 2004;22:328SGoogle Scholar
  66. 66.
    Kunkel M, Forster GJ, Reichert TE, Kutzner J, Benz P, Bartenstein P, et al. Radiation response non-invasively imaged by [18F]FDG-PET predicts local tumor control and survival in advanced oral squamous cell carcinoma. Oral Oncol 2003;39:170–177PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging CenterUCLA David Geffen School of MedicineLos AngelesUSA
  2. 2.Nuklearmedizinische Klinik und PoliklinikTechnische Universität MünchenMunichGermany

Personalised recommendations