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Journal of Clinical Oncology, Vol 25, No 21 (July 20), 2007: pp. 3116-3123 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.10.3747 A Pilot Study of [18F]Fluorodeoxyglucose Positron Emission Tomography Scans During and After Radiation-Based Therapy in Patients With Non–Small-Cell Lung Cancer
From the Departments of Radiation Oncology and Radiology (Nuclear Medicine and Thoracic Radiology), University of Michigan; and Radiation Oncology, Veterans Affairs Health Center, Ann Arbor, MI Address reprint requests to Feng-Ming Spring Kong, MD, PhD, MPH, University of Michigan, Department of Radiation Oncology, UH-B2C490, Box 0010, 1500 E Medical Center Dr, Ann Arbor, MI 48109; e-mail: Fengkong{at}med.umich.edu
Purpose: To study whether changes of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) during treatment correlate with post-treatment responses in tumor and normal lung in patients with non–small-cell lung cancer (NSCLC). Patients and Methods: Patients with stage I to III NSCLC requiring a definitive dose of fractionated radiation therapy (RT) were eligible. FDG-PET/computed tomography scans were acquired before, during, and after RT. Tumor and lung metabolic responses were assessed qualitatively by physicians and quantitatively by normalized peak FDG activity (the ratio of the maximum FDG activity divided by the mean of the aortic arch background). Results: The study reached the goal of recruiting 15 patients between February 2004 and August 2005. Of these, 11 patients had partial metabolic response, two patients had complete metabolic response, and two patients had stable disease at approximately 45 Gy during RT. The mean peak tumor FDG activity was 5.2 (95% CI, 4.0 to 6.4), 2.5 (95% CI, 2.0 to 3.0), and 1.7 (95% CI, 1.3 to 2.0) on pre-, during, and post-RT scans, respectively. None of the patients had appreciable changes in the lung during RT. The peak FDG activity of the lung was 0.47 (95% CI, 0.36 to 0.59), 0.52 (95% CI, 0.40 to 0.64), and 1.29 (95% CI, 0.82 to 1.76), on pre-, during-, and post-RT scans, respectively. The qualitative response during RT correlated with the overall response post-RT (P = .03); the peak tumor FDG activity during RT correlated with those 3 months post-RT (R2 = 0.7; P < .001). Conclusion: This pilot study suggests a significant correlation in tumor metabolic response and no association in lung FDG activity between during RT scans and 3 months post-RT scans in patients with NSCLC. Additional study with a large number of patients is needed to validate these findings.
The current treatment outcome remains poor for patients with lung cancer. In 2006, the ratio of deaths divided by the number of new patients was estimated to be 93% in the United States,1 with 85% of these patients expected to have non–small-cell lung cancers (NSCLCs). Despite the advances in the field and the depth of knowledge regarding the treatment response of lung cancers, implementation of individualized therapy is handicapped by the lack of knowledge about whether a patient has responded to a given therapy until the treatment has been completed. A tumor functional imaging tool2 such as [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) has been used to stage and monitor tumor response after completion of preoperative or definitive chemoradiotherapy in patients with NSCLC.3-15 It has been shown that the magnitude in changes of the FDG uptake in tumors correlated with pathologic response5-6,8-10 and overall survival.4,7,11,14 A return of the standard uptake value (SUV) to normal levels after treatment seems to be a marker of complete tumor response and a sensitive indicator of good prognosis.4,7 Researchers from Australia have also demonstrated that a post-treatment PET response correlated with the treatment failure pattern,4 and was a better predictor of survival outcome than computed tomography (CT) response, stage, or pretreatment performance status.7 FDG-PET is thus suitable for therapy monitoring in patients with NSCLC. FDG-PET scans for treatment response usually are performed at least 6 to 8 weeks or longer after radiation therapy (RT) and 2 weeks after chemotherapy; this practice might have contributed to the consensus recommendations in National Cancer Institute Trials.16 This consensus is partially due to a speculated confounding FDG uptake from treatment-induced inflammation. However, a PET scan performed after completion of treatment has limited applicability in clinical practice because it provides no opportunity to shape the first-line treatment regimen. It is unclear if FDG-PET scans performed during the course of fractionated RT can assess tumor metabolic response without confounding effect from adjacent normal tissue. The goal of this study was to obtain a FDG-PET/CT scan at approximately 45 Gy during RT and correlate the response with the overall response. Specifically, we hypothesized that tumor FDG activity decreases during RT, there is no significant confounding FDG activity in the irradiated lung during RT, and changes in tumor FDG activity during RT correlate with ultimate response after completion of the treatment.
