HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dose Schwarz, J. Articles by Avril, N. Search for Related Content PubMed PubMed Citation Articles by Dose Schwarz, J. Articles by Avril, N.

Early Prediction of Response to Chemotherapy in Metastatic Breast Cancer Using Sequential ¹⁸F-FDG PET

¹ Department of Gynecology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
² Department of Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
³ Division of Nuclear Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
Chemotherapy is currently the treatment of choice for patients with high-risk metastatic breast cancer. Clinical response is determined after several cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures including CT, MRI, plain film radiography, or ultrasound. The aim of this study was to evaluate the use of sequential ¹⁸F-FDG PET to predict response after the first and second cycles of standardized chemotherapy for metastatic breast cancer. Methods: Eleven patients with 26 metastatic lesions underwent 31 ¹⁸F-FDG PET examinations (240–400 MBq of ¹⁸F-FDG; 10-min 2-dimensional emission and transmission scans). Clinical response, as assessed by conventional imaging after completion of chemotherapy, served as the reference. ¹⁸F-FDG PET images after the first and second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients’ blood glucose levels. In addition, whole-body ¹⁸F-FDG PET images were viewed for overall changes in the ¹⁸F-FDG uptake pattern of metastatic lesions within individual patients and compared with conventional imaging results after the third and sixth cycles of chemotherapy. Results: After completion of chemotherapy, 17 metastatic lesions responded, as assessed by conventional imaging procedures. In those lesions, SUV decreased to 72% ± 21% after the first cycle and 54% ± 16% after the second cycle, when compared with the baseline PET scan. In contrast, ¹⁸F-FDG uptake in lesions not responding to chemotherapy (n = 9) declined only to 94% ± 19% after the first cycle and 79% ± 9% after the second cycle. The differences between responding and nonresponding lesions were statistically significant after the first (P = 0.02) and second (P = 0.003) cycles. Visual analysis of ¹⁸F-FDG PET images correctly predicted the response in all patients as early as after the first cycle of chemotherapy. As assessed by ¹⁸F-FDG PET, the overall survival in nonresponders (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). Conclusion: In patients with metastatic breast cancer, sequential ¹⁸F-FDG PET allowed prediction of response to treatment after the first cycle of chemotherapy. The use of ¹⁸F-FDG PET as a surrogate endpoint for monitoring therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.

Key Words: ¹⁸F-FDG • PET • metastases • breast cancer • prediction of response to therapy

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
The treatment of breast cancer patients who have metastatic disease aims to improve survival and quality of life since the disease is generally not curable (1). It is therefore essential to identify patients who do not respond to chemotherapy early in the course of treatment to avoid ineffective therapies and unnecessary side effects such as nausea, vomiting, alopecia, and hematologic toxicity with the risk of subsequent (life-threatening) infections, neurotoxicity (e.g., taxanes), or cardiotoxicity (e.g., anthracyclines). Anatomic imaging procedures including ultrasound, plain film radiography, CT, and MRI are commonly used to follow the size of metastases over time and to determine the degree of response (2). Frequently, several cycles of chemotherapy are necessary to significantly change tumor size and, therefore, current anatomic imaging modalities do not reliably predict therapy response early in the course of treatment (3–7).

PET using ¹⁸F-FDG allows assessment of the metabolic activity of cancer tissue and has been shown to be better than conventional imaging for staging and restaging various types of cancer, including breast cancer (8, 9). PET allows accurate quantification of ¹⁸F-FDG uptake in tissue, and previous studies have demonstrated that standardized uptake values (SUVs) provide highly reproducible parameters of tumor glucose use (10, 11). Several groups have studied the relationship between changes in tumor glucose metabolism and response to treatment in breast cancer (12–17). However, most of these studies used sequential ¹⁸F-FDG PET in patients with locally advanced breast cancer and histopathology after primary (neoadjuvant) chemotherapy served as a reference to assess tumor response. In 1993, Wahl et al. (12) reported 11 women with newly diagnosed locally advanced primary breast cancer undergoing chemohormonotherapy and sequential ¹⁸F-FDG PET. The ¹⁸F-FDG uptake in 8 patients with partial or complete pathologic responses decreased promptly with treatment, whereas the tumor diameter did not significantly decrease. In contrast, 3 patients with nonresponding tumors did not show a significant decrease in ¹⁸F-FDG uptake. So far, there has been little information available on the utility of ¹⁸F-FDG PET for predicting response early in the course of chemotherapy in metastatic breast cancer.

