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[18F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer

[18F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer Abstract Objective: Positron emission tomography (PET) is being increasingly used as an accurate and non-invasive modality in diagnosis, staging and post-therapy assessment in patients with lung cancer. In this study, we examine whether the uptake of [18F]fluorodeoxyglucose (FDG), a marker of increased glucose metabolism in neoplastic cells, is of prognostic value in patients with primary lung cancer. Methods: We have retrospectively analyzed 77 patients (mean age, 63.0 years; male/female ratio, 53:24) with primary lung cancers who underwent whole body and localized thoracic PET as part of their diagnostic and staging procedures prior to consideration of surgical resection. The standardized uptake value (SUV) of injected FDG for each primary lesion was correlated with tumour histology and the patient's clinical outcome. Results: A SUV of 20 or greater was found to be of significant prognostic value. The chance of survival (with 95% confidence intervals (CI)) at 12 months post-surgery for the various SUV groups was as follows: 75.2% (59.6–85.5) for SUV≪10; 67.5% (29.0–88.2) for SUV 10–≪12; 63.6% (29.7–84.5) for SUV 12–≪15; 66.7% (19.5–90.4) for SUV 15–≪20; 16.7% (0.01–0.52) for SUV≫20. A SUV of 20 or more is associated with a 4.66 times increase in hazard, compared with lower levels of SUV. We found no significant correlation between tumour histology and SUV. Conclusion: We have previously reported on the significant advantages of PET in the staging and surgical care of patients with lung cancer. The present study adds further support for an additional prognostic role for PET in the management of thoracic malignancy as determined by the amount of labelled-FDG taken up by the primary lesion. Lung neoplasm, Positron emission tomography, Surgery, Prognosis 1 Introduction Positron emission tomography (PET) is now a widely accepted imaging modality, which is finding an expanding role in clinical practice. Recent technical advances and particularly the use of the radio-labelled tracer, [18F]fluorodeoxyglucose (FDG), has made this imaging modality increasingly popular in the diagnosis and management of lung cancer [1,2]. With the availability of whole body imaging, its use now ranges from that of a diagnostic tool to its role in the disease staging and post-therapy assessment in patients with lung neoplasm. This is reflected in the recent exponential rise in the number of publications on the use of PET scanning in lung cancer. PET can make use of the increased glucose metabolism of malignant cells by using radio-isotope-labelled FDG, which, once taken up, remains trapped inside the cells following its initial phosphorylation [3]. The amount of FDG taken up by the abnormal lesion can be represented by semiquantitative measures, such as the standardized uptake value (SUV) or ratio (SUR), and made comparable between patients [4]. Previous studies have correlated FDG uptake with lung tumour growth rate [5]. We have previously reported on the greater sensitivity, specificity and accuracy of PET over computed tomography (CT) in the staging of primary lung cancer [2]. A strong correlation between FDG uptake and subsequent survival in lung cancer patients has been reported [6]. In this study, we have retrospectively analyzed our PET scanning data to further assess any such prognostic relation between the SUV of the primary lung lesion and patient survival. 2 Materials and methods The patient demographics and imaging methodology used in this study have been detailed previously [2]. In brief, between November 1992 and July 1995, all patients referred to a single surgeon for possible surgical resection of their lung lesion underwent whole body and localized thoracic PET. Tissue diagnosis, SUV and survival data were available for 77 of the 97 patients who were previously reported on with respect to their prognostic significance on clinical staging by PET [2]. There were 53 male and 24 female patients, with a mean age of 63.0 years (range, 36–77 years). All patients with a biopsy proven lung cancer or with a strong suspicion of malignancy on clinical and CT