Study Population This was an Institutional Review Board–approved prospective pilot study. Eligible patients included those with stage I to III NSCLC who required a definitive course of fractionated three-dimensional conformal RT with or without chemotherapy. Patients with stage I or II disease were administered conventionally fractionated (2.0 to 2.1-Gy daily fractions); patients with stage III disease were treated with concurrent and adjuvant carboplatin and paclitaxel under a prospective clinical trial, in which patients may receive higher doses than in common practice. The dose of RT for the protocol patients was based on an estimated normal lung complication probability of 15%, with radiation fraction size ranging from 2.2 to 3.4 Gy delivered within 30 daily fractions. Patients with prior thoracic RT were excluded from the study. The mean duration of RT course was 45 days (95% CI, 42 to 50 days).
Study Design The FDG-PET/CT scan was performed in a standard fashion on a flat table top using a hybrid PET/CT scanner (Biograph Classic; Siemens Medical Solutions, Hoffman Estates, IL), with patients’ arms raised above the head in the treatment position. The CT images (5-mm slices) for the PET/CT study typically were obtained during quiet ventilation. Emission PET images were obtained beginning 60 minutes after administration of 8 to 10 mCi of [18F]FDG. For the PET scan, the blood glucose level was required to be less than 150 mg/mL. The PET scans were evaluated qualitatively for tumor and lung response by both a nuclear medicine radiologist (K.A.F.) and a radiation oncologist (F.M.K.), and by objective quantification of FDG uptake in regions of interest (ROI). SUV estimation was performed using e.soft express (version 3.5; Siemens Medical Solutions). Peak activities in primary tumors, nodes, and lungs were determined relative to the mean intravascular background in the aortic arch. Given that SUV varies with many factors, such as the exact amount of radioactive tracer administrated, the interval between tracer injection and the scanning time, the blood glucose level, and so on, we used normalized SUV (NSUV) to measure the FDG activity of each ROI (such as primary tumor, involved node, or lung) to improve the reproducibility of this measure. NSUV was calculated as using the following equation: NSUV = peak SUV of ROI/mean SUV of the aortic arch. The peak activity was chosen for the tumor because it is the most reproducible measurement and a commonly used parameter in assessing tumor activity in practice. The mean value is more representative of the activity of mediastinal background in the aortic arch where clear borders can often be identified in a reproducible manner. The FDG uptake in irradiated lung was first assessed semiquantitatively based on a grading system modified from Hicks et al.15 The peak FDG activity also was determined in a lung region adjacent to but not abutting the tumor. The area with the greatest intensity in the lung was selected as the ROI of irradiated lung. To estimate the tumor volume, each PET/CT data set was transferred to an in-house planning system (University of Michigan plan), and registered to its corresponding simulation CT data set, which was acquired with intravenous contrast. The CT portion of the PET/CT scan (which was obtained without intravenous contrast) was used for registration with the treatment planning CT scan and for anatomic assessment of tumor change. The gross tumor volume (GTV) on CT scan (CT-GTV) was contoured in a standard fashion using the lung window setting for lung borders and mediastinal window setting for borders connecting to mediastinum.