The aim of this study was to prospectively evaluate the use of sequential ¹⁸F-FDG PET in standardized first-line chemotherapy of metastatic breast cancer to predict treatment response early in the course of therapy. Semiquantitative ¹⁸F-FDG PET images after the first and second cycles of chemotherapy were compared with baseline images to determine changes in ¹⁸F-FDG uptake in metastatic tumor lesions. In addition, whole-body ¹⁸F-FDG PET images were viewed for overall changes in the ¹⁸F-FDG uptake pattern of metastatic lesions within individual patients, and the metabolic response was compared with response on conventional imaging after the third and sixth cycles of chemotherapy. Changes in the pattern of ¹⁸F-FDG uptake in metastatic lesions were also compared with overall survival. Clinical response determined by conventional anatomic imaging after completion of chemotherapy served as a reference. The hypothesis was that changes in ¹⁸F-FDG uptake early in the course of treatment allow prediction of the effectiveness of chemotherapy.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
Patients
Patients with the diagnosis of metastatic breast cancer who were participating in a phase III chemotherapy trial were offered enrollment in this prospective evaluation of sequential ¹⁸F-FDG PET. The purpose of the chemotherapy trial was to compare standard chemotherapy using epirubicin/cyclophosphamide with epirubicin/paclitaxel. Inclusion criteria for sequential ¹⁸F-FDG PET were the diagnosis of metastatic breast cancer, at least 1 measurable metastatic lesion seen on conventional anatomic imaging, and an age of 18–70 y. Exclusion criteria were pregnancy, breast feeding, and diabetes mellitus. Between February 1997 and February 2000, 11 patients were enrolled to undergo sequential ¹⁸F-FDG PET for monitoring of treatment response. All patients were treated at the Department of Obstetrics and Gynecology of the University Hospital Hamburg-Eppendorf, Germany (patient characteristics are shown in Table 1). All patients were followed up either until death or until April 2004. The Committee for Human Research at the University Hospital Hamburg-Eppendorf approved the study protocol. A physician explained the details of the study to the patients, and all consented in writing to participate.

Diagnostic Procedures
Patients underwent conventional imaging, including ultrasound, plain film radiography, contrast-enhanced CT, and MRI, depending on the localization of the metastatic lesions. The imaging procedures were performed according to routine clinical practice. Ultrasound was performed by an experienced radiologist, plain film radiographs were obtained in at least 2 projections, and contrast-enhanced CT or MRI was performed if no contraindications were present. A total of 26 separate metastases had been identified before the patients were enrolled in sequential ¹⁸F-FDG PET. The imaging procedures were repeated after 3 cycles of chemotherapy (9 wk), 6 cycles of chemotherapy (18 wk), and 9 cycles of chemotherapy (27 wk).

Classification of Response Seen on Conventional Imaging
Response to treatment was classified according to the criteria of the World Health Organization (2): Complete response was determined as resolution of metastatic lesions; partial response, as a reduction in size (product of the 2 largest perpendicular dimensions) of more than 50%; no change, as a reduction of less than 50% or an increase of less than 25%; and progressive disease, as an increase (product of the 2 largest perpendicular dimensions) of more than 25%. For conventional imaging, patients with no change or with partial or complete response were classified as responders to chemotherapy and patients with progressive disease were classified as nonresponders to chemotherapy.

