Radiotherapy plays an important role in the treatment for thoracic cancers. Accurate diagnosis is essential to correctly perform curative radiotherapy. Tumor delineation is also important to prevent geographic misses in radiotherapy planning. Currently, planning is based on computed tomography (CT) imaging when radiation oncologists manually contour the tumor, and this practice often induces interobserver variability. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been reported to enable accurate staging and detect tumor extension in several thoracic cancers, such as lung cancer and esophageal cancer. FDG-PET imaging has many potential advantages in radiotherapy planning for these cancers, because it can add biological information to conventional anatomical images and decrease the inter-observer variability. FDG-PET improves radiotherapy volume and enables dose escalation without causing severe side effects, especially in lung cancer patients. The main advantage of FDG-PET for esophageal cancer patients is the detection of unrecognized lymph node or distal metastases. However, automatic delineation by FDG-PET is still controversial in these tumors, despite the initial expectations. We will review the role of FDG-PET in radiotherapy for thoracic cancers, including lung cancer and esophageal cancer. 1. Introduction Radiotherapy plays an important role in the treatment of thoracic cancers, such as non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and esophageal cancer [1, 2]. Recent advances in accurate diagnosis improve the practice of curative radiotherapy, because patients with unsuspected metastases may avoid unnecessary local therapies and receive necessary systemic treatment. Accurate delineation of tumor volume is also important to prevent geographic misses in treatment planning. Indeed, an underestimation of tumor extension will result in tumor recurrence. In contrast, overestimation of the extension may increase unnecessary side effects. Therefore, delineation of tumor volumes is a crucial factor in curative radiotherapy. Currently, treatment planning is based on computed tomography (CT) imaging to contour the tumor. Tumor delineation is manually performed by each radiation oncologist in clinical practice, which leads to interobserver variability in tumor delineation. Accurate delineation of tumor volume requires the identification of anatomic borders of tumors based on accurate diagnosis. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and PET/CT have been reported to enable accurate staging and
References
[1]
H. Onishi, H. Shirato, Y. Nagata et al., “Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study,” Journal of Thoracic Oncology, vol. 2, no. 7, pp. S94–S100, 2007.
[2]
I. S. Grills, V. S. Mangona, R. Welsh et al., “Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 28, no. 6, pp. 928–935, 2010.
[3]
D. Lardinois, W. Weder, T. F. Hany et al., “Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography,” The New England Journal of Medicine, vol. 348, no. 25, pp. 2500–2507, 2003.
[4]
G. Lammering, D. De Ruysscher, A. Van Baardwijk et al., “The use of FDG-PET to target tumors by radiotherapy,” Strahlentherapie und Onkologie, vol. 186, no. 9, pp. 471–481, 2010.
[5]
R. M. Pieterman, J. W. G. Van Putten, J. J. Meuzelaar et al., “Preoperative staging of non-small-cell lung cancer with positron- emission tomography,” The New England Journal of Medicine, vol. 343, no. 4, pp. 254–261, 2000.
[6]
D. Lardinois, W. Weder, T. F. Hany et al., “Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography,” The New England Journal of Medicine, vol. 348, no. 25, pp. 2500–2507, 2003.
[7]
M. P. Mac Manus, R. J. Hicks, D. L. Ball, et al., “F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma: powerful correlation with survival and high impact on treatment,” Cancer, vol. 92, no. 2, pp. 886–895, 2001.
[8]
M. P. Mac Manus, K. Wong, R. J. Hicks, J. P. Matthews, A. Wirth, and D. L. Ball, “Early mortality after radical radiotherapy for non-small-cell lung cancer: comparison of PET-staged and conventionally staged cohorts treated at a large tertiary referral center,” International Journal of Radiation Oncology Biology Physics, vol. 52, no. 2, pp. 351–361, 2002.
[9]
M. Kolodziejczyk, L. Kepka, M. Dziuk et al., “Impact of [18F]fluorodeoxyglucose PET-CT staging on treatment planning in radiotherapy incorporating elective nodal irradiation for non-small-cell lung cancer: a prospective study,” International Journal of Radiation Oncology Biology Physics, vol. 80, no. 4, pp. 1008–1014, 2011.
[10]
J. Bradley, W. L. Thorstad, S. Mutic et al., “Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer,” International Journal of Radiation Oncology Biology Physics, vol. 59, no. 1, pp. 78–86, 2004.
[11]
C. Greco, K. Rosenzweig, G. L. Cascini, and O. Tamburrini, “Current status of PET/CT for tumour volume definition in radiotherapy treatment planning for non-small cell lung cancer (NSCLC),” Lung Cancer, vol. 57, no. 2, pp. 125–134, 2007.