Study End Points and Data Analysis
Patient Characteristics This pilot study completed its accrual goal of 15 patients between February 2004 and August 2005. The minimum follow-up was 16 months for 10 patients who were still alive during the last follow-up. The patient characteristics and clinical outcomes are summarized in Appendix Table A1 (online only). The pre-RT and during RT scans were obtained at 8.5 days (95% CI, 6 to 11 days) before and 29 days (95% CI, 28 to 31 days) after start of RT, respectively. The post-RT scans were obtained at 94 days (95% CI, 83 to 105 days) after completion of RT and were at least 1 month after the last dose of adjuvant chemotherapy.
Tumor Metabolic Responses and FDG Activity During RT and Post-RT
All of the FDG-avid primary tumors had a reduction in peak FDG activity, whereas the non–FDG-avid tumor changed minimally during RT (Fig 3). The mean NSUV of the primary tumors for all 15 patients was 5.2 (95% CI, 4.0 to 6.4) pre-RT, and decreased to 2.5 (95% CI, 2.0 to 3.0) during RT and 1.7 (95% CI, 1.3 to 2.0) post-RT. The differences in the mean tumor peak activity between scans obtained at the various time points were statistically significant (during RT v pre-RT, P = .001; post-RT v pre-RT, P < .001; post-RT v during RT, P = .002). There were remarkable individual differences regarding the rate of reduction among the primary tumors during RT and post-RT  (Fig 5).
The FDG activity of metastatic lymph nodes also decreased during RT (Fig 4). Of eight nodal lesions, four reached CMR during RT, and all of the CMR nodal lesions remained CMR 3 months after completion of RT and during the last follow-up. The mean NSUV of nodal diseases decreased from 2.0 (95% CI, 1.5 to 0.6) to 1.0 (95% CI, 0.8 to 1.2; P = .006) after approximately 45 Gy of RT was delivered. There was no significant difference in NSUV of nodes between during RT and post-RT scans. The heterogeneity of changes was also seen in the patients with nodal disease (Fig 6).
Lung FDG Activity During RT and Post-RT Table 3 lists radiation-induced changes in the lung in all patients on during RT and post-RT PET scans and post-RT CT scans.15 For the during RT scans, none of 15 patients showed radiation-induced grade  2 elevations (Fig 7 for grading examples) lung FDG activity, whereas six of 13 post-RT scans had grade 2 lung activity (P = .009).
The mean lung NSUV was 0.47 (95% CI, 0.36 to 0.59), 0.52 (95% CI, 0.40 to 0.64), and 1.29 (95% CI, 0.82 to 1.76), on pre-RT, during RT, and post-RT scans, respectively (Fig 8). There were no significant differences in peak FDG activity within irradiated lung between pre-RT and during RT scans (P = .34). The FDG activity within irradiated lung was significantly higher on the post-RT scans (P = .01). None (0%) of the 15 patients versus six (46%) of 13 patients had the lung peak NSUV elevated above the aortic arch background on the during RT and post-RT scan, respectively. In addition, radiation-induced elevation in lung FDG activity on the post-RT scan was associated significantly with severe interstitial changes on the post-RT CT scans (Table 3; P = .04). Three of six patients (50%) with grade 2 radiation-induced lung changes versus none of the remaining group (zero of nine patients) had clinical grade 2 or above pneumonitis.
Correlation Between Tumor Responses During RT and Post-RT There was a significant association for CMR or noncomplete metabolic responses between during- and post-RT PET scans, with a Cohen's  coefficient of 0.625 (P = .03). Tumor CMR was concordant with during- and post-RT scans in 10 of 12 patients (Table 2). The NSUV reduction of primary tumors and nodes obtained from the during RT scans correlated significantly with that of the post-RT PET scans (Fig 9A for primary tumors, P < .0001; Fig 9B for metastatic nodes, P = .01). Post-RT NSUV reduction (percent to the pre-RT NSUV) was also correlated inversely with NSUV pre-RT (R2 = 0.55; P = .003).
The metabolic response during RT was associated significantly with CT responses on post-RT scan (Table 2; test P = .03). There was no significant difference between reduction (mean, 60%; 95% CI, 48% to 71%) in FDG activity and CT-GTV on the post-RT scans (mean, 50%; 95% CI, 32% to 68%; P = .32).
