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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-06-2004

Measuring response to chemotherapy in locally advanced breast cancer: methodological considerations

Authors: Nanda C. Krak, Otto S. Hoekstra, Adriaan A. Lammertsma

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Special Issue 1/2004

Abstract

In this review the findings of response monitoring studies in breast cancer, using [¹⁸F]2-fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET), are summarised. These studies indicate that there is a strong relationship between response and decrease in FDG signal even at an early stage of therapy. The review concentrates on methodological aspects of monitoring response with FDG: timing of serial scans, approach to region of interest definition, method of quantification and pitfalls of FDG. It is argued that, for clinical applications, there is now a need to standardise methodology. This would be necessary to establish firm cut-off values for discriminating responders from non-responders, which in turn would provide a means for providing optimal treatment for as many patients as possible.

Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998; 16:2672–2685.PubMed

Eltahir A, Heys SD, Hutcheon AW, et al. Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy. Am J Surg 1998; 175:127–132.CrossRefPubMed

Formenti SC, Volm M, Skinner KA, et al. Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: a phase I/II trial. J Clin Oncol 2003; 21:864–870.CrossRefPubMed

Hutcheon AW, Heys SD, Sarkar TK. Neoadjuvant docetaxel in locally advanced breast cancer. Breast Cancer Res Treat 2003; 79 Suppl 1:S19–S24.

Dixon JM, Jackson J, Renshaw L, et al. Neoadjuvant tamoxifen and aromatase inhibitors: comparisons and clinical outcomes. J Steroid Biochem Mol Biol 2003; 86:295–299.CrossRefPubMed

Pinedo HM, de Gruijl TD, van Der Wall E, et al. Biological concepts of prolonged neoadjuvant treatment plus GM-CSF in locally advanced tumors. Oncologist 2000; 5:497–500.PubMed

Moneer M, Ismael S, Khaled H, et al. A new surgical strategy for breast conservation in locally advanced breast cancer that achieves a good locoregional control rate: preliminary report. Breast 2001; 10:220–224.CrossRefPubMed

Stearns V, Ewing CA, Slack R, et al. Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer. Ann Surg Oncol 2002; 9:235–242.CrossRefPubMed

Breslin TM, Cohen L, Sahin A, et al.Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2000; 18:3480–3486.PubMed

10.

Honkoop AH, van Diest PJ, de Jong JS, et al. Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer. Br J Cancer 1998; 77:621–626.PubMed

11.

Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999; 17:460–469.PubMed

12.

Kuerer HM, Newman LA, Buzdar AU, et al. Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer. Am J Surg 1998; 176:502–509.CrossRefPubMed

13.

Machiavelli MR, Romero AO, Perez JE, et al. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma. Cancer J Sci Am 1998; 4:125–131.PubMed

14.

Gajdos C, Tartter PI, Estabrook A, et al. Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer. J Surg Oncol 2002; 80:4–11.CrossRefPubMed

15.

McIntosh SA, Ogston KN, Payne S, et al. Local recurrence in patients with large and locally advanced breast cancer treated with primary chemotherapy. Am J Surg 2003; 185:525–531.CrossRefPubMed

16.

Beenken SW, Urist MM, Zhang Y, et al. Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer. Ann Surg 2003; 237:732–739.CrossRefPubMed

17.

Kuerer HM, Newman LA, Fornage BD, et al. Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer. Ann Surg Oncol 1998; 5:673–680.PubMed

18.

Herrada J, Iyer RB, Atkinson EN, et al. Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma. Clin Cancer Res 1997; 3:1565–1569.PubMed

19.

Helvie MA, Joynt LK, Cody RL, et al. Locally advanced breast carcinoma: accuracy of mammography versus clinical examination in the prediction of residual disease after chemotherapy. Radiology 1996; 198:327–332.PubMed

20.

Rosen EL, Blackwell KL, Baker JA, et al. Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol 2003; 181:1275–1282.PubMed

21.