[12]
A. C. Paulino and P. A. S. Johnstone, “FDG-PET in radiotherapy treatment planning: pandora's box?” International Journal of Radiation Oncology Biology Physics, vol. 59, no. 1, pp. 4–5, 2004.
[13]
Y. E. Erdi, O. Mawlawi, S. M. Larson et al., “Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding,” Cancer, vol. 80, no. 12, supplement, pp. 2505–2509, 1997.
[14]
U. Nestle, S. Kremp, A. Schaefer-Schuler et al., “Comparison of different methods for delineation of18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-small cell lung cancer,” Journal of Nuclear Medicine, vol. 46, no. 8, pp. 1342–1348, 2005.
[15]
M. Wanet, J. A. Lee, B. Weynand et al., “Gradient-based delineation of the primary GTV on FDG-PET in non-small cell lung cancer: a comparison with threshold-based approaches, CT and surgical specimens,” Radiotherapy and Oncology, vol. 98, no. 1, pp. 117–125, 2011.
[16]
M. Warner-Wasik, A. D. Nelson, W. Choi, et al., “What is the bestway to contour lung tumors on PET scans? Multiobserver varidation of a gradient-based method using a NSCLC digital PET phantom,” International Journal of Radiation Oncology, Biology, Physics, vol. 82, no. 3, pp. 1164–1171, 2012.
[17]
K. J. Biehl, F. M. Kong, F. Dehdashti et al., “18F-FDG PET definition of gross tumor volume for radiotherapy of non-small cell lung cancer: is a single standardized uptake value threshold approach appropriate?” Journal of Nuclear Medicine, vol. 47, no. 11, pp. 1808–1812, 2006.
[18]
R. Hong, J. Halama, D. Bova, A. Sethi, and B. Emami, “Correlation of PET standard uptake value and CT window-level thresholds for target delineation in CT-based radiation treatment planning,” International Journal of Radiation Oncology Biology Physics, vol. 67, no. 3, pp. 720–726, 2007.
[19]
A. van Baardwijk, G. Bosmans, L. Boersma et al., “PET-CT-Based Auto-Contouring in Non-Small-Cell Lung Cancer Correlates With Pathology and Reduces Interobserver Variability in the Delineation of the Primary Tumor and Involved Nodal Volumes,” International Journal of Radiation Oncology Biology Physics, vol. 68, no. 3, pp. 771–778, 2007.
[20]
E. P. Visser, M. E. P. Philippens, L. Kienhorst et al., “Comparison of tumor volumes derived from glucose metabolic rate maps and SUV maps in dynamic 18F-FDG PET,” Journal of Nuclear Medicine, vol. 49, no. 6, pp. 892–898, 2008.
[21]
N. Rodríguez, X. Sanz, C. Trampal et al., “18F-FDG PET definition of gross tumor volume for radiotherapy of lung cancer: is the tumor uptake value-based approach appropriate for lymph node delineation?” International Journal of Radiation Oncology Biology Physics, vol. 78, no. 3, pp. 659–666, 2010.
[22]
S. Devic, N. Tomic, S. Faria, S. Menard, R. Lisbona, and S. Lehnert, “Defining radiotherapy target volumes using 18F-fluoro-deoxy- glucose positron emission tomography/computed tomography: still a pandora's box?” International Journal of Radiation Oncology Biology Physics, vol. 78, no. 5, pp. 1555–1562, 2010.
[23]
S. K. Vinod, S. Kumar, L. C. Holloway, and J. Shafiq, “Dosimetric implications of the addition of 18 fluorodeoxyglucose-positron emission tomography in CT-based radiotherapy planning for non-small-cell lung cancer: ORIGINAL ARTICLE,” Journal of Medical Imaging and Radiation Oncology, vol. 54, no. 2, pp. 152–160, 2010.
[24]
J. Fleckenstein, D. Hellwig, S. Kremp et al., “F-18-FDG-PET confined radiotherapy of locally advanced NSCLC with concomitant chemotherapy: results of the PET-PLAN pilot trial,” International Journal of Radiation Oncology, Biology, Physics, vol. 81, no. 4, pp. 283–289, 2011.
[25]
S. Lin, B. Han, L. Yu, D. Shan, R. Wang, and X. Ning, “Comparison of PET-CT images with the histopathological picture of a resectable primary tumor for delineating GTV in nonsmall cell lung cancer,” Nuclear Medicine Communications, vol. 32, no. 6, pp. 479–485, 2011.