This pilot study has shown a significant reduction of tumor FDG activity in patients with NSCLC without a significant confounding effect in the irradiated lung during fractionated RT. Tumor metabolic response and the peak tumor FDG activity at approximately 45 Gy during RT vary from patient to patient and are highly correlated with the ultimate responses 3 to 4 months after completion of RT. The results are intriguing in that radiation induced a significant reduction in FDG activity during the course of treatment in patients with NSCLC. Studies have shown that FDG activity after the first cycle of chemotherapy was predictive of tumor control and overall survival in several other cancers such as breast cancer,18 gastroesophageal cancer,19 lymphoma,20 and head and neck cancer.21 The head and neck cancer study included obtaining an FDG-PET during RT (after 16 to 35 Gy) and reported a significant association of metabolic response between during RT PET scans and 5 to 6 weeks post-treatment response. In patients with NSCLC, researchers have demonstrated that post-RT metabolic response is highly associated with tumor control and overall survival.4,12,14,15 Mac Manus et al7 reported that post-RT metabolic response predicted overall survival better than CT responses or other clinical factors. Although there were not enough patients to perform survival analyses in this study, a significant association of metabolic response and peak FDG activity between during RT and post-RT scans suggests a potential of using the during RT PET response (at approximately 45 Gy) to predict long-term survival in lung cancer. Future studies with larger numbers of patients are needed to confirm such a finding and determine if FDG activity during RT might provide an opportunity (in a subsequent study) to individualize treatment by adjusting radiation intensity or altering the treatment regimen for the remaining treatments, based on the observed tumor responsiveness. The best timing to obtain the during RT PET scan is unclear. The FDG-PET activity tends to show an initial increase followed by a constant decline after treatment.22,23 In one patient from this study, an additional PET scan was performed at 15 Gy; this showed an increase in peak FDG activity, indicating a progression of metabolic active disease based on assessment by the physician, whereas this patient had a 86% FDG activity reduction at approximately 45 Gy and 94% at 4 months post-RT. The biologic mechanism is also unknown. Animal studies on image and pathology correlations are ongoing at our institution. Early elevation of FDG activity may be associated with acute inflammation in the normal tissue or elevated metabolic activity within the tumor cells; the later reduction in FDG uptake is a reflection of reduction in viable tumor cells or reduction of tumor activity. Given that tumor FDG activity from the first and second weeks of fractionated RT were quite noisy,24 and results from the fourth to fifth week in this study showed a significant association with post-RT response, we recommend during RT FDG-PET be performed at about 4 weeks within a 6- to 7-week course of definitive RT. The confounding effect in the surrounding lung is a major concern in current practice if a FDG-PET/CT scan is acquired during the course of treatment. For the first time to our knowledge, this study has demonstrated that radiation-induced elevation of FDG activity in the lung did not occur until months after completion of RT (Fig 2; Table 3), although significant elevation was seen in the esophagus during RT (unpublished data from our group). Noticeable increases of FDG uptake were seen in lung after completion of RT in only 46% (six of 13) of patients, and such changes were associated with clinical pneumonitis. These findings disprove the traditional belief that radiation causes inflammatory changes in normal lung tissue during RT, and support the biologic concept of the lung as a type of slow-reacting tissue (compared with esophagus, which is an early-reacting tissue) in the response to radiation. The delayed radiation-induced elevation in FDG activity in the lung demonstrates the appropriateness of obtaining a FDG-PET/CT scan during RT as an effective tool for identifying the target for individualized adaptive therapy. In addition to using PET scans during RT to predict long-term survival outcome, the close correlation of metabolic responses between during RT and post-RT scans also provides motivation for future clinical trials to alter the treatment regimen or to escalate the radiation dose for the remaining part of RT in those patients who are predicted to be poor responders during RT. In a radiation planning study using FDG-avid tumor acquired during RT as the target for adaptive boost radiation after approximately 45 Gy, we were able to escalate the dose of radiation to more active tumors by a median of 40% while keeping the minimum dose of primary tumor more than the standard prescription and maintaining the normal tissue complication probability of the lung unchanged.25 Given that higher dose radiation is associated with improved survival,26 such a strategy may have the potential to improve long-term outcome in patients with NSCLC. A clinical trial is planned currently at our institution to explore this hypothesis further. Although the results are promising, one must be cautioned that this study is limited by the small number of patients, inclusion of a heterogeneous study population, and nonuniform treatment regimens. The study was designed as a prospective pilot trial, and significant P values would only be associated with effects that are relatively large in magnitude; in addition, as is true in studies that are not designed to demonstrate noninferiority, nonsignificant P values should not be interpreted as proof of no effect. In summary, this pilot study suggests that tumor metabolic response during the course of RT correlates with tumor metabolic and density response 3 to 4 months after the completion of RT. An FDG-PET/CT scan during RT may be more appropriate than the post-RT scan due to reduced confounding effect from the adjacent lung. Studies with a larger number of patients and with uniform regimens of treatment are needed to validate this promising finding and to determine if a FDG-PET/CT scan during the later portion of RT should be performed as a standard practice to adapt the remaining treatment and improve individual patient outcomes.