Delille JP, Slanetz PJ, Yeh ED, et al. Invasive ductal breast carcinoma response to neoadjuvant chemotherapy: noninvasive monitoring with functional MR imaging pilot study. Radiology 2003; 228:63–69.PubMed

22.

Cheung YC, Chen SC, Su MY, et al. Monitoring the size and response of locally advanced breast cancers to neoadjuvant chemotherapy (weekly paclitaxel and epirubicin) with serial enhanced MRI. Breast Cancer Res Treat 2003; 78:51–58.CrossRefPubMed

23.

Huber S, Medl M, Helbich T, et al. Locally advanced breast carcinoma: computer assisted semiquantitative analysis of color Doppler ultrasonography in the evaluation of tumor response to neoadjuvant chemotherapy (work in progress). J Ultrasound Med 2000; 19:601–607.PubMed

24.

Herholz K, Pietrzyk U, Voges J, et al. Correlation of glucose consumption and tumor cell density in astrocytomas. A stereotactic PET study. J Neurosurg 1993; 79:853–858.PubMed

25.

Donckier V, Van Laethem JL, Goldman S, et al. [F-18] fluorodeoxyglucose positron emission tomography as a tool for early recognition of incomplete tumor destruction after radiofrequency ablation for liver metastases. J Surg Oncol 2003; 84:215–223.CrossRefPubMed

26.

Spaepen K, Stroobants S, Dupont P, et al. [¹⁸F]FDG PET monitoring of tumour response to chemotherapy: does [¹⁸F]FDG uptake correlate with the viable tumour cell fraction? Eur J Nucl Med Mol Imaging 2003; 30:682–688.PubMed

27.

Jacob R, Welkoborsky HJ, Mann WJ, et al. [Fluorine-18]fluorodeoxyglucose positron emission tomography, DNA ploidy and growth fraction in squamous-cell carcinomas of the head and neck. ORL J Otorhinolaryngol Relat Spec 2001; 63:307–313.PubMed

28.

Higashi K, Clavo AC, Wahl RL. Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. J Nucl Med 1993; 34:414–419.PubMed

29.

Buchmann I, Vogg AT, Glatting G, et al. [¹⁸F]5-fluoro-2-deoxyuridine-PET for imaging of malignant tumors and for measuring tissue proliferation. Cancer Biother Radiopharm 2003; 18:327–337.CrossRefPubMed

30.

Okada J, Yoshikawa K, Itami M, et al. Positron emission tomography using fluorine-18-fluorodeoxyglucose in malignant lymphoma: a comparison with proliferative activity. J Nucl Med 1992; 33:325–329.PubMed

31.

Wahl RL, Zasadny K, Helvie M, et al. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 1993; 11:2101–2111.PubMed

32.

Bruce DM, Evans NT, Heys SD, et al. Positron emission tomography: 2-deoxy-2-[¹⁸F]-fluoro-d-glucose uptake in locally advanced breast cancers. Eur J Surg Oncol 1995; 21:280–283.PubMed

33.

Jansson T, Westlin JE, Ahlstrom H, et al. 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.PubMed

34.

Bassa P, Kim EE, Inoue T, et al. Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med 1996; 37:931–938.PubMed

35.

Smith IC, Welch AE, Hutcheon AW, 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; 18:1676–1688.PubMed

36.

Schelling M, Avril N, Nahrig J, et al. Positron emission tomography using [¹⁸F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 2000; 18:1689–1695.PubMed

37.

Tiling R, Linke R, Untch M, et al.¹⁸F-FDG PET and ^99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study. Eur J Nucl Med 2001; 28:711–720.CrossRefPubMed

38.

Mankoff DA, Dunnwald LK, Gralow JR, et al. Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J Nucl Med 2003; 44:1806–1814.PubMed

39.

Mortimer JE, Dehdashti F, Siegel BA, et al. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 2001; 19:2797–2803.PubMed

40.

Burcombe RJ, Makris A, Pittam M, et al. Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [¹⁸F]-fluorodeoxyglucose positron emission tomography. Eur J Cancer 2002; 38:375–379.CrossRefPubMed

41.