[26]
J. Van de Steene, N. Linthout, J. De Mey et al., “Definition of gross tumor volume in lung cancer: inter-observer variability,” Radiotherapy and Oncology, vol. 62, no. 1, pp. 37–39, 2002.
[27]
J. Van de Steene, N. Linthout, J. De Mey et al., “Definition of gross tumor volume in lung cancer: inter-observer variability,” Radiotherapy and Oncology, vol. 62, no. 1, pp. 37–39, 2002.
[28]
C. B. Caldwell, K. Mah, Y. C. Ung et al., “Observer variation in contouring gross tumor volume in patients with poorly defined non-small-cell lung tumors on CT: the impact of 18FDG-hybrid PET fusion,” International Journal of Radiation Oncology Biology Physics, vol. 51, no. 4, pp. 923–931, 2001.
[29]
A. van Baardwijk, G. Bosmans, L. Boersma et al., “PET-CT-based auto-contouring in non-small-cell lung cancer correlates with pathology and reduces interobserver variability in the delineation of the primary tumor and involved nodal volumes,” International Journal of Radiation Oncology Biology Physics, vol. 68, no. 3, pp. 771–778, 2007.
[30]
M. A. Henderson, D. J. Hoopes, J. W. Fletcher et al., “A pilot trial of serial 18F-fluorodeoxyglucose positron emission tomography in patients with medically inoperable stage I non-small-cell lung cancer treated with hypofractionated stereotactic body radiotherapy,” International Journal of Radiation Oncology Biology Physics, vol. 76, no. 3, pp. 789–795, 2010.
[31]
N. Andratschke, F. Zimmermann, E. Boehm et al., “Stereotactic radiotherapy of histologically proven inoperable stage I non-small cell lung cancer: patterns of failure,” Radiotherapy and Oncology, vol. 101, no. 2, pp. 245–249, 2011.
[32]
A. Takeda, N. Yokosuka, T. Ohashi, et al., “The maximum standardized uptake value (SUVmax) on FDG-PET is a strong predictor of local recurrence for localized non-small-cell lung cancer after stereotactic body radiotherapy (SBRT),” Radiotherapy and Oncology, vol. 101, no. 2, pp. 291–297, 2011.
[33]
D. J. Hoopes, M. Tann, J. W. Fletcher et al., “FDG-PET and stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer,” Lung Cancer, vol. 56, no. 2, pp. 229–234, 2007.
[34]
D. Coon, A. S. Gokhale, S. A. Burton, D. E. Heron, C. Ozhasoglu, and N. Christie, “Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography - based treatment planning,” Clinical Lung Cancer, vol. 9, no. 4, pp. 217–221, 2008.
[35]
S. Sura, C. Greco, D. Gelblum, E. D. Yorke, A. Jackson, and K. E. Rosenzweig, “(18)F-fluorodeoxyglucose positron emission tomography-based assessment of local failure patterns in non-small-cell lung cancer treated with definitive radiotherapy,” International Journal of Radiation Oncology Biology Physics, vol. 70, no. 5, pp. 1397–1402, 2008.
[36]
A. Abramyuk, S. Tokalov, K. Z？phel et al., “Is pre-therapeutical FDG-PET/CT capable to detect high risk tumor subvolumes responsible for local failure in non-small cell lung cancer?” Radiotherapy and Oncology, vol. 91, no. 3, pp. 399–404, 2009.
[37]
S. E. Schild, “Elective Nodal Irradiation (ENI) doesn't appear to provide a clear benefit for patients with unresectable non-small-cell lung cancer (NSCLC),” International Journal of Radiation Oncology Biology Physics, vol. 72, no. 2, pp. 311–312, 2008.
[38]
C. R. Kelsey, L. B. Marks, and E. Glatstein, “Elective nodal irradiation for locally advanced non-small-cell lung cancer: it's called cancer for a reason,” International Journal of Radiation Oncology Biology Physics, vol. 73, no. 5, pp. 1291–1292, 2009.
[39]
K. E. Rosenzweig, S. Sura, A. Jackson, and E. Yorke, “Involved-field radiation therapy for inoperable non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 25, no. 35, pp. 5557–5561, 2007.
[40]
J. D. Bradley, K. Bae, M. V. Graham et al., “Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117,” Journal of Clinical Oncology, vol. 28, no. 14, pp. 2475–2480, 2010.
[41]
G. M. M. Videtic, T. W. Rice, S. Murthy et al., “Utility of positron emission tomography compared with mediastinoscopy for delineating involved lymph nodes in stage III lung cancer: insights for radiotherapy planning from a surgical cohort,” International Journal of Radiation Oncology Biology Physics, vol. 72, no. 3, pp. 702–706, 2008.