The author(s) indicated no potential conflicts of interest.
Conception and design: Feng-Ming Spring Kong, Kirk A. Frey, Randall K. Ten Haken, James A. Hayman, Daniel Normolle, Avraham Eisbruch, Theodore S. Lawrence Financial support: Feng-Ming Spring Kong, Avraham Eisbruch, Theodore S. Lawrence Administrative support: Feng-Ming Spring Kong, Kirk A. Frey, Randall K. Ten Haken, James A. Hayman, Indrin J. Chetty, Daniel Normolle, Avraham Eisbruch, Theodore S. Lawrence Provision of study materials or patients: Feng-Ming Spring Kong, Kirk A. Frey, Leslie E. Quint, Marc Kessler, James A. Hayman, Avraham Eisbruch Collection and assembly of data: Feng-Ming Spring Kong, Kirk A. Frey, Leslie E. Quint, Randall K. Ten Haken, Marc Kessler, Indrin J. Chetty Data analysis and interpretation: Feng-Ming Spring Kong, Kirk A. Frey, Randall K. Ten Haken, Theodore S. Lawrence Manuscript writing: Feng-Ming Spring Kong, Kirk A. Frey, Randall K. Ten Haken, Marc Kessler, James A. Hayman, Indrin J. Chetty, Avraham Eisbruch, Theodore S. Lawrence Final approval of manuscript: Feng-Ming Spring Kong, Kirk A. Frey, Leslie E. Quint, Randall K. Ten Haken, Marc Kessler, James A. Hayman, Indrin J. Chetty, Daniel Normolle, Avraham Eisbruch, Theodore S. Lawrence Other: Theodore S. Lawrence [Mentor of the ASCO Young Investigator award]
We thank Lujun Zhao, MD, Mary Feng, MD, Shaneli Fernando, MD, and Daniel Tatro, MD, for image analysis/registration and tumor delineations; and Benedict Fraass, PhD, Gregory P. Kalemkerian, MD, Doug Arenberg, MD, Milton Gross, MD, Jeffrey Curtis, MD, Edgar Ben-Josef, MD, and Dean Brenner, MD, for their strong support for the protocol conduct.