¹⁸F-FDG PET Imaging
¹⁸F-FDG PET was performed at baseline before chemotherapy, after the first cycle (3 wk) of chemotherapy, and after the second cycle (6 wk) of chemotherapy. Eleven patients underwent a total of 31 ¹⁸F-FDG PET examinations; 2 patients did not undergo a third ¹⁸F-FDG PET examination after the second cycle (6 wk) of chemotherapy. A whole-body PET scanner (ECAT EXACT 47/921; CTI Siemens, Inc.) was used, and patients fasted for at least 6 h before undergoing PET. The serum glucose level was measured before the intravenous administration of 240–400 MBq (approximately 10 mCi) of ¹⁸F-FDG. The blood glucose level in all patients was less than 150 mg/dL. All patients lay supine during the study, after being comfortably positioned on the scanner table with both arms at their sides. Emission scans (2-dimensional) were started 60 min after intravenous administration of ¹⁸F-FDG, with 10 min allowed per bed position. Depending on the location of metastases, emission scans of 1–4 bed positions were acquired, followed by transmission scanning for attenuation correction. Additionally, whole-body emission scans from the base of the skull to the groin were obtained without attenuation correction. Emission data corrected for random events, dead time, and attenuation were reconstructed with filtered backprojection (Hanning filter with cutoff frequency of 0.4 cycles per bin). The image pixel counts were calibrated to activity concentration (Bq/mL) and were decay corrected using the time of tracer injection as a reference. For visual analysis, PET images were printed on transparency films (Helios 810; Sterling Diagnostic Imaging) using a linear gray scale with the highest activity displayed in black. Standard documentation on film included 20 transverse slices with a slice thickness of 13.5 mm, 20 coronal slices with a slice thickness of 13.5 mm, and maximum-intensity projections in anterior, left lateral, right anterior oblique, and left anterior oblique views. In addition, a monitor was used with full control over the display.

PET Image Analysis
The region-of-interest technique was used for quantification of ¹⁸F-FDG uptake in metastatic lesions. Circular regions of interest were placed manually over each lesion by 1 observer. The maximum activity values within the regions of interest were normalized to injected activity and patient body weight and were corrected for variation in blood glucose levels at the time of tracer injection by normalizing to a level of 100 mg/100 mL (SUVs) (18).

An experienced nuclear medicine physician unaware of the patient’s history, clinical findings, and conventional imaging results interpreted the whole-body PET images visually. Response was classified according to the following criteria: Complete response was defined as resolution of abnormal ¹⁸F-FDG uptake in metastatic lesions; partial response, as a reduction in the intensity of uptake or in the number of metastatic lesions with increased uptake; no change, as no change in the number of metastatic lesions and in the intensity of uptake in metastatic lesions; and progressive disease, as an increase in the intensity of uptake or in the number of metastatic lesions. Patients with ¹⁸F-FDG PET scans showing partial or complete response were classified as responders to chemotherapy, and patients with scans showing no change or progressive disease were classified as nonresponders.

Statistical Analysis
The Mann–Whitney U test was used to compare SUVs between responding and nonresponding metastases at a 5% level of significance.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
Conventional Imaging
Conventional imaging was repeated after the third, sixth, and ninth cycles of chemotherapy and compared with the pretreatment findings. Table 2 shows the treatment response for individual metastases after the third and sixth cycles of chemotherapy. Two of 11 patients had a mixed response, with metastases classified as no change and partial response. After the third cycle of chemotherapy, 9 patients were classified as responders (1, complete response; 5, partial response; and 3, no change) and 2 patients as nonresponders (progressive disease). In accord with the protocol of the chemotherapy trial, the 2 patients who did not respond were excluded from further participation in the study. The findings on conventional imaging changed after the sixth cycle of chemotherapy; only 6 patients were classified as responders and another 3 patients as nonresponders (Table 3). A patient with a lung metastasis (patient 8) initially responded after the third cycle (partial response), but the metastasis progressed in size after the sixth cycle of chemotherapy (progressive disease). There was no change between the sixth and ninth cycles of chemotherapy, and responders who continued to receive chemotherapy were still classified as responders after the ninth cycle of chemotherapy. In summary, 6 of 11 patients were classified as responders and 5 patients as nonresponders on the basis of conventional imaging results after completion of chemotherapy, which determined the gold standard for this study. Therefore, conventional imaging after the third cycle of chemotherapy misclassified 3 patients (27%) as responders (Table 3).

View larger version (12K): [in this window] [in a new window]   FIGURE 1. Changes in SUV in responding and nonresponding metastases.