[42]
L. J. Vanuytsel, J. F. Vansteenkiste, S. G. Stroobants et al., “The impact of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) lymph node staging on the radiation treatment volumes in patients with non-small cell lung cancer,” Radiotherapy and Oncology, vol. 55, no. 3, pp. 317–324, 2000.
[43]
D. De Ruysscher, S. Wanders, E. Van Haren et al., “Selective mediastinal node irradiation based on FDG-PET scan data in patients with non-small-cell lung cancer: a prospective clinical study,” International Journal of Radiation Oncology Biology Physics, vol. 62, no. 4, pp. 988–994, 2005.
[44]
D. M. Jackman and B. E. Johnson, “Small-cell lung cancer,” The Lancet, vol. 366, no. 9494, pp. 1385–1396, 2005.
[45]
B. M. Fischer, J. Mortensen, S. W. Langer et al., “A prospective study of PET/CT in initial staging of small-cell lung cancer: comparison with CT, bone scintigraphy and bone marrow analysis,” Annals of Oncology, vol. 18, no. 2, pp. 338–345, 2007.
[46]
J. D. Bradley, F. Dehdashti, M. A. Mintum, R. Govindan, K. Trinkaus, and B. A. Siegel, “Positron emission tomography in limited-stage small-cell lung cancer: a prospective study,” Journal of Clinical Oncology, vol. 22, no. 16, pp. 3248–3254, 2004.
[47]
S. Niho, H. Fujii, K. Murakami et al., “Detection of unsuspected distant metastases and/or regional nodes by FDG-PET in LD-SCLC scan in apparent limited-disease small-cell lung cancer,” Lung Cancer, vol. 57, no. 3, pp. 328–333, 2007.
[48]
N. Arslan, M. Tuncel, O. Kuzhan, et al., “Evaluation of outcome prediction and disease extension by quantitative 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography in patients with small cell lung cancer,” Annals of Nuclear Medicine, vol. 25, no. 6, pp. 406–413, 2011.
[49]
P. Baas, J. S. A. Belderbos, S. Senan et al., “Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study,” British Journal of Cancer, vol. 94, no. 5, pp. 625–630, 2006.
[50]
D. De Ruysscher, R. H. Bremer, F. Koppe et al., “Omission of elective node irradiation on basis of CT-scans in patients with limited disease small cell lung cancer: a phase II trial,” Radiotherapy and Oncology, vol. 80, no. 3, pp. 307–312, 2006.
[51]
G. M. M. Videtic, J. S. A. Belderbos, F. M. (Spring) Kong F.-M., L. Kepka, M. K. Martel, and B. Jeremic, “Report from the International Atomic Energy Agency (IAEA) consultants' meeting on elective nodal irradiation in lung cancer: small-cell lung cancer (SCLC),” International Journal of Radiation Oncology Biology Physics, vol. 72, no. 2, pp. 327–334, 2008.
[52]
J. van Loon, D. De Ruysscher, R. Wanders et al., “Selective nodal irradiation on basis of (18)FDG-PET scans in limited-disease small-cell lung cancer: a prospective study,” International Journal of Radiation Oncology Biology Physics, vol. 77, no. 2, pp. 329–336, 2010.
[53]
S. M. Shirvani, R. Komaki, J. V. Heymach, F. V. Fossella, and J. Y. Chang, “Positron emission tomography/computed tomography-guided intensity-modulated radiotherapy for limited-stage small-cell lung cancer,” International Journal of Radiation Oncology, Biology, Physics, vol. 82, no. 1, pp. e91–e97, 2012.
[54]
J. Van Loon, C. Offermann, M. ？llers et al., “Early CT and FDG-metabolic tumour volume changes show a significant correlation with survival in stage I-III small cell lung cancer: a hypothesis generating study,” Radiotherapy and Oncology, vol. 99, no. 2, pp. 172–175, 2011.
[55]
C. T. Muijs, J. C. Beukema, J. Pruim et al., “A systematic review on the role of FDG-PET/CT in tumour delineation and radiotherapy planning in patients with esophageal cancer,” Radiotherapy and Oncology, vol. 97, no. 2, pp. 165–171, 2010.
[56]
P. Flamen, A. Lerut, E. Van Cutsem et al., “Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma,” Journal of Clinical Oncology, vol. 18, no. 18, pp. 3202–3210, 2000.
[57]
E. P. M. Van Vliet, M. H. Heijenbrok-Kal, M. G. M. Hunink, E. J. Kuipers, and P. D. Siersema, “Staging investigations for oesophageal cancer: a meta-analysis,” British Journal of Cancer, vol. 98, no. 3, pp. 547–557, 2008.