Supported in part by Young Investigator Award of the American Society of Clinical Oncology, the Radiological Society of North America Seed Grant Program and National Institutes of Health Grant No. NIHP01 CA59827. Presented in part at the 48th Annual Meeting of American Society for Therapeutic Radiology and Oncology, November 6, 2006, Philadelphia, PA. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2006. CA Cancer J Clin 56:106-130, 2006 2. Juweid ME, Cheson BD: Positron-emission tomography and assessment of cancer therapy. N Engl J Med 354:496-507, 2006 3. Lardinois D, Weder W, Hany TF, et al: Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 348:2500-2507, 2003 4. Mac Manus MP, Hicks RJ, Matthews JP, et al: Metabolic (FDG-PET) response after radical radiotherapy/chemoradiotherapy for non-small cell lung cancer correlates with patterns of failure. Lung Cancer 49:95-108, 2005[CrossRef][Medline] 5. Pieterman RM, van Putten JW, Meuzelaar JJ, et al: Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 343:254-261, 2000 6. Eschmann SM, Friedel G, Paulsen F, et al: Repeat (18)F-FDG PET for monitoring neoadjuvant chemotherapy in patients with stage III non-small cell lung cancer. Lung Cancer 55:165-171, 2007[CrossRef][Medline] 7. Mac Manus MP, Hicks RJ, Matthews JP, et al: Positron emission tomography is superior to CT scanning for response assessment after radical radiotherapy/chemoradiotherapy in patients with non–small-cell lung cancer. J Clin Oncol 21:1285-1292, 2003 8. Yamamoto Y, Nishiyama Y, Monden T, et al: Correlation of FDG-PET findings with histopathology in the assessment of response to induction chemoradiotherapy in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 33:140-147, 2006[CrossRef][Medline] 9. 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 21:2651-2657, 2003 10. Choi NC, Fischman AJ, Niemierko A, et al: Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 54:1024-1035, 2002[CrossRef][Medline] 11. Eschmann SM, Friedel G, Paulsen F, et al: (18)F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer. Eur J Nucl Med Mol Imaging 34:463-471, 2007[CrossRef][Medline] 12. Cerfolio RJ, Bryant AS, Winokur TS: Repeat FDG-PET after neoadjuvant therapy is a predictor of pathologic response in patients with non-small cell lung cancer. Ann Thorac Surg 78:1903-1909, 2004; discussion 1909 13. Pöttgen C, Levegrun S, Theegarten D, 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 12:97-106, 2006 14. Hellwig D, Graeter TP, Ukena D, et al: Value of F-18-fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma. J Thorac Cardiovasc Surg 128:892-899, 2004 15. Hicks RJ, Mac Manus MP, Matthews JP, 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 60:412-418, 2004[CrossRef][Medline] 16. Shankar LK, Hoffman JM, Bacharach S, et al: Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 47:1059-1066, 2006 17. 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 92:205-216, 2000 18. Dose Schwarz J, Bader M, Jenicke L, et al: Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET. J Nucl Med 46:1144-1150, 2005 19. 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 19:3058-3065, 2001 20. Kostakoglu L, Coleman M, Leonard JP, et al: PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med 43:1018-1027, 2002 21. Brun E, Ohlsson T, Erlandsson K, et al: Early prediction of treatment outcome in head and neck cancer with 2-18-FDG PET. Acta Oncol 36:741-747, 1997[Medline] 22. Hautzel H, Muller-Gartner HW: Early changes in fluorine-18-FDG uptake during radiotherapy. J Nucl Med 38:1384-1386, 1997 23. Erdi YE, Macapinlac H, Rosenzweig KE, et al: Use of PET to monitor the response of lung cancer to radiation treatment. Eur J Nucl Med 27:861-866, 2000[CrossRef][Medline] 24. van Baardwijk A, Bosmans G, Dekker A, et al: Time trends in the maximal uptake of FDG on PET scan during thoracic radiotherapy: A prospective study in locally advanced non-small cell lung cancer (NSCLC) patients. Radiother Oncol 82:145-152, 2007[CrossRef][Medline] 25. Feng M, Kong FM, Frey KA, et al: The use of FDG-PET to assess tumor response during radiotherapy for non-small cell lung cancer and its potential impact on normal tissue sparing or tumor dose escalation. Presented at Annual Conference on Radiation Society North America, Chicago, IL, December 1, 2005 26. Kong FM, Ten Haken RK, Schipper MJ, et al: High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: Long-term results of a radiation dose escalation study. Int J Radiat Oncol Biol Phys 63:324-333, 2005[CrossRef][Medline] Submitted December 14, 2006; accepted April 19, 2007.
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
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