Patient Follow-up and Survival
Mean follow-up was 14.5 mo (range, 2–39 mo). During this time, 10 patients died and mean overall survival was 14.5 ± 3.6 mo. The overall survival in nonresponders identified by ¹⁸F-FDG PET after the first cycle of chemotherapy was 8.8 ± 6.7 mo, compared with 19.2 ± 13.6 mo in responders (not significant).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
This study demonstrated that in patients with metastatic breast cancer, sequential ¹⁸F-FDG PET allowed prediction of response early in the course of chemotherapy. Changes in tumor ¹⁸F-FDG SUVs were statistically significantly different between responding and nonresponding metastatic lesions after the first (P = 0.02) and second (P = 0.003) cycles of chemotherapy. Most studies that addressed the role of sequential ¹⁸F-FDG PET for predicting response to chemotherapy included patients with locally advanced breast cancer before surgery (15–17). Schelling et al. (16) compared changes in ¹⁸F-FDG uptake with pathologic response using distinct histopathologic criteria, namely minimal residual disease and gross residual disease. By a threshold defined as a decrease of >55% compared with baseline, all responders were correctly identified after the first cycle of chemotherapy. The accuracy of predicting histopathologic response was 88% and 91% after the first and second cycles of therapy, respectively. In another study, 30 patients with locally advanced breast cancer received 8 doses of primary chemotherapy (15). The mean reduction in ¹⁸F-FDG uptake after the first cycle of chemotherapy was significantly higher in responding than in nonresponding tumors. Little information is available on the clinical utility of sequential ¹⁸F-FDG PET in patients with metastatic breast cancer. Jansson et al. (13) studied 16 patients with advanced breast cancer who underwent polychemotherapy and found decreased ¹⁸F-FDG uptake 6–13 d after the first cycle of chemotherapy in 8 of 12 patients who had responded to chemotherapy. Stafford et al. recently reported a close correlation between changes in ¹⁸F-FDG uptake and the overall clinical assessment of response in 24 breast cancer patients with bone metastases (19). However, more information is needed on how these findings and the ¹⁸F-FDG PET results from the neoadjuvant treatment discussed above could potentially be used in the clinical setting to predict response to chemotherapy in metastatic breast cancer.

Our study confirms previous reports on the predictive information of early changes in glucose metabolism after initiation of chemotherapy (5, 7, 15, 17). When compared with the baseline ¹⁸F-FDG PET scan, the SUV in responding metastatic lesions decreased to 72% ± 21% after the first cycle of chemotherapy and to 54% ± 16% after the second cycle. In contrast, ¹⁸F-FDG uptake in metastases not responding to chemotherapy declined only to 94% ± 19% after the first cycle and 79% ± 9% after the second cycle. Gennari et al. also found a rapid and significant decrease in tumor glucose metabolism after the first cycle of chemotherapy in 6 of 9 responders and no significant decrease in nonresponders (20). Modern treatment regimens in metastatic breast cancer are developing toward being tailored to the needs of each patient. Response to therapy in solid tumors is currently assessed by measuring the change in tumor size (2)—a method that often is not accurate early in the course of chemotherapy. It is becoming increasingly important to identify response to therapy as early as possible so that ineffective therapies can be discontinued. Particularly, early identification of nonresponders is crucial to avoid ineffective treatment, unnecessary side effects, and costs (16). Patients not responding to continued chemotherapy experience a decreased quality of life and are detained from potentially more effective treatments. Dissolution and shrinkage of a tumor is the final step in a complex cascade of cellular and subcellular alterations after chemotherapy. Therefore, changes in the cellular energy metabolism assessed by ¹⁸F-FDG PET are more likely to predict response than are changes in tumor size (3, 5–7).