criteria, and deemed operable clinically and with CT staging (TNM stage 3a or less) were referred for PET imaging. All PET imaging was performed at the Clinical PET Centre at St Thomas’ Hospital, London, UK, on an ECAT 951/31R system (Siemens CTI/Knoxville, TN). Patients were fasted for 6 h and had their baseline serum glucose measured prior to scanning. Each patient received 350 MBq of FDG intravenously and the thoracic emission data was acquired at a mean time of 81 min post injection. The 18-fluorine isotope was produced in a Siemens RDS 112 cyclotron at the same centre. Attenuation correction of the thoracic images was made following transmission scans using a germanium-68 source. The spatial resolution of the attenuation corrected thoracic images was 13 mm. Once reconstructed, the scan views (transaxial, coronal and sagittal) were viewed on a SUN workstation and reported by two nuclear physicians who were blinded to the patient history. A third reporter resolved any dissimilar reports. Using the standard equation [7], the SUV was calculated for each abnormal primary lesion above 10 mm in size from the attenuation corrected thoracic images. This analysis did not include the mediastinal lymph nodes. Disease staging was carried out as per the consensus tumour/node/metastasis (TNM) definitions [8] on the basis of clinical, laboratory and bronchoscopic evaluation, as well as on CT criteria and PET analysis. Histological diagnosis was obtained from a combination of bronchoscopy, fine needle transthoracic biopsy, or at thoracotomy. Deaths were recorded from the Thames Cancer Registry, which keeps records of all cancer-related deaths. 2.1 Data analysis All statistical analysis was performed on the Stata Statistical Software (Stata Corporation, TX). Cox regression for standard variables was used for the univariate analysis of age, sex, SUV, disease stage and histology. Hazard ratios (HR) with 95% confidence intervals (CI) were also calculated. A P value of ≪0.05 was considered significant. Kaplan–Meier survival values were obtained for different SUV levels. 3 Results The following histological types of primary lung tumours were diagnosed in the 77 patients: squamous cell carcinoma, 45; adenocarcinoma, 18; large cell carcinoma, ten; small cell cancer, two; and carcinoid, two. The mean SUV of all the malignant lesions was 11.7±11.3 (mean±SD), and no significant correlation was found between the SUV and tumour histology as previously reported [2]. Fig. 1 shows Kaplan–Meier estimates at SUV levels of 15 and 20. The median survival in months (HR and 95% CI) of patients at various SUV levels or above were as follows: 33 patients with SUV≥10 (HR, 1.3; with CI, 0.7–2.6) had a median survival of 25 months; 23 patients with SUV≥12 (HR, 1.7; with CI, 0.8–3.2) had a median survival of 22 months; 12 patients with SUV≥15 (HR, 2.3; with 95% CI, 1.0–5.0) had a median survival of 9 months; and the six patients with SUV≥20 (HR, 4.7; with 95% CI, 1.9–11.4) had a median survival of only 6 months. Fig. 1 shows the Kaplan–Meier estimates at SUV levels at or above 15 and 20. Fig. 1 Open in new tabDownload slide The Kaplan–Meier estimates at SUVs of 15 and 20. Fig. 1 Open in new tabDownload slide The Kaplan–Meier estimates at SUVs of 15 and 20. Table 1 and Fig. 2 show the correlation between SUV and the chance of survival at a fixed point after surgery. The correlation reaches a level of significance at or above a SUV of 20. Table 1 Open in new tabDownload slide The correlation between SUV and the chance of survival at 12 months post-operatively Table 1 Open in new tabDownload slide The correlation between SUV and the chance of survival at 12 months post-operatively Fig. 2 Open in new tabDownload slide Graphically, the Kaplan–Meier survival estimates by SUV groups. Analysis time refers to months. Fig. 2 Open in new tabDownload slide Graphically, the Kaplan–Meier survival estimates by SUV groups. Analysis time refers to months. 