[58]
V. Gondi, K. Bradley, M. Mehta et al., “Impact of hybrid fluorodeoxyglucose positron-emission tomography/computed tomography on radiotherapy planning in esophageal and non-small-cell lung cancer,” International Journal of Radiation Oncology Biology Physics, vol. 67, no. 1, pp. 187–195, 2007.
[59]
L. Moureau-Zabotto, E. Touboul, D. Lerouge et al., “Impact of CT and 18F-deoxyglucose positron emission tomography image fusion for conformal radiotherapy in esophageal carcinoma,” International Journal of Radiation Oncology Biology Physics, vol. 63, no. 2, pp. 340–345, 2005.
[60]
D. Vesprini, Y. Ung, R. Dinniwell et al., “Improving observer variability in target delineation for gastro-oesophageal cancer–the role of (18F)fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography,” Clinical Oncology, vol. 20, no. 8, pp. 631–638, 2008.
[61]
C. T. Muijs, L. M. Schreurs, D. M. Busz et al., “Consequences of additional use of PET information for target volume delineation and radiotherapy dose distribution for esophageal cancer,” Radiotherapy and Oncology, vol. 93, no. 3, pp. 447–453, 2009.
[62]
A. Konski, M. Doss, B. Milestone et al., “The integration of 18-fluoro-deoxy-glucose positron emission tomography and endoscopic ultrasound in the treatment-planning process for esophageal carcinoma,” International Journal of Radiation Oncology Biology Physics, vol. 61, no. 4, pp. 1123–1128, 2005.
[63]
X. Zhong, J. Yu, B. Zhang et al., “Using 18F-fluorodeoxyglucose positron emission tomography to estimate the length of gross tumor in patients with squamous cell carcinoma of the esophagus,” International Journal of Radiation Oncology Biology Physics, vol. 73, no. 1, pp. 136–141, 2009.
[64]
T. S. Hong, J. H. Killoran, M. Mamede, and H. J. Mamon, “Impact of Manual and Automated Interpretation of Fused PET/CT Data on Esophageal Target Definitions in Radiation Planning,” International Journal of Radiation Oncology Biology Physics, vol. 72, no. 5, pp. 1612–1618, 2008.
[65]
F. S. Vali, S. Nagda, W. Hall et al., “Comparison of standardized uptake value-based positron emission tomography and computed tomography target volumes in esophageal cancer patients undergoing radiotherapy,” International Journal of Radiation Oncology Biology Physics, vol. 78, no. 4, pp. 1057–1063, 2010.
[66]
L. M. A. Schreurs, D. M. Busz, G. M. R. M. Paardekooper et al., “Impact of 18-fluorodeoxyglucose positron emission tomography on computed tomography defined target volumes in radiation treatment planning of esophageal cancer: reduction in geographic misses with equal inter-observer variability,” Diseases of the Esophagus, vol. 23, no. 6, pp. 493–501, 2010.
[67]
D. De Ruysscher, U. Nestle, R. Jeraj, M. Macmanus, et al., “PET scans in radiotherapy planning of lung cancer,” Lung Cancer, vol. 75, no. 2, pp. 141–145, 2012.
[68]
S. A. Nehmeh and Y. E. Erdi, “Respiratory motion in positron emission tomography/computed tomography: a review,” Seminars in Nuclear Medicine, vol. 38, no. 3, pp. 167–176, 2008.
[69]
Y. Sakaguchi, T. Mitsumoto, T. Zhang et al., “Importance of gated CT acquisition for the quantitative improvement of the gated PET/CT in moving phantom,” Annals of Nuclear Medicine, vol. 24, no. 7, pp. 507–514, 2010.
[70]
J. Daouk, M. Leloire, L. Fin, et al., “Respiratory-gated 18F-FDG PET imaging in lung cancer: effects on sensitivity and specificity,” Acta Radiologica, vol. 52, no. 6, pp. 651–657, 2011.
[71]
J. S. Brockenbrough, T. Souquet, J. K. Morihara, et al., “Tumor 3′-deoxy-3′-(18)F-fluorothymidine ((18)F-FLT) uptake by PET correlates with thymidine kinase 1 expression: static and kinetic analysis of (18)F-FLT PET studies in lung tumors,” Journal of Nuclear Medicine, vol. 52, no. 8, pp. 1181–1188, 2011.
[72]
W. Yang, Y. Zhang, Z. Fu et al., “Imaging of proliferation with 18F-FLT PET/CT versus 18F-FDG PET/CT in non-small-cell lung cancer,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 37, no. 7, pp. 1291–1299, 2010.