In this series, whole-body ¹⁸F-FDG PET correctly predicted the response in all patients as early as after the first cycle (3 wk) of chemotherapy. Conventional imaging performed after the third cycle (9 wk) of chemotherapy misclassified 3 patients (27%) falsely as responders and was less accurate than ¹⁸F-FDG PET. Chemotherapy is usually ineffective and discontinued in patients with progressive disease (21). A specific dilemma is presented by no change on conventional imaging, specifically in the first assessment after 3 cycles of chemotherapy. Chemotherapy is frequently continued in these patients since they might still respond later in the course of treatment. In our study, 3 patients who had no change on conventional imaging after the third cycle of chemotherapy had been correctly classified by ¹⁸F-FDG PET after the first cycle of chemotherapy. A specific strength of ¹⁸F-FDG PET is the identification of nonresponders, who are characterized by virtually no change in ¹⁸F-FDG uptake after initiation of chemotherapy. The overall survival in the 5 patients who did not respond, according to ¹⁸F-FDG PET, was 8.8 ± 6.7 mo, compared with 19.2 ± 13.6 mo in responding patients. ¹⁸F-FDG PET identified 2 nonresponders 3 wk (1 cycle of chemotherapy) and 3 nonresponders 12 wk (4 cycles of chemotherapy) before progression was detected on conventional imaging. Use of a PET-based strategy could have avoided 14 cycles of chemotherapy in these 5 patients, and they could have received earlier second-line chemotherapy. In our study, 2 of 11 patients had a mixed response. An advantage of ¹⁸F-FDG PET is that it can more easily identify a mixed response than can conventional imaging, which frequently is used to assess 1 "leading lesion" for changes in size. Another advantage of ¹⁸F-FDG PET is the ability to monitor lesions in soft tissue, lymph nodes, liver, lungs, and bone in 1 imaging procedure that might be more cost effective than various imaging modalities currently used.

Our study had several limitations. Because of the small number of patients studied, a quantitative (SUV) analysis on a patient basis was not possible. The statistical analysis of changes in ¹⁸F-FDG uptake in individual metastases was based on the assumption that they are independent, which might not be true in metastases within the same patient. On the other hand, our results were consistent with previous findings for locally advanced breast cancer and other tumor types (5, 7, 12, 15–17). An important advantage of the study design was that all patients underwent standardized chemotherapy and that follow-up information was available for a mean of 14.5 mo.

In the present study, ¹⁸F-FDG PET was not used to change patient management; nevertheless, the question arises of how to use ¹⁸F-FDG PET in the clinical setting. In the United States, health insurers reimburse the cost of ¹⁸F-FDG PET as an adjunct to standard imaging for monitoring treatment response in women with locally advanced, metastatic breast cancer when a change in therapy is anticipated. However, specific criteria to determine response by ¹⁸F-FDG PET have yet to be established. If semiquantitative analysis is used, close monitoring of all factors that affect SUV measurements is crucial, such as the amount of activity injected, the uptake time before imaging, and the scanner cross calibration (18). The threshold for differentiating between responders and nonresponders on the basis of changes in ¹⁸F-FDG uptake is critical. Chemotherapy should not be discontinued in responders, even at the cost of not identifying all nonresponders. Weber et al. recently proposed that metabolic response be defined as an SUV decrease larger than 2 times the SD (20%) of spontaneous changes in ¹⁸F-FDG uptake (5, 11). In the present study, a decrease in ¹⁸F-FDG SUV of more than 20%, compared with baseline, after the first cycle of chemotherapy correctly identified 5 (71.2%) of 7 nonresponding and 12 (85.7%) of 14 responding lesions. The proposed approach is supported by a recent study on non–small cell lung cancer in which this criterion was prospectively applied to 57 patients with advanced disease and only 1 of 27 metabolic nonresponders achieved a partial response after completion of chemotherapy, resulting in a negative predictive value of 96% (5). However, this promising strategy needs to be validated in a separate prospective study for patients with metastatic breast cancer.

	CONCLUSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
In patients with metastatic breast cancer, the effectiveness of chemotherapy can be evaluated earlier with ¹⁸F-FDG PET than with conventional imaging. Sequential ¹⁸F-FDG PET performed at baseline and after initiation of treatment allowed prediction of response as early as after the first cycle of chemotherapy. Furthermore, ¹⁸F-FDG PET allows monitoring of multiple metastases using a single functional imaging procedure. The use of a 20% decrease in SUV after the first cycle of chemotherapy as a threshold for identifying nonresponders needs further evaluation in a larger prospective study. The use of ¹⁸F-FDG PET findings as a surrogate endpoint for predicting therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.