4 Discussion Of the standard protocols in the diagnosis and staging of lung cancer, both CT and mediastinal biopsy have their limitations and disadvantages. While providing detailed anatomical information, CT is not specific for malignancy and has a poor sensitivity in the staging of primary lung cancer [8]. Mediastinal biopsy has a higher sensitivity for assessing mediastinal involvement [9], but has the disadvantage of necessitating an invasive procedure. Additionally, these investigations do not give adequate information to forecast the future clinical outcome for the patient. At best, this has to wait for the definitive peri-, or more commonly, post-operative staging. Despite the initial reservations, just a few years ago by the American Thoracic Society and the European Respiratory Society, about the role of PET in lung cancer, numerous studies, including our own [2], have reported on the greater sensitivity and specificity of PET over CT in the mediastinal staging of bronchogenic carcinoma [2,10–13]. In our previous study, we also reported on its positive role in diagnosing unsuspected distant metastases, as well as in altering the management in 37% of the patients referred for surgical resection [2]. Our results from the present study confirm the recently reported association between SUV of the primary lung lesion with patient outcome [6]. Ahuja et al. [6] reported a significant correlation between a SUV of ≫10 and poor outcome with a median survival of 11.4 months. This was reduced to 5.7 months if the tumour size exceeded 3 cm in size. When analyzing median survival estimates, we have found a similar prognostic value of PET scanning for patients with lung cancer at SUVs of 15 and above. Our results show a dismal prognosis above a SUV of 20, at which the median survival is only 6 months. However, median survival times are not statistically helpful in a study of this size and follow-up. This is because in some of the SUV groups, less than half of the patients die during the study period, and therefore, there is no median survival time. In addition, the significance level at SUV≥15 is misleading in that some patients in this group are also in the SUV≫20 group. Additionally, choosing an optimal cut-off SUV with the best discriminative value would amount to choosing one with the largest effect after looking at the data. This clearly would have been a biased analysis. We have therefore analyzed the data with reference to SUV range groups and correlated this with the chance of survival to a fixed point (12 months) post-operatively. In this way, the significance of SUV with respect to survival only occurs at or above an SUV of 20, this being the nearest whole number discriminative value. Interpretation of the FDG-PET images has its limitations [14]. False negative results are possible with low-grade malignancy, microscopic malignant lesions below the size of resolution, hyperglycaemia and highly metabolic adjacent sites. False positives can occur with active infection, acute inflammation, recent surgical wounds and muscle hypermetabolism. Despite this, with good clinical judgement and with the additional anatomical information provided by the CT scan, PET appears to have a definitive place in the management of lung cancer. In addition to its non-invasive nature, a greater accuracy in staging and possible cost effectiveness [15], it has certainly in our practice not only reduced the number of mediastinal biopsy procedures, but now offers a further advantage with its prognostic value. ✩ Presented at the 13th Annual Meeting of the European Association for Cardio-thoracic Surgery, Glasgow, Scotland, UK, September 5–8, 1999. Appendix A Conference discussion Dr D. Van Raemdonck (Leuven, Belgium): Thank you for this excellent paper. Can you tell us a bit how PET scanning in your institution has changed your attitude towards invasive mediastinal staging? Have you changed your indication for mediastinoscopy or is it still the same as before? Mr Dhital: It has certainly reduced the number of mediastinal biopsies that are being performed. Dr W. Weder (Zurich, Switzerland): You correlated the prognosis with the FDG uptake, but you didn't show us the TNM stage. How was this correlated? Mr Dhital: We have previously reported [2] on the lack of correlation between SUV and tumour stage. While you find a correlation between SUV and tumour size, there does not appear to be a correlation between SUV and staging or histological diagnosis. Dr J. Hasse (Freiburg, Germany): One of the limitations of PET, so far as I know, is the size of tumour or