Boellaard R, Krak NC, Hoekstra OS, et al. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med 2004 (in press).

42.

Hoekstra CJ, Paglianiti I, Hoekstra OS, et al. Monitoring response to therapy in cancer using [¹⁸F]-2-fluoro-2-deoxy-d-glucose and positron emission tomography: an overview of different analytical methods. Eur J Nucl Med 2000; 27:731–743.CrossRefPubMed

43.

Sokoloff L, Reivich M, Kennedy C, et al. The [¹⁴C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 1977; 28:897–916.PubMed

44.

Reivich M, Kuhl D, Wolf A, Greenberg J, et al. The [¹⁸F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 1979; 44:127–137.PubMed

45.

Huang SC, Phelps ME, Hoffman EJ, et al. Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 1980; 238:E69–E82.PubMed

46.

Phelps ME, Huang SC, Hoffman EJ, et al. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-d-glucose: validation of method. Ann Neurol 1979; 6:371–388.PubMed

47.

Van der Weerdt AP, Klein LJ, Boellaard R, et al. Image-derived input functions for determination of MRGlu in cardiac¹⁸F-FDG PET scans. J Nucl Med 2001; 42:1622–1629.PubMed

48.

Spence AM, Muzi M, Graham MM, et al. Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant. J Nucl Med 1998; 39:440–448.PubMed

49.

Wu HM, Bergsneider M, Glenn TC, et al. Measurement of the global lumped constant for 2-deoxy-2-[¹⁸F]fluoro-d-glucose in normal human brain using [¹⁵O]water and 2-deoxy-2-[¹⁸F]fluoro-d-glucose positron emission tomography imaging. A method with validation based on multiple methodologies. Mol Imaging Biol 2003; 5:32–41.CrossRefPubMed

50.

Graham MM, Muzi M, Spence AM, et al. The FDG lumped constant in normal human brain. J Nucl Med 2002; 43:1157–1166.PubMed

51.

Selberg O, Muller MJ, van den Hoff J, et al. Use of positron emission tomography for the assessment of skeletal muscle glucose metabolism. Nutrition 2002; 18:323–328.CrossRefPubMed

52.

Virtanen KA, Peltoniemi P, Marjamaki P, et al. Human adipose tissue glucose uptake determined using [¹⁸F]-fluoro-deoxy-glucose ([¹⁸F]FDG) and PET in combination with microdialysis. Diabetologia 2001; 44:2171–2179.CrossRefPubMed

53.

Wiggers H, Bottcher M, Nielsen TT, et al. Measurement of myocardial glucose uptake in patients with ischemic cardiomyopathy: application of a new quantitative method using regional tracer kinetic information. J Nucl Med 1999; 40:1292–1300.PubMed

54.

Botker HE, Bottcher M, Schmitz O, et al. Glucose uptake and lumped constant variability in normal human hearts determined with [¹⁸F]fluorodeoxyglucose. J Nucl Cardiol 1997; 4:125–132.PubMed

55.

Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983; 3:1–7.PubMed

56.

Krak NC, van der Hoeven JJ, Hoekstra OS, et al. Measuring [¹⁸F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. Eur J Nucl Med Mol Imaging 2003; 30:674–681.PubMed

57.

Hoekstra CJ, Hoekstra OS, Stroobants SG, et al. Methods to monitor response to chemotherapy in non-small cell lung cancer with¹⁸F-FDG PET. J Nucl Med 2002; 43:1304–1309.

58.

Zasadny KR, Wahl RL. Enhanced FDG-PET tumor imaging with correlation-coefficient filtered influx-constant images. J Nucl Med 1996; 37:371–374.PubMed

59.

Wu HM, Hoh CK, Huang SC, Yao WJ, et al. Quantification of serial tumor glucose metabolism. J Nucl Med 1996; 37:506–513.PubMed

60.