	ACKNOWLEDGMENTS

 
We thank Dr. H.-J. Lueck, AGO German Breast Study Group, for helpful cooperation. This study was supported by Deutsche Krebshilfe (Mildred Scheel Stiftung).

	FOOTNOTES

 
Received Aug. 11, 2004; revision accepted Mar. 23, 2005.

For correspondence or reprints contact: Joerg Dose Schwarz, MD, Department of Gynecology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.

E-mail: dose{at}uke.uni-hamburg.de

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 

1. Ligibel JA, Winer EP. Trastuzumab/chemotherapy combinations in metastatic breast cancer. Semin Oncol. 2002;29:38–43.
2. Therasse P, Arbuck SG, Eisenhauer EA, 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;92:205–216.[Abstract/Free Full Text]
3. Weber WA, Ott K, Becker K, et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol. 2001;19:3058–3065.[Abstract/Free Full Text]
4. Spaepen K, Stroobants S, Dupont P, et al. Early restaging positron emission tomography with (18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2002;13:1356–1363.[Abstract/Free Full Text]
5. Weber WA, Petersen V, Schmidt B, 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;21:2651–2657.[Abstract/Free Full Text]
6. Ott K, Fink U, Becker K, et al. Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J Clin Oncol. 2003;21:4604–4610.[Abstract/Free Full Text]
7. Wieder H, Brucher BL, Zimmerman F, et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol. 2004;22:900–909.[Abstract/Free Full Text]
8. Rose C, Dose J, Avril N. Positron emission tomography for the diagnosis of breast cancer. Nucl Med Commun. 2002;23:613–618.[Medline]
9. Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology. 2004;231:305–332.[Abstract/Free Full Text]
10. 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;196:167–173.[Abstract/Free Full Text]
11. Weber WA, Ziegler SI, Thodtmann R, Hanauske AR, Schwaiger M. Reproducibility of metabolic measurements in malignant tumors using FDG PET. J Nucl Med. 1999;40:1771–1777.[Abstract/Free Full Text]
12. 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;11:2101–2111.[Abstract/Free Full Text]
13. 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.[Abstract]
14. Dehdashti F, Flanagan FL, Mortimer JE, Katzenellenbogen JA, Welch MJ, Siegel BA. Positron emission tomographic assessment of "metabolic flare" to predict response of metastatic breast cancer to antiestrogen therapy. Eur J Nucl Med. 1999;26:51–56.[Medline]
15. Smith IC, Welch AE, Hutcheon AW, et al. Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol. 2000;18:1676–1688.[Abstract/Free Full Text]
16. Schelling M, Avril N, Nährig J, et al. Positron emission tomography using [F-18]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol. 2000;18:1689–1695.[Abstract/Free Full Text]
17. 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.[Abstract/Free Full Text]
18. Avril N, Bense S, Ziegler SI, et al. Breast imaging with fluorine-18-FDG PET: quantitative image analysis. J Nucl Med. 1997;38:1186–1191.[Abstract/Free Full Text]
19. Stafford SE, Gralow JR, Schubert EK, et al. Use of serial FDG PET to measure the response of bone-dominant breast cancer to therapy. Acad Radiol. 2002;9:913–921.[Medline]
20. Gennari A, Donati S, Salvadori B, et al. Role of 2-[¹⁸F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients. Clin Breast Cancer. 2000;1:156–161.[Medline]
21. Mincey BA, Perez EA. Advances in screening, diagnosis, and treatment of breast cancer. Mayo Clin Proc. 2004;79:810–816.[Medline]

This article has been cited by other articles:

				U. Tateishi, C. Gamez, S. Dawood, H. W. D. Yeung, M. Cristofanilli, and H. A. Macapinlac Bone Metastases in Patients with Metastatic Breast Cancer: Morphologic and Metabolic Monitoring of Response to Systemic Therapy with Integrated PET/CT Radiology, April 1, 2008; 247(1): 189 - 196. [Abstract] [Full Text] [PDF]

				N. C. Hodgson and K. Y. Gulenchyn Is There a Role for Positron Emission Tomography in Breast Cancer Staging? J. Clin. Oncol., February 10, 2008; 26(5): 712 - 720. [Abstract] [Full Text] [PDF]