metastasis. What is the critical size when a metastasis or malignant cells can be detected with modern PET facilities? Mr Dhital: In this particular study, the PET resolution was used at 13 mm on CT-positive lesions of 10 mm or more. Dr Hasse: Well, it could be that a small tumour with a high metabolism will be indicated by the PET even if it is only 5 mm of size. Are you informed about the critical size by your PET specialists? Mr Dhital: We use a 13 mm resolution. But, having said that, if the SUV is below 2.5, we accept that to be a benign lesion. Mr K. Jeyasingham (Bristol, UK): You did say that there was no correlation to TNM. But did you in your series have any correlation between the SUV and the cellular differentiation of the tumour itself? That may have a role. Mr Dhital: We haven't looked into that. Mr J. Cockburn (Aberdeen, UK): Can I just ask the audience how many people have access to PET scanning in their practice? (Show of hands) It's quite a high percentage. Cost is one of the problems still, isn't it? Have you any comments on that just before we leave this subject? Mr Dhital: Currently, the cost in our centre is over £700/scan. But that I think can be reduced substantially with gamma counter machines to about a couple of hundred pounds. Hopefully, the prices will keep coming down. References [1] Lowe V.J. , Naunheim K.S. . Current role of positron emission tomography in thoracic oncology , Thorax , 1998 , vol. 53 (pg. 703 - 712 ) Google Scholar Crossref Search ADS PubMed WorldCat [2] Saunders C.A.B. , Dussek J. , O'Doherty M.J. , Maisey M.N. . An evaluation of 18F-FDG whole body PET imaging in the staging of lung cancer , Ann Thorac Surg , 1999 , vol. 67 (pg. 790 - 797 ) Google Scholar Crossref Search ADS PubMed WorldCat [3] Gallagher B.M. , Fowler J.S. , Gutterson N.I. , MacGregor R.R. , Wan C.N. , Wolf A.P. . Metabolic trapping as a principle of radiopharmaceutical design: some factors responsible for the biodistribution of [18F]-2-deoxy-2-fluoro-D-glucose , J Nucl Med , 1978 , vol. 19 (pg. 1154 - 1161 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [4] Minn H. , Zasadny K.R. , Quint C.E. , Wahl R.L. . Lung cancer: reproducibility of quantitative measurements for evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET , Radiology , 1995 , vol. 196 (pg. 167 - 173 ) Google Scholar Crossref Search ADS PubMed WorldCat [5] Duhaylongsod F.G. , Lowe V.J. , Patz E.F. , Vaughan A.L. , Coleman R.E. , Wolfe W.G. . Lung tumour growth correlates with glucose metabolism measured by fluoride-18-fluorodeoxyglucose positron emission tomography , Ann Thorac Surg , 1995 , vol. 60 (pg. 1348 - 1352 ) Google Scholar Crossref Search ADS PubMed WorldCat [6] Ahuja V. , Coleman R.E. , Herndon J. , Patz E.F. . The prognostic significance of fluorodeoxyglucose positron emission tomography imaging for patients with non-small cell lung carcinoma , Cancer , 1998 , vol. 83 (pg. 918 - 924 ) Google Scholar Crossref Search ADS PubMed WorldCat [7] Zasadny K.R. , Wahl R.L. . Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction , Radiology , 1993 , vol. 189 (pg. 847 - 850 ) Google Scholar Crossref Search ADS PubMed WorldCat [8] McLoud T.C. , Bourgouin P.M. , Greenberg R.W. , Kosiuk J.P. . Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph nodemapping and sampling , Radiology , 1992 , vol. 182 (pg. 319 - 323 ) Google Scholar Crossref Search ADS PubMed WorldCat [9] Wahl R.L. , Quint L.E. , Greenough R.L. , Meyer C.R. , White R.I. , Orringer M.B. . Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation , Radiology , 1994 , vol. 191 (pg. 371 - 377 ) Google Scholar Crossref Search ADS PubMed WorldCat [10] Dewan N.A. , Reeb S.D. , Gupta N.C. , Gobar L.S. , Scott J.J. . PET-FDG imaging and transthoracic needle lung aspiration biopsy in evaluation of pulmonary lesions. A comparative risk-benefit analysis , Chest , 1995 , vol. 108 (pg. 441 - 446 ) Google Scholar Crossref Search ADS PubMed WorldCat [11] Scott W.J. , Gobar L.S. , Terry J.D. , Dewan N.A. , Sunderland J.J. . Mediastinal lymph node staging of non-small cell lung cancer: a prospective comparison of computed tomography and positron emission tomography , J Thorac Cardiovasc Surg , 1996 , vol. 111 (pg. 642 - 646 ) Google Scholar Crossref Search ADS PubMed WorldCat [12] Steinert H.C. , Hauser M. , Alleman F. , Engel F. , Berthold T. , von Shulthess G.K. , Weder W. . Non-small cell lung cancer: nodal staging with FDG-PET versus CT with correlative lymph node mapping and sampling , Radiology , 1997 , vol. 202 (pg. 441 - 446 ) Google Scholar Crossref Search ADS PubMed WorldCat [13] Gupta N.C. , Graeber G.M. , Rogers J.S. , Bishop H.A. . Comparative efficacy of positron emission tomography with FDG and computed tomographic scanning in preoperative staging of non-small cell lung cancer , Ann Surg , 1999 , vol. 229 (pg. 286 - 291 ) Google Scholar Crossref Search ADS PubMed WorldCat [14] Lowe V.J. , Naunheim K.S. . Positron emission tomography in lung cancer , Ann Thorac Surg , 1998 , vol. 65 (pg. 1821 - 1829 ) Google Scholar Crossref Search ADS PubMed WorldCat [15] Scott W.J. , Shepherd J. , Gambhir S.S. . Cost-effectiveness of FDG for staging non-small cell lung cancer: a decision analysis , Ann Thorac Surg , 1998 , vol. 66 (pg. 1876 - 1883 ) Google Scholar Crossref Search ADS PubMed WorldCat © 2000 Elsevier Science B.V. All rights reserved. Elsevier Science B.V. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

[18F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer

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Oxford University Press
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© 2000 Elsevier Science B.V. All rights reserved.
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Articles
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1010-7940
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1873-734X
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10.1016/S1010-7940(00)00535-2
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Abstract

Abstract Objective: Positron emission tomography (PET) is being increasingly used as an accurate and non-invasive modality in diagnosis, staging and post-therapy assessment in patients with lung cancer. In this study, we examine whether the uptake of [18F]fluorodeoxyglucose (FDG), a marker of increased glucose metabolism in neoplastic cells, is of prognostic value in patients with primary lung cancer. Methods: We have retrospectively analyzed 77 patients (mean age, 63.0 years; male/female ratio, 53:24) with primary lung cancers who underwent whole body and localized thoracic PET as part of their diagnostic and staging procedures prior to consideration of surgical resection. The standardized uptake value (SUV) of injected FDG for each primary lesion was correlated with tumour histology and the patient's clinical outcome. Results: A SUV of 20 or greater was found to be of significant prognostic value. The chance of survival (with 95% confidence intervals (CI)) at 12 months post-surgery for the various SUV groups was as follows: 75.2% (59.6–85.5) for SUV≪10; 67.5% (29.0–88.2) for SUV 10–≪12; 63.6% (29.7–84.5) for SUV 12–≪15; 66.7% (19.5–90.4) for SUV 15–≪20; 16.7% (0.01–0.52) for SUV≫20. A SUV of 20 or more is associated with a 4.66 times increase in hazard, compared with lower levels of SUV. We found no significant correlation between tumour histology and SUV. Conclusion: We have previously reported on the significant advantages of PET in the staging and surgical care of patients with lung cancer. The present study adds further support for an additional prognostic role for PET in the management of thoracic malignancy as determined by the amount of labelled-FDG taken up by the primary lesion. Lung neoplasm, Positron emission tomography, Surgery, Prognosis 1 Introduction Positron emission tomography (PET) is now a widely accepted imaging modality, which is finding an expanding role in clinical practice. Recent technical advances and particularly the use of the radio-labelled tracer, [18F]fluorodeoxyglucose (FDG), has made this imaging modality increasingly popular in the diagnosis and management of lung cancer [1,2]. With the availability of whole body imaging, its use now ranges from that of a diagnostic tool to its role in the disease staging and post-therapy assessment in patients with lung neoplasm. This is reflected in the recent exponential rise in the number of publications on the use of PET scanning in lung cancer. PET can make use of the increased glucose metabolism of malignant cells by using