Wu HM, Huang SC, Choi Y, et al. A modeling method to improve quantitation of fluorodeoxyglucose uptake in heterogeneous tumor tissue. J Nucl Med 1995; 36:297–306.PubMed

61.

Kroep JR, Van Groeningen CJ, Cuesta MA, et al. Positron emission tomography using 2-deoxy-2-[¹⁸F]-fluoro-d-glucose for response monitoring in locally advanced gastroesophageal cancer; a comparison of different analytical methods. Mol Imaging Biol 2003; 5:337–346.CrossRefPubMed

62.

Kim CK, Gupta NC, Chandramouli B, et al. Standardized uptake values of FDG: body surface area correction is preferable to body weight correction. J Nucl Med 1994; 35:164–167.PubMed

63.

Schomburg A, Bender H, Reichel C, et al. Standardized uptake values of fluorine-18 fluorodeoxyglucose: the value of different normalization procedures. Eur J Nucl Med 1996; 23:571–574.PubMed

64.

Sugawara Y, Zasadny KR, Neuhoff AW, et al. Reevaluation of the standardized uptake value for FDG: variations with body weight and methods for correction. Radiology 1999; 213:521–525.PubMed

65.

Erselcan T, Turgut B, Dogan D, et al. 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; 29:1630–1638.CrossRefPubMed

66.

Young H, Baum R, Cremerius U, et al. Measurement of clinical and subclinical tumour response using [¹⁸F]-fluoredeoxyglucose and positron emisson tomography: review and 1999 EORTC recommendations. Eur J Cancer 1999; 35:1773–1782.PubMed

67.

Keyes JW Jr. SUV: standard uptake or silly useless value? J Nucl Med 1995; 36:1836–1839.PubMed

68.

Huang SC. Anatomy of SUV. Nucl Med Biol 2000; 27:643–646.PubMed

69.

Hunter GJ, Hamberg LM, Alpert NM, et al. Simplified measurement of deoxyglucose utilization rate. J Nucl Med 1996; 37:950–955.PubMed

70.

Sadato N, Tsuchida T, Nakaumra S, et al. Non-invasive estimation of the net influx constant using the standardized uptake value for quantification of FDG uptake of tumours. Eur J Nucl Med 1998; 25:559–564.CrossRefPubMed

71.

Graham MM, Peterson LM, Hayward RM. Comparison of simplified quantitative analysis of FDG uptake. Nucl Med Biol 2000; 27:647–655.PubMed

72.

Bos R, van Der Hoeven JJ, van Der Wall E, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 2002; 20:379–387.PubMed

73.

Pupa SM, Bufalino R, Invernizzi AM, et al. Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas. J Clin Oncol 1996; 14:85–94.PubMed

74.

Steele RJ, Brown M, Eremin O. Characterisation of macrophages infiltrating human mammary carcinomas. Br J Cancer 1985; 51:135–138.PubMed

75.

Avril N, Rose CA, Schelling M, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol 2000; 18:3495–3502.PubMed

76.

Honkoop AH, Pinedo HM, De Jong JS, et al. Effects of chemotherapy on pathologic and biologic characteristics of locally advanced breast cancer. Am J Clin Pathol 1997; 107:211–218.PubMed

77.

Moll UM, Chumas J. Morphologic effects of neoadjuvant chemotherapy in locally advanced breast cancer. Pathol Res Pract 1997; 193:187–196.

78.

Newman LA, Pernick NL, Adsay V, et al. Histopathologic evidence of tumor regression in the axillary lymph nodes of patients treated with preoperative chemotherapy correlates with breast cancer outcome. Ann Surg Oncol 2003; 10:734–739.CrossRefPubMed

Title: Measuring response to chemotherapy in locally advanced breast cancer: methodological considerations
Authors: Nanda C. Krak
Otto S. Hoekstra
Adriaan A. Lammertsma
Publication date: 01-06-2004
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue Special Issue 1/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-004-1532-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Measuring response to chemotherapy in locally advanced breast cancer: methodological considerations

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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