				D. S. Boss, R. V. Olmos, M. Sinaasappel, J. H. Beijnen, and J. H. M. Schellens Application of PET/CT in the Development of Novel Anticancer Drugs Oncologist, January 1, 2008; 13(1): 25 - 38. [Abstract] [Full Text] [PDF]

				A. L. Kesner, W.-A. Hsueh, N. L. Htet, B. S. Pio, J. Czernin, M. D. Pegram, M. E. Phelps, and D. H.S. Silverman Biodistribution and Predictive Value of 18F-Fluorocyclophosphamide in Mice Bearing Human Breast Cancer Xenografts J. Nucl. Med., December 1, 2007; 48(12): 2021 - 2027. [Abstract] [Full Text] [PDF]

				E. L. Rosen, W. B. Eubank, and D. A. Mankoff FDG PET, PET/CT, and Breast Cancer Imaging RadioGraphics, October 1, 2007; 27(suppl_1): S215 - S229. [Abstract] [Full Text] [PDF]

				R. J. Francis, M. J. Byrne, A. A. van der Schaaf, J. A. Boucek, A. K. Nowak, M. Phillips, R. Price, A. P. Patrikeos, A. W. Musk, and M. J. Millward Early Prediction of Response to Chemotherapy and Survival in Malignant Pleural Mesothelioma Using a Novel Semiautomated 3-Dimensional Volume-Based Analysis of Serial 18F-FDG PET Scans J. Nucl. Med., September 1, 2007; 48(9): 1449 - 1458. [Abstract] [Full Text] [PDF]

				F.-M. S. Kong, K. A. Frey, L. E. Quint, R. K. T. Haken, J. A. Hayman, M. Kessler, I. J. Chetty, D. Normolle, A. Eisbruch, and T. S. Lawrence A Pilot Study of [18F]Fluorodeoxyglucose Positron Emission Tomography Scans During and After Radiation-Based Therapy in Patients With Non Small-Cell Lung Cancer J. Clin. Oncol., July 20, 2007; 25(21): 3116 - 3123. [Abstract] [Full Text] [PDF]

				R. L. Ehman, W. R. Hendee, M. J. Welch, N. R. Dunnick, L. B. Bresolin, R. L. Arenson, S. Baum, H. Hricak, and J. H. Thrall Blueprint for Imaging in Biomedical Research Radiology, July 1, 2007; 244(1): 12 - 27. [Full Text] [PDF]

				C. Nahmias, W. T. Hanna, L. M. Wahl, M. J. Long, K. F. Hubner, and D. W. Townsend Time Course of Early Response to Chemotherapy in Non-Small Cell Lung Cancer Patients with 18F-FDG PET/CT J. Nucl. Med., May 1, 2007; 48(5): 744 - 751. [Abstract] [Full Text] [PDF]

				H. Kuehl, P. Veit, S. J. Rosenbaum, A. Bockisch, and G. Antoch Can PET/CT Replace Separate Diagnostic CT for Cancer Imaging? Optimizing CT Protocols for Imaging Cancers of the Chest and Abdomen J. Nucl. Med., January 1, 2007; 48(1_suppl): 45S - 57S. [Abstract] [Full Text] [PDF]

				W.-A. Hsueh, A. L. Kesner, A. Gangloff, M. D. Pegram, M. Beryt, J. Czernin, M. E. Phelps, and D. H.S. Silverman Predicting Chemotherapy Response to Paclitaxel with 18F-Fluoropaclitaxel and PET J. Nucl. Med., December 1, 2006; 47(12): 1995 - 1999. [Abstract] [Full Text] [PDF]

				O. Couturier, G. Jerusalem, J.-M. N'Guyen, and R. Hustinx Sequential Positron Emission Tomography Using [18F]Fluorodeoxyglucose for Monitoring Response to Chemotherapy in Metastatic Breast Cancer. Clin. Cancer Res., November 1, 2006; 12(21): 6437 - 6443. [Abstract] [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dose Schwarz, J. Articles by Avril, N. Search for Related Content PubMed PubMed Citation Articles by Dose Schwarz, J. Articles by Avril, N.