radio-isotope-labelled FDG, which, once taken up, remains trapped inside the cells following its initial phosphorylation [3]. The amount of FDG taken up by the abnormal lesion can be represented by semiquantitative measures, such as the standardized uptake value (SUV) or ratio (SUR), and made comparable between patients [4]. Previous studies have correlated FDG uptake with lung tumour growth rate [5]. We have previously reported on the greater sensitivity, specificity and accuracy of PET over computed tomography (CT) in the staging of primary lung cancer [2]. A strong correlation between FDG uptake and subsequent survival in lung cancer patients has been reported [6]. In this study, we have retrospectively analyzed our PET scanning data to further assess any such prognostic relation between the SUV of the primary lung lesion and patient survival. 2 Materials and methods The patient demographics and imaging methodology used in this study have been detailed previously [2]. In brief, between November 1992 and July 1995, all patients referred to a single surgeon for possible surgical resection of their lung lesion underwent whole body and localized thoracic PET. Tissue diagnosis, SUV and survival data were available for 77 of the 97 patients who were previously reported on with respect to their prognostic significance on clinical staging by PET [2]. There were 53 male and 24 female patients, with a mean age of 63.0 years (range, 36–77 years). All patients with a biopsy proven lung cancer or with a strong suspicion of malignancy on clinical and CT criteria, and deemed operable clinically and with CT staging (TNM stage 3a or less) were referred for PET imaging. All PET imaging was performed at the Clinical PET Centre at St Thomas’ Hospital, London, UK, on an ECAT 951/31R system (Siemens CTI/Knoxville, TN). Patients were fasted for 6 h and had their baseline serum glucose measured prior to scanning. Each patient received 350 MBq of FDG intravenously and the thoracic emission data was acquired at a mean time of 81 min post injection. The 18-fluorine isotope was produced in a Siemens RDS 112 cyclotron at the same centre. Attenuation correction of the thoracic images was made following transmission scans using a germanium-68 source. The spatial resolution of the attenuation corrected thoracic images was 13 mm. Once reconstructed, the scan views (transaxial, coronal and sagittal) were viewed on a SUN workstation and reported by two nuclear physicians who were blinded to the patient history. A third reporter resolved any dissimilar reports. Using the standard equation [7], the SUV was calculated for each abnormal primary lesion above 10 mm in size from the attenuation corrected thoracic images. This analysis did not include the mediastinal lymph nodes. Disease staging was carried out as per the consensus tumour/node/metastasis (TNM) definitions [8] on the basis of clinical, laboratory and bronchoscopic evaluation, as well as on CT criteria and PET analysis. Histological diagnosis was obtained from a combination of bronchoscopy, fine needle transthoracic biopsy, or at thoracotomy. Deaths were recorded from the Thames Cancer Registry, which keeps records of all cancer-related deaths. 2.1 Data analysis All statistical analysis was performed on the Stata Statistical Software (Stata Corporation, TX). Cox regression for standard variables was used for the univariate analysis of age, sex, SUV, disease stage and histology. Hazard ratios (HR) with 95% confidence intervals (CI) were also calculated. A P value of ≪0.05 was considered significant. Kaplan–Meier survival values were obtained for different SUV levels. 3 Results The following histological types of primary lung tumours were diagnosed in the 77 patients: squamous cell carcinoma, 45; adenocarcinoma, 18; large cell carcinoma, ten; small cell cancer, two; and carcinoid, two. The mean SUV of all the malignant lesions was 11.7±11.3 (mean±SD), and no significant correlation was found between the SUV and tumour histology as previously reported [2]. Fig. 1 shows Kaplan–Meier estimates at SUV levels of 15 and 20. The median survival in months (HR and 95% CI) of patients at various SUV levels or above were as follows: 33 patients with SUV≥10 (HR, 1.3; with CI, 0.7–2.6) had a median survival of 25 months; 23 patients with SUV≥12 (HR, 1.7; with CI, 0.8–3.2) had a median survival of 22 months; 12 patients with SUV≥15 (HR, 2.3; with 95% CI, 1.0–5.0) had a median survival of 9 months; and the six patients with SUV≥20 (HR, 4.7; with 95% CI, 1.9–11.4) had a median survival of only 6 months. Fig. 1 shows the Kaplan–Meier estimates at SUV levels at or above 15 and 20. Fig. 1 Open in new tabDownload slide The Kaplan–Meier estimates at SUVs of 15 and 20. Fig. 1 Open in new tabDownload slide The Kaplan–Meier estimates at SUVs of 15 and 20. Table 1 and Fig. 2 show the correlation between SUV and the chance of survival at a fixed point after surgery. The correlation reaches a level of significance at or above a SUV of 20. Table 1 Open in new tabDownload slide The correlation between SUV and the chance of survival at 12 months post-operatively Table 1 Open in new tabDownload slide The correlation between SUV and the chance of survival at 12 months post-operatively Fig. 2 Open in new tabDownload slide Graphically, the Kaplan–Meier survival estimates by SUV groups. Analysis time refers to months. Fig. 2 Open in new tabDownload slide Graphically, the Kaplan–Meier survival estimates by SUV groups. Analysis time refers to months. 4 Discussion Of the standard protocols in the diagnosis and staging of lung cancer, both CT and mediastinal biopsy have their limitations and disadvantages. While providing detailed anatomical information, CT is not specific for malignancy and has a poor sensitivity in the staging of primary lung cancer [8]. Mediastinal biopsy has a higher sensitivity for assessing mediastinal involvement [9], but has the disadvantage of necessitating an invasive procedure. Additionally, these investigations do not give adequate information to forecast the future clinical outcome for the patient. At best, this has to wait for the definitive peri-, or more commonly, post-operative staging. Despite the initial reservations, just a few years ago by the American Thoracic Society and the European Respiratory Society, about the role of PET in lung cancer, numerous studies, including our own [2], have reported on the greater sensitivity and specificity of PET over CT in the mediastinal staging of bronchogenic carcinoma [2,10–13]. In our previous study, we also reported on its positive role in diagnosing unsuspected distant metastases, as well as in altering the management in 37% of the patients referred for surgical resection [2]. Our results from the present study confirm the recently reported association between SUV of the primary lung lesion with patient outcome [6]. Ahuja et al. [6] reported a significant correlation between a SUV of ≫10 and poor outcome with a median survival of 11.4 months. This was reduced to 5.7 months if the tumour size exceeded 3 cm in size. When analyzing median survival estimates, we have found a similar prognostic value of PET scanning for patients with lung cancer at SUVs of 15 and above. Our results show a dismal prognosis above a SUV of 20, at which the median survival is only 6 months. However, median survival times are not statistically helpful in a study of this size and follow-up. This is because in some of the SUV groups, less than half of the patients die during the study period, and therefore, there is no median survival time. In addition, the significance level at SUV≥15 is misleading in that some patients in this group are also in the SUV≫20 group. Additionally, choosing an optimal cut-off SUV with the best discriminative value would amount to choosing one with the largest effect after looking at the data. This clearly would have been a biased analysis. We have therefore analyzed the data with reference to SUV range groups and correlated this with the chance of survival to a fixed point (12 months) post-operatively. In this way, the significance of SUV with respect to survival only occurs at or above an SUV of 20, this being the nearest whole number discriminative value. Interpretation of the FDG-PET images has its limitations [14]. False negative results are possible with low-grade malignancy, microscopic malignant lesions below the size of resolution, hyperglycaemia and highly metabolic adjacent sites. False positives can occur with active infection, acute inflammation, recent surgical wounds and muscle hypermetabolism. Despite this, with good clinical judgement and with the additional anatomical information provided by the CT scan, PET appears to have a definitive place in the management of lung cancer. In addition to its non-invasive nature, a greater accuracy in staging and possible cost effectiveness [15], it has certainly in our practice not only reduced the number of mediastinal biopsy procedures, but now offers a further advantage with its prognostic value. ✩ Presented at the 13th Annual Meeting of the European Association for Cardio-thoracic Surgery, Glasgow, Scotland, UK, September 5–8, 1999. Appendix A Conference discussion Dr D. Van Raemdonck (Leuven, Belgium): Thank you for this excellent paper. Can you tell us a bit how PET scanning in your institution has changed your attitude towards invasive mediastinal staging? Have you changed your indication for mediastinoscopy or is it still the same as before? Mr Dhital: It has certainly reduced the number of mediastinal biopsies that are being performed. Dr W. Weder (Zurich, Switzerland): You correlated the prognosis with the FDG uptake, but you didn't show us the TNM stage. How was this correlated? Mr Dhital: We have previously reported [2] on the lack of correlation between SUV and tumour stage. While you find a correlation between SUV and tumour size, there does not appear to be a correlation between SUV and staging or histological diagnosis. Dr J. Hasse (Freiburg, Germany): One of the limitations of PET, so far as I know, is the size of tumour or metastasis. What is the critical size when a metastasis or malignant cells can be detected with modern PET facilities? Mr Dhital: In this particular study, the PET resolution was used at 13 mm on CT-positive lesions of 10 mm or more. Dr Hasse: Well, it could be that a small tumour with a high metabolism will be indicated by the PET even if it is only 5 mm of size. Are you informed about the critical size by your PET specialists? Mr Dhital: We use a 13 mm resolution. But, having said that, if the SUV is below 2.5, we accept that to be a benign lesion. Mr K. Jeyasingham (Bristol, UK): You did say that there was no correlation to TNM. But did you in your series have any correlation between the SUV and the cellular differentiation of the tumour itself? That may have a role. Mr Dhital: We haven't looked into that. Mr J. Cockburn (Aberdeen, UK): Can I just ask the audience how many people have access to PET scanning in their practice? (Show of hands) It's quite a high percentage. Cost is one of the problems still, isn't it? Have you any comments on that just before we leave this subject? Mr Dhital: Currently, the cost in our centre is over £700/scan. But that I think can be reduced substantially with gamma counter machines to about a couple of hundred pounds. Hopefully, the prices will keep coming down. References [1] Lowe V.J. , Naunheim K.S. . Current role of positron emission tomography in thoracic oncology , Thorax , 1998 , vol. 53 (pg. 703 - 712 ) Google Scholar Crossref Search ADS PubMed WorldCat [2] Saunders C.A.B. , Dussek J. , O'Doherty M.J. , Maisey M.N. . An evaluation of 18F-FDG whole body PET imaging in the staging of lung cancer , Ann Thorac Surg , 1999 , vol. 67 (pg. 790 - 797 ) Google Scholar Crossref Search ADS PubMed WorldCat [3] Gallagher B.M. , Fowler J.S. , Gutterson N.I. , MacGregor R.R. , Wan C.N. , Wolf A.P. . Metabolic trapping as a principle of radiopharmaceutical design: some factors responsible for the biodistribution of [18F]-2-deoxy-2-fluoro-D-glucose , J Nucl Med , 1978 , vol. 19 (pg. 1154 - 1161 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [4] Minn H. , Zasadny K.R. , Quint C.E. , Wahl R.L. . Lung cancer: reproducibility of quantitative measurements for evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET , Radiology , 1995 , vol. 196 (pg. 167 - 173 ) Google Scholar Crossref Search ADS PubMed WorldCat [5] Duhaylongsod F.G. , Lowe V.J. , Patz E.F. , Vaughan A.L. , Coleman R.E. , Wolfe W.G. . 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Journal

European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: Oct 1, 2000

Keywords: Lung neoplasm Positron emission tomography Surgery